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BackgroundIn the phase III LUX-Head & Neck 1 (LHN1) trial, afatinib significantly improved progression-free survival (PFS) versus methotrexate in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients progressing on/after platinum-based therapy. This report evaluates afatinib efficacy and safety in prespecified subgroups of patients aged ≥65 and

BACKGROUND: Carotid blowout (CB) represents a dramatic end-of-life situation for palliative head and neck cancer patients, their relatives and caregivers. Recently, endovascular therapy has been proposed for head and neck surgical patients. Preliminary reports showed a better outcome with less morbidity compared to the previous treatment modalities. However, the specific use of such techniques for palliative head and neck cancer patients has not been previously described. METHOD: Retrospective review of two cases of head and neck cancer patients receiving palliative care, presenting with a CB, managed with endovascular stent placement. RESULTS: Bleeding was effectively stopped by the procedure in both cases. Both patients developed a post-procedure thromboembolism, which was immediately treated by appropriate anticoagulation therapy. Neurological symptoms resolved within 24 hours allowing rapid hospital discharge. One patient died at home seven months later. The second patient is alive five months after the procedure. No recurrence of CB occurred in either patient. CONCLUSIONS: Endovascular stent placement for CB allows a rapid arrest of bleeding and permits the use of anticoagulation therapy in order to avoid long-term neurological injury. In our view, carotid stenting should be considered as valid supportive care for palliative head and neck patients presenting with a CB. [ABSTRACT FROM AUTHOR]

Background: To determine the incidence of reversible amenorrhea in women with breast cancer undergoing adjuvant anthracycline-based chemotherapy with or without docetaxel.Methods: We studied the incidence and duration of amenorrhea induced by two chemotherapy regimens: (i) 6 cycles of 5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 on day 1 every 3 weeks (6FEC) and (ii) 3 cycles of FEC 100 followed by 3 cycles of docetaxel 100 mg/m2 on day 1 every 3 weeks (3FEC/3D). Reversible amenorrhea was defined as recovery of regular menses and, where available (101 patients), premenopausal hormone values (luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol) in the year following the end of chemotherapy.Results: One hundred and fifty-four premenopausal patients were included: 84 treated with 6FEC and 70 with 3FEC/3D. The median age was 43.5 years (range: 28-58) in the 6FEC arm and 44 years (range: 29-53) in the 3FEC/3D arm. Seventy-eight percent of patients were treated in the context of the PACS 01 trial. The incidence of chemotherapy-induced amenorrhea at the end of chemotherapy was similar in the two groups: 93 % in the 6FEC arm and 92.8 % in the 3FEC/3D arm. However, in the year following the end of chemotherapy, more patients recovered menses in the 3FEC/3D arm than in the 6FEC arm: 35.5 % versus 23.7 % (p = 0.019). Among the 101 patients for whom hormone values were available, 43 % in the 3FEC/3D arm and 29 % in the 6FEC arm showed premenopausal levels one year after the end of chemotherapy (p < 0.01). In the 3FEC/3D group, there was a statistically significant advantage in disease-free survival (DFS) for patients who were still amenorrheic after one year, compared to patients who had recovered regular menses (p = 0.0017).Conclusion: Our study suggests that 3FEC/3D treatment induces more reversible amenorrhea than 6FEC. The clinical relevance of these findings needs to be investigated further. [ABSTRACT FROM AUTHOR]

Purpose: This multicenter phase Ib study investigated trastuzumab deruxtecan (T-DXd) plus nivolumab in patients with HER2-expressing metastatic breast cancer (mBC) and metastatic urothelial cancer (mUC)., Patients and Methods: Part 1 determined the recommended dose for expansion of T-DXd plus nivolumab. Part 2 evaluated efficacy and safety; the primary endpoint was confirmed objective response rate by independent central review., Results: In part 1, seven patients with mBC were enrolled and received T-DXd 3.2 mg/kg (four patients) or 5.4 mg/kg (three patients) plus nivolumab. The recommended dose for expansion for T-DXd was 5.4 mg/kg plus nivolumab 360 mg intravenously every 3 weeks. In part 2, 32 patients with HER2-positive mBC (cohort 1; inclusive of three administered 5.4 mg/kg in part 1), 16 with HER2-low mBC (cohort 2), 30 with HER2-high mUC (cohort 3), and four with HER2-low mUC (cohort 4) were enrolled. At data cutoff (July 22, 2021), the confirmed objective response rates (95% confidence interval) for cohorts 1 to 4 were 65.6% (46.8%-81.4%), 50.0% (24.7%-75.3%), 36.7% (19.9%-56.1%), and not assessed due to small sample size, respectively. The median treatment duration (range) with T-DXd in cohorts 1 to 4 was 8.9 (1-23) months, 6.9 (1-21) months, 3.9 (1-21) months, and not assessed, respectively; the most common treatment-emergent adverse event was nausea (55.2%, 62.5%, 73.3%, and 75.0%, respectively). Adjudicated drug-related interstitial lung disease/pneumonitis rates (cohorts 1-3) were 20.7%, 0%, and 20.0%, respectively (one grade 5 each, cohorts 1 and 3)., Conclusions: T-DXd plus nivolumab demonstrated promising antitumor activity in HER2-expressing mBC or mUC and safety consistent with the known profile of T-DXd. Interstitial lung disease/pneumonitis is an important risk and requires careful monitoring and prompt intervention., (©2024 The Authors; Published by the American Association for Cancer Research.)

Introduction: Minimal important change estimates (MIC) are useful for interpreting results of clinical research with quality of life (QoL) as an endpoint. For the European Organisation for Research and Treatment of Cancer head and neck cancer module, the EORTC QLQ-HN43, no such thresholds are established., Methods: Head and neck cancer patients under active treatment (n = 503) from 15 countries completed the EORTC QLQ-HN43 three times (t1: before treatment, t2: three months after t1, t3: six months after t1). A subgroup completed a Subjective Significance Questionnaire (SSQ), indicating experienced change from the previous time point in four QoL domains. QoL was assumed to deteriorate after t1 and improve again until t3. The MIC was established using the average of mean differences in SSQ groups (MIC mean ) and estimates based on logistic regressions (MIC predict ). Additionally, minimal detectable changes (MDC) were computed using 0.5 standard deviation and standard error of the mean., Results: For swallowing, speech, dry mouth, and global QoL, the MIC for deterioration were 13, 14, 26, and 10 respectively. The MIC for improvement were 8 (swallowing), 6 (dry mouth), and 5 (global QoL); no MIC for speech improvement can be presented because of insufficient correlation between change score and anchor. The MDC estimates for deterioration were 15, 14, 15, and 11. For improvement, the MDC estimates were 13, 14, 14, and 11., Conclusions: Our results underline that no single MIC or MDC can be applied to all EORTC QLQ-HN43 scales, and that the MIC for deterioration seems larger than those for improvement., Competing Interests: Declaration of Competing Interest Authors declare they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Primary objective was to evaluate the correlation between immune marker expression in baseline tumor biopsies and their respective surgical specimens in squamous cell carcinoma of the oral cavity (OCSCC). Secondary objective was to assess the impact of these markers on overall (OS) and disease-free survival (DFS)., Materials and Methods: Patients with a histological diagnosis of oral squamous cell carcinoma treated surgically between 2012 and 2020 were included in this retrospective, translational monocentric study. The expression of PD-L1, T-cells markers and an OCSCC-adapted immunoscore were evaluated by multiplex immunohistochemistry., Results: One hundred and four patients (mean: 58 years) were included. Seventy patients had paired samples available. Poor correlation was highlighted for PD-L1-positive surface expression (r = 0.29) and combined positive score (CPS). For CPS ≥ 20 and CPS ≥ 1, correlation coefficient r was 0.24 and 0.46 respectively. T-cells density showed also poor correlation with a r of 0.57 and 0.31 for CD3 and CD8 T-cells, respectively. Univariate survival analyses showed significant better OS and DFS (P < 0.05) for patients with stage III-IV OCSCC with a high compared to a low immunoscore, based on surgical samples only., Conclusion: Our study showed poor correlation in PD-L1 expression, CPS, T-cells density and immunoscore between baseline tumor biopsies and surgical resection specimens. In addition, the immunoscore may emerge as a potential prognostic factor in advanced squamous cell carcinoma of the oral cavity. If surgical specimens are available, they may be of interest for clinical practice decision., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JPM reports grants from Boehringer-Ingelheim, Pfizer, Roche, AstraZeneca, Bayer, Innate, Merck Serono, Boehringer, BMS, Novartis, Janssen, Incyte, Cue Biopharma, ALX oncology, iTEOS, eTheRNA, NEKTAR, F-star, Seagen, Genmab, Astellas, CureVac, MSD, Gilead, and Sanofi outside the submitted work. No disclosures were reported by the other authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Despite multimodal therapy, 5-year overall survival for locally advanced head and neck squamous cell carcinoma (HNSCC) is about 50%. We assessed the addition of pembrolizumab to concurrent chemoradiotherapy for locally advanced HNSCC., Methods: In the randomised, double-blind, phase 3 KEYNOTE-412 trial, participants with newly diagnosed, high-risk, unresected locally advanced HNSCC from 130 medical centres globally were randomly assigned (1:1) to pembrolizumab (200 mg) plus chemoradiotherapy or placebo plus chemoradiotherapy. Randomisation was done using an interactive response technology system and was stratified by investigator's choice of radiotherapy regimen, tumour site and p16 status, and disease stage, with participants randomly assigned in blocks of four per stratum. Participants, investigators, and sponsor personnel were masked to treatment assignments. Local pharmacists were aware of assignments to support treatment preparation. Pembrolizumab and placebo were administered intravenously once every 3 weeks for up to 17 doses (one before chemoradiotherapy, two during chemoradiotherapy, 14 as maintenance therapy). Chemoradiotherapy included cisplatin (100 mg/m 2 ) administered intravenously once every 3 weeks for two or three doses and accelerated or standard fractionation radiotherapy (70 Gy delivered in 35 fractions). The primary endpoint was event-free survival analysed in all randomly assigned participants. Safety was analysed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03040999, and is active but not recruiting., Findings: Between April 19, 2017, and May 2, 2019, 804 participants were randomly assigned to the pembrolizumab group (n=402) or the placebo group (n=402). 660 (82%) of 804 participants were male, 144 (18%) were female, and 622 (77%) were White. Median study follow-up was 47·7 months (IQR 42·1-52·3). Median event-free survival was not reached (95% CI 44·7 months-not reached) in the pembrolizumab group and 46·6 months (27·5-not reached) in the placebo group (hazard ratio 0·83 [95% CI 0·68-1·03]; log-rank p=0·043 [significance threshold, p≤0·024]). 367 (92%) of 398 participants treated in the pembrolizumab group and 352 (88%) of 398 participants treated in the placebo group had grade 3 or worse adverse events. The most common grade 3 or worse adverse events were decreased neutrophil count (108 [27%] of 398 participants in the pembrolizumab group vs 100 [25%] of 398 participants in the placebo group), stomatitis (80 [20%] vs 69 [17%]), anaemia (80 [20%] vs 61 [15%]), dysphagia (76 [19%] vs 62 [16%]), and decreased lymphocyte count (76 [19%] vs 81 [20%]). Serious adverse events occurred in 245 (62%) participants in the pembrolizumab group versus 197 (49%) participants in the placebo group, most commonly pneumonia (43 [11%] vs 25 [6%]), acute kidney injury (33 [8%] vs 30 [8%]), and febrile neutropenia (24 [6%] vs seven [2%]). Treatment-related adverse events led to death in four (1%) participants in the pembrolizumab group (one participant each from aspiration pneumonia, end-stage renal disease, pneumonia, and sclerosing cholangitis) and six (2%) participants in the placebo group (three participants from pharyngeal haemorrhage and one participant each from mouth haemorrhage, post-procedural haemorrhage, and sepsis)., Interpretation: Pembrolizumab plus chemoradiotherapy did not significantly improve event-free survival compared with chemoradiotherapy alone in a molecularly unselected, locally advanced HNSCC population. No new safety signals were seen. Locally advanced HNSCC remains a challenging disease that requires better treatment approaches., Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA., Competing Interests: Declaration of interests J-PM, YT, LL, BBu, MTah, DR, GA, IPFL, BGMH, YP, SA, SL, RG, MB, MH, J-PD, RM, MTab, JNW, CS, VG, KJH, and LLS report funding to their institution from Merck Sharp & Dohme (MSD), a subsidiary of Merck & Co, Rahway, NJ, USA to support conduct of this study. J-PM, YT, LL, BBu, MTah, DR, GA, IPFL, BGMH, YP, SA, SL, RG, MB, MH, J-PD, RM, MTab, JNW, CS, VG, KJH, RFS, YZ, BG, BBi, and LLS received medical writing and editorial support for the preparation of this manuscript from MSD. J-PM additionally reports receiving consulting fees managed by the institution for serving as an advisory board member or speaker from Pfizer, Roche, Bayer, Merck Serono, Boehringer, Bristol Myers Squibb (BMS), Novartis, Incyte, Cue Biopharma, ALX Oncology, iTEOS, eTheRNA, NEKTAR, F-Star, Seagen, Genmab, Astellas, CureVac, MSD, GSK, and Merus; receiving travel support managed by the institution from Amgen, BMS, Pfizer, MSD, Gilead, and Sanofi; participating on a data safety monitoring board or advisory board for Psioxus; and serving as the Chair of the EORTC Head and Neck group. YT additionally reports payment or honoraria to themselves from MSD, Merck Serono, and Beigene, and travel support from MSD and Merck Serono. LL additionally reports study funding to their institution from Adlai Nortye, AstraZeneca, BMS, Debiopharm International, Eisai, Eli Lilly and Company, Exelixis, F Hoffman-La Roche, Isa Therapeutics, Kura Oncology, Merck Serono, MSD, Nektar Therapeutics, Novartis, Regeneron, Roche, Sanofi, Syneos, Sun Pharmaceutica, Incyte Biosciences International, Gilead Sciences, Genmab, and Merck Healthcare; consulting fees from MSD IT, Merck Serono Spa Healthcare Professional, Merck Healthcare, GSK, F Hoffman-La Roche, GroupH, ALX Oncology, EMD Serono Research & Development Institute, and Boehringer Ingelheim International; payment or honoraria from Merck Serono Spa, MSD IT, Merck Healthcare, Adlai Nortye, BMS, and ALTIS Omnia Pharma Service; travel support from TAE Life Science; and receiving occasional fees for participation as a speaker at conferences or as a scientific consultant for advisory boards from Merck Healthcare, Neutron Therapeutics, Merck & Co, AstraZeneca, MSD IT, EMD Serono Research & Development Institute, Mirati Therapeutics, F Hoffman-La Roche, Novartis Farma Spa, Janssen Research & Development, Seagen International, Eisai Europe, Genmab US, AstraZeneca UK, and AbbVie. BBu additionally reports participating on an advisory board for and receiving travel support for attending advisory board meetings from MSD. MTah additionally reports honoraria for lectures from MSD and participation on an advisory board for MSD. DR additionally reports study funding to their institution from MSD, GSK, Regeneron, Roche, BMS, Kura, ALX Oncology, Decibel Therapeutics, Eisai, and AstraZeneca and participating on an advisory board (no payment accepted) from MSD, Regeneron, and Sanofi. GA additionally reports receiving grants from MSD, BMS, Merck-Serono, Roche, Pfizer, AstraZeneca, Beigene, Ipsen, and Janssen; serving as an adviser for Merck-Serono and Janssen; and receiving travel support from Janssen. BGMH additionally reports participating on advisory boards for MSD, BMS, Pfizer, AstraZeneca, Eisai, Sanofi, and Takeda. YP additionally reports receiving payment for presenting during a congress symposium from MSD and Merck. SL additionally reports receiving honoraria to the institution for participating on an advisory board from MSD, BMS, and Sanofi Genzyme; receiving travel support to the institution from MSD; and having a pending patent for use of peptides for the vaccination of oropharyngeal cancer (22187930.7-1111). RG additionally reports consulting fees from Celgene, Novartis, Roche, BMS, Takeda, AbbVie, AstraZeneca, Janssen, MSD, Amgen, Merck, Gilead, Daiichi Sankyo, and Sanofi; payment or honoraria from Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, AbbVie, Gilead, Daiichi Sankyo, and Sanofi; travel support from Roche, Amgen, Janssen, AstraZeneca, Novartis, MSD, Celgene, Gilead, BMS, AbbVie, and Daiichi Sankyo; participation on a data safety monitoring board or advisory board for Celgene, Novartis, Roche, BMS, Takeda, AbbVie, AstraZeneca, Janssen, MSD, Amgen, Merck, Gilead, Daiichi Sankyo, and Sanofi; stock or stock options in Novo Nordisk and Lilly; and research funding to the institution from Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, AbbVie, Gilead, and Daiichi Sankyo. MH additionally reports receiving honoraria for lectures from AstraZeneca. JPD additionally reports funding to the institution from AstraZeneca, Amgen, BMS, Genentech, and Transgene; receiving fees to the institution for serving as an invited speaker from Merck Serono; and receiving consulting fees to the institution for serving as an advisory board member from BMS, MSD, Roche-Genentech, and Pierre Fabre. RM additionally reports receiving payment or honoraria from MSD and Merck; receiving travel support from MSD, Merck, Roche, and BMS; and participating on advisory boards for MSD, Merck, Roche, Seagen, Boehringer, Seattle Genetics, Nanobiotix, and Bayer. KJH additionally reports receiving payment in kind to the institution through provision of reagents for experiments on radiation–immunotherapy combinations from AstraZeneca, funding and honoraria to the institution in supports of research on radiation-immunotherapy combinations from Boehringer Ingelheim, consulting fees to the institution from Arch Oncology, AstraZeneca, Boehringer-Ingelheim, Codiak Biosciences, F-start Therapeutics, Inzen Therapeutics, Johnson & Johnson, Merck Serono, MSD, Oncolys Biopharma, Pfizer, Replimmune, and VacV Therapeutics; and payment or honoraria to the institution from Merck Serono, MSD, and Replimmune. RFS additionally reports receiving salary for full-time employment from MSD during part of the time the study was conducted. YZ additionally reports receiving salary for full-time employment from MSD at the time the study was conducted. BG reports holding stock in Merck & Co and receiving salary for full-time employment from MSD. BBi reports holding stock in Merck & Co and receiving salary for full-time employment from MSD. LLS additionally reports receiving funding to the institution to support clinical trials from Novartis, BMS, Pfizer, Boehringer-Ingelheim, GSK, Roche/Genentech, AstraZeneca, Merck, Celgene, Astellas, Bayer, AbbVie, Amgen, Symphogen, Shattucks, BioNTech, 23Me, and EMD Serono; receiving consulting or advisory fees from Merck, Pfizer, AstraZeneca, Roche, GlaxoSmithKline, Voronoi, Arvinas, Tessa, Navire, Relay, Rubius, Daiichi Sankyo, Coherus, Marengo, InteRNA, Tubulis, LTZ Therapeutics, and NGM Biotherapeutics; participating on a data safety monitoring board or advisory board without compensation for Mirati Therapeutics; and reports that their spouse owns stock in Agios; and is a cofounder of Treadwell Therapeutics., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Safety and efficacy of acapatamab, a prostate-specific membrane antigen (PSMA) x CD3 bispecific T-cell engager were evaluated in a first-in-human study in metastatic castration-resistant prostate cancer (mCRPC)., Patients and Methods: Patients with mCRPC refractory to androgen receptor pathway inhibitor therapy and taxane-based chemotherapy received target acapatamab doses ranging from 0.003 to 0.9 mg in dose exploration (seven dose levels) and 0.3 mg (recommended phase II dose) in dose expansion intravenously every 2 weeks. Safety (primary objective), pharmacokinetics, and antitumor activity (secondary objectives) were assessed., Results: In all, 133 patients (dose exploration, n = 77; dose expansion, n = 56) received acapatamab. Cytokine release syndrome (CRS) was the most common treatment-emergent adverse event seen in 97.4% and 98.2% of patients in dose exploration and dose expansion, respectively; grade ≥ 3 was seen in 23.4% and 16.1%, respectively. Most CRS events were seen in treatment cycle 1; incidence and severity decreased at/beyond cycle 2. In dose expansion, confirmed prostate-specific antigen (PSA) responses (PSA50) were seen in 30.4% of patients and radiographic partial responses in 7.4% (Response Evaluation Criteria in Solid Tumors 1.1). Median PSA progression-free survival (PFS) was 3.3 months [95% confidence interval (CI): 3.0-4.9], radiographic PFS per Prostate Cancer Clinical Trials Working Group 3 was 3.7 months (95% CI: 2.0-5.4). Acapatamab induced T-cell activation and increased cytokine production several-fold within 24 hours of initiation. Treatment-emergent antidrug antibodies were detected in 55% and impacted serum exposures in 36% of patients in dose expansion., Conclusions: Acapatamab was safe and tolerated and had a manageable CRS profile. Preliminary signs of efficacy with limited durable antitumor activity were observed. Acapatamab demonstrated pharmacokinetic and pharmacodynamic activity., (©2024 American Association for Cancer Research.)

Background: Selective biomarkers may improve outcomes in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitor therapy. We investigated three independent biomarkers for association with efficacy in the randomized, phase III KESTREL study (NCT02551159) of first-line durvalumab monotherapy or durvalumab plus tremelimumab versus the EXTREME regimen: programmed cell death ligand-1 (PD-L1) immunohistochemistry, blood tumor mutational burden (bTMB) via circulating tumor DNA, and neutrophil-to-lymphocyte ratio (NLR)., Methods: Tumor or blood samples from patients enrolled in the KESTREL study were analyzed for PD-L1, bTMB, and NLR. Associations with overall survival (OS) or objective response rates (ORRs) were evaluated based on prespecified cut-offs for PD-L1 (tumor cell [TC] ≥ 50%/immune cell ≥ 25% or TC ≥ 25%), bTMB (≥ 16 mutations [mut] per megabase [Mb]), and NLR (≤ 7). Ad hoc analyses of exploratory cut-offs were performed., Results: Prespecified or exploratory cut-offs for PD-L1 did not enrich for ORR or OS for durvalumab monotherapy or durvalumab plus tremelimumab versus EXTREME. In the bTMB ≥ 16 mut/Mb subgroup, OS hazard ratios (95% confidence interval) for durvalumab monotherapy and durvalumab plus tremelimumab versus EXTREME were 0.90 (0.48-1.72) and 0.69 (0.39-1.25), respectively. Complete response rates were 8.6% with durvalumab plus tremelimumab and 4.3% with EXTREME (≥ 16 mut/Mb subgroup). No improvement in OS was observed for durvalumab monotherapy or durvalumab plus tremelimumab versus EXTREME at prespecified or exploratory NLR cut-offs., Conclusions: bTMB demonstrated potential utility for selecting patients with R/M HNSCC who benefited from durvalumab with or without tremelimumab versus EXTREME. Trial registration ClinicalTrials.gov identifier NCT02551159., (© 2024. The Author(s).)

Background: Only 15-20% of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) patients derive long-term benefit from nivolumab or pembrolizumab. We developed a circulating tumour DNA (ctDNA) tumour-agnostic assay aimed at the early prediction of single agent programmed cell death 1 (PD1) inhibitor efficacy in R/M SCCHN., Patients and Methods: Our tumour-agnostic assay included 37 genes frequently mutated in R/M SCCHN and two HPV16 genes. Primary endpoint was the concordance between ctDNA kinetics (ΔctDNA) and the best overall response according to Response Evaluation Criteria in Solid Tumors version 1.1. ΔctDNA was defined as the difference in mean variant allele frequency (VAF) between the on-treatment sample harvested 6-10 weeks (FU1) after PD1 inhibitor initiation and the pre-treatment plasma sample (ΔctDNA = mean FU1 VAF - mean pre-treatment VAF)., Results: ctDNA was detected in 35/44 (80%) of the pre-treatment plasma samples. The concordance between ΔctDNA and imaging response was observed in 74%. Median progression-free survival was 8.6 months in the favourable ΔctDNA group and 2.5 months in the unfavourable ΔctDNA group (p = 0.057). Median overall survival (OS) was 18.1 and 8.2 months in the favourable and unfavourable ΔctDNA groups, respectively (p = 0.13). In patients with PD-L1 expressing SCCHN (Combined Positive Score ≥1), OS was significantly better in patients with favourable ΔctDNA compared with patients with unfavourable ΔctDNA: median OS was 41.5 and 8.4 months (p = 0.033), respectively., Conclusions: Tumour-agnostic ctDNA analysis for human papillomavirus (HPV)-negative and HPV-positive R/M SCCHN is feasible. ctDNA kinetics show promising results in predicting the efficacy of PD1 inhibitors in R/M SCCHN., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Forty to fifty percent of patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) relapse despite multimodal treatment. Circulating tumor DNA (ctDNA) has the potential to detect minimal residual disease (MRD) after curative-intent therapy and to identify earlier which patients will progress. We developed a tumor-agnostic plasma ctDNA assay to detect MRD in unselected LA SCCHN with the aim of predicting progression-free survival (PFS) and overall survival without the need for tumor sequencing., Patients and Methods: A 26-gene next-generation sequencing panel was constructed that included the most frequently mutated genes in SCCHN and two HPV-16 genes. MRD was assessed in each patient through an in-house informatic workflow informed by somatic mutations identified in the corresponding pre-treatment plasma sample. The presence of MRD was defined as the detection of ctDNA in one plasma sample collected within 1-12 weeks of the end of curative treatment. The primary endpoint was the PFS rate at 2 years. At least 32 patients were planned for inclusion with the hypothesis that PFS at 2 years was >80% in MRD-negative patients and <30% in MRD-positive patients (α = 0.05, β = 0.9)., Results: We sequenced DNA from 116 plasma samples derived from 53 LA SCCHN patients who underwent curative-intent treatment. ctDNA was detected in 41/53 (77%) patients in the pre-treatment samples. Out of these 41 patients, 17 (41%) were MRD positive after treatment. The 2-year PFS rate was 23.53% (9.9% to 55.4%) and 86.6% (73.4% to 100%) in MRD-positive and MRD-negative patients, respectively (P < 0.05). Median survival was 28.37 months (14.30 months-not estimable) for MRD-positive patients and was not reached for the MRD-negative cohort (P = 0.011)., Conclusions: Our ctDNA assay detects MRD in LA SCCHN and predicts disease progression and survival without the need for tumor sequencing, making this approach easily applicable in daily practice., (Copyright © 2023 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Background: In the phase 3 KEYNOTE-040 study, pembrolizumab prolonged OS versus chemotherapy in previously treated recurrent or metastatic (R/M) HNSCC. We present a post hoc subgroup analysis by disease recurrence pattern: recurrent-only, recurrent and metastatic (recurrent-metastatic), and metastatic-only HNSCC., Materials and Methods: Patients had HNSCC that progressed during or after platinum-containing treatment for R/M disease or had recurrence or progression within 3-6 months of previous platinum-containing definitive therapy for locally advanced disease. Patients were randomly assigned (1:1) to pembrolizumab 200 mg Q3W or investigator's choice of standards of care (SOC): methotrexate, docetaxel, or cetuximab. Outcomes included OS, PFS, ORR, and DOR. The data cutoff was May 15, 2017., Results: There were 125 patients (pembrolizumab, 53; SOC, 72) in the recurrent-only subgroup, 204 in the recurrent-metastatic subgroup (pembrolizumab, 108; SOC, 96), and 166 in the metastatic-only subgroup (pembrolizumab, 86; SOC, 80). The hazard ratio (95% CI) for death for pembrolizumab versus SOC was 0.83 (0.55-1.25) in the recurrent-only, 0.78 (0.58-1.06) in the recurrent-metastatic, and 0.74 (0.52-1.05) in the metastatic-only subgroups. PFS was similar between treatment arms in all subgroups. ORR was 22.6% for pembrolizumab versus 16.7% for SOC in the recurrent-only, 10.2% versus 6.3% in the recurrent-metastatic, and 15.1% versus 8.8% in the metastatic-only subgroups. DOR was numerically longer with pembrolizumab in all subgroups., Conclusion: Pembrolizumab provided numerically longer OS and durable responses in all subgroups compared with SOC, suggesting that patients with previously treated R/M HNSCC benefit from pembrolizumab regardless of recurrence pattern., Competing Interests: Declaration of Competing Interest KJH reports honoraria from BMS, Merck-Serono, MSD, and Replimune; advisory/consultancy roles with Arch Oncology, AstraZeneca, BMS, Boehringer-Ingelheim, Codiak, Eisai, Inzen, Merck-Serono, MSD, Oncolys, Pfizer, and Replimune; speaker bureau for BMS, Merck-Serono, MSD, and Replimune; and research grant/funding from AstraZeneca, Boehringer-Ingelheim, and Replimune. EEWC reports advisory/consultancy roles with Axelia, Cel Sci, Eisai, Hoopika, ImmunoSensor, Istari, Janssen, Kahr Medical, Mana Therapeutics, Merck, Mirati, MSD, Nectin Tx, Pangea Therapeutics, and Roche; is a member of the board of directors for Psiouxus Therapeutics, and NCCN; has stock/shares with Kinnate Biopharma and Primmune Therapeutics; and has a leadership role with Ayala, Kura, and Kinnate Biopharma DS reports advisory/consultancy roles with Merck and Adlai-Nortye and research grant/funding from Merck, GSK, Adlai-Nortye, and BMS. JD reports advisory/consultancy role with Roche, PharmaMar, BMS, Merck Serono, and MSD; is a principal investigator for studies from Roche, BI, and MSD; and travel expenses from PharmaMar. LL reports research funding from Astrazeneca, BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis, Debiopharm International SA, Hoffmann-La Roche ltd, IRX Therapeutics, Medpace, Merck-Serono, MSD, Novartis, Pfizer, Roche, and Buran; and occasional fees for participation as a speaker at conferences/congresses or as a scientific consultant for advisory boards from Astrazeneca, Bayer, MSD, Merck-Serono, AccMed, and Neutron Therapeutics, Inc. MJA reports honoraria from AstraZeneca, Lilly, MSD, Merck, TAKEDA, ONO, Amgen, YUHAN, and Roche; advisory/consultancy roles with AstraZeneca, Lilly, MSD, Merck, TAKEDA, ONO, Amgen, YUHAN, Roche, and Alpha Pharmaceuticals; and research grant/funding from YUHAN. AS reports honoraria from MSD, Merck Serono, Novartis Pharma, Bristol Myers Squibb, Pierre Fabre, and Sanofi; and advisory/consultancy roles with MSD, Merck Serono, Novartis Pharma, Bristol Myers Squibb, Pierre Fabre, and Sanofi. JPM reports advisory/consultancy roles with Pfizer, Roche, AstraZeneca, Bayer, Innate, Merck Serono, Boerhinger, BMS, Novartis, Janssen, Incyte, Cue Biopharma, ALX Oncology, iTEOS, eTheRNA, NEKTAR, F-Star, Seagen, Genmab, Astellas, and Psioxius; leadership roles with the EORTC head and neck group (Chair); travel/accommodation/expenses from Amgen, BMS, Pfizer, MSD, and Gilead; and non-remunerated activities with MSD (Advisory board). NM reports being a co-founder and shareholder MaxiVAX, a personalized cancer immunotherapy biotech, with ongoing Phase IIa in patients with advanced Head & Neck cancer; and being the Chief Medical Officer at MaxiVAX. RM reports advisor/consultancy role for Janssen, AstraZeneca (uncompensated), Coherus and Rakuten Medical; and research funding from Merck. BB reports advisory/consultancy roles with Genentech, Glaxo Smith Kline, Nektar, Debio, Merck KgA, Astra Zeneca,Vaccinex, Exelexis, Cue BioPharma, Fusion, Arvinas, Coherus, ALX Oncology, Hookipa Kura, Astra Zeneca/Medimmune, Nektar, and Roche; and research grant/funding from Cue Biopharma, Merck, Gilead, Exelexis, and Vaccinex. RFS reports employment at the time of the study at Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; current employment at Carisma Therapeutics. JL reports employment at Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and stock ownership in Merck & Co., Inc., Rahway, NJ, USA. JG reports employment at Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and stock ownership in Merck & Co., Inc., Rahway, NJ, USA. NL reports employment at Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and stock ownership in Merck & Co., Inc., Rahway, NJ, USA. CLT reports honoraria from MSD, BMS, Merck Serono, Celgene, Astra Zeneca, Seattle Genetics, Maxivax, Seagen, and Roche; research grant/funding from MSD; and travel/accommodation/expenses from MSD, Merck Serono, Astra Zeneca, and BMS., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: During the first wave of the COVID-19 pandemic in 2020, non-essential health services were suspended in Belgium, and the public was ordered to socially isolate. Underdiagnosis of cancer during this period was reported worldwide. Certain risk factors for head and neck cancer (HNC) overlap with those for COVID-19 incidence and mortality, making underdiagnosis and subsequent stage shift of this potentially rapidly progressing cancer a major concern. We aimed to analyze incidence, clinical stage at presentation, and survival of patients diagnosed with HNC in 2020 in Belgium, considering recent temporal trends., Methods: Using population-based data from the Belgian Cancer Registry (BCR), we extrapolated 2017-2019 trends in incidence, clinical stage, and 1-year relative survival (1yRS) of HNC to create an expected value for 2020 and compared this to the observed value., Results: There were 9.5% fewer HNCs diagnosed in 2020, compared to the predicted incidence. Underdiagnosis was larger for males (-11.8%), patients aged 50-64 (-11.2%) and 65-79 (-11.1%), and for oral cavity cancer (-17.6%). Shifts to more advanced stages were observed in larynx and oropharynx tumors and for (male) patients aged 80+. A 2.4 percentage point decline in 1yRS was observed, relative to the increasing trends in 1yRS (2017-2019)., Conclusion: The COVID-19 pandemic led to underdiagnosis of HNC, resulting in shifts to more advanced stage at presentation in certain subgroups. A stage shift can be expected for the 9.5% of tumors not yet diagnosed at the end of 2020. HNC patients diagnosed in 2020 suffered higher than expected mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Peacock, De Gendt, Silversmit, Nuyts, Casselman, Machiels, Giusti, van Gool, Vander Poorten and Van Eycken.)

Background: Bromodomain and extraterminal domain (BET) inhibitors have demonstrated efficacy in solid tumours and haematological malignancies. BI 894999 is a novel oral BET inhibitor that has demonstrated potent antitumour activity in preclinical studies., Patients and Methods: 1367.1 was an open-label, Phase Ia/Ib dose-finding study evaluating BI 894999 once daily in patients with advanced solid tumours (Schedule A: 0.2, 0.5, 1.0, 1.5, 2.0, and 5.0 mg, Days 1-21/21-d cycle; Schedule B: 1.5, 2.0, and 2.5 mg, Days 1-15/21-d cycle; Schedule C: loading dose 5.0, 6.0, or 7.0 mg on Day 1 followed by maintenance dose 2.5, 3.0, or 3.5 mg, Days 2-7 and 15-21/28-d cycle); 77 patients were enrolled. NCT02516553., Results: Grade ≥3 dose-limiting toxicities (DLTs) were reported in 8/21, 5/25, and 9/31 patients for Schedules A, B, and C, respectively. Thrombocytopenia was reported as a DLT in 28.6%, 4.8%, and 9.7% for Schedules A, B, and C, respectively. Other DLTs occurring in ≥1 patient were troponin T increase (13.6%), hypophosphataemia (4.5%), and elevated creatine phosphokinase (3.0%). Disease control was achieved in 23.8%, 24.0%, and 29.0% of patients for Schedules A, B, and C, respectively. A partial response was achieved in 9.5% and 4% of patients with Schedules A and B, respectively. The best response with Schedule C was stable disease., Conclusion: The 1.5, 2.5, and 6.0/3.0 mg doses in Schedules A, B, and C, respectively, were declared as maximum tolerated dose. Based on the strength of these data, BI 894999 was further evaluated in a Phase Ib trial., Competing Interests: Declaration of Competing Interest Patrick Schöffski declares institutional translational research funding for work; an ongoing advisory function; receiving personal honoraria; travel support to attend BET inhibitor-related advisory functions; personal honoraria for educational activities outside of the scope of this paper from Boehringer Ingelheim; consulted/advised for Deciphera, Ellipses Pharma, Blueprint Medicines, Transgene, Exelixis, Studiecentrum voor Kernenergie, SQZ Biotechnology, Adcendo, PharmaMar, Merck Healthcare KGaA, Medpace; and received research support from CoBioRes NV, Eisai, G1 Therapeutics, PharmaMar, Genmab, Merck, Sartar Therapeutics, and ONA Therapeutics. Jean-Pascal Machiels has consulted/advised for ALX Oncology, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CUE Biopharma, Debiopharm, Incyte Corporation, Innate Pharma, Janssen, Merck Serono, Merck Sharp & Dohme, Nanobiotix, Novartis, Pfizer, Roche; received research funding from Bayer, Janssen, Novartis, Sanofi; and travel, accommodations, and expenses from Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, and Pfizer. Sylvie Rottey has received travel grants and advisory/speaker fees from Novartis, Roche, Pfizer, MSD, Bristol Myers Squibb, Ipsen; and received research grants from Roche, MSD. Behbood Sadrolhefazi and Kristell Marzin are employees of Boehringer Ingelheim. Hanny Musa is a former employee of Boehringer Ingelheim. Ahmad Awada has received advisory and speaker fees from Amgen, AstraZeneca, Bayer, Daiichi, EISAI, Genomic Health, Ipsen, LEO Pharma, Lilly, Merck, MSD, Novartis, Pfizer, and Seattle Genetics; received advisory fees from Hengrui, Innate, and Viatris; and received research grants from Bristol Myers Squibb and Roche., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: To build and externally validate an [ 18 F]FDG PET radiomic model to predict overall survival in patients with head and neck squamous cell carcinoma (HNSCC)., Methods: Two multicentre datasets of patients with operable HNSCC treated with preoperative afatinib who underwent a baseline and evaluation [ 18 F]FDG PET/CT scan were included (EORTC: n = 20, Unicancer: n = 34). Tumours were delineated, and radiomic features were extracted. Each cohort served once as a training and once as an external validation set for the prediction of overall survival. Supervised feature selection was performed using variable hunting with variable importance, selecting the top two features. A Cox proportional hazards regression model using selected radiomic features and clinical characteristics was fitted on the training dataset and validated in the external validation set. Model performances are expressed by the concordance index (C-index)., Results: In both models, the radiomic model surpassed the clinical model with validation C-indices of 0.69 and 0.79 vs. 0.60 and 0.67, respectively. The model that combined the radiomic features and clinical variables performed best, with validation C-indices of 0.71 and 0.82., Conclusion: Although assessed in two small but independent cohorts, an [ 18 F]FDG-PET radiomic signature based on the evaluation scan seems promising for the prediction of overall survival for HNSSC treated with preoperative afatinib. The robustness and clinical applicability of this radiomic signature should be assessed in a larger cohort.

Background: Talazoparib has shown antitumor activity with a manageable safety profile in men with metastatic castration-resistant prostate cancer (mCRPC) and DNA damage response (DDR)/homologous recombination repair (HRR) alterations., Objective: To evaluate patient-reported health-related quality of life (HRQoL) and pain in patients who received talazoparib in the TALAPRO-1 study, with a special interest in patients harboring breast cancer susceptibility gene 1 or 2 (BRCA1/2) mutations., Design, Setting, and Participants: TALAPRO-1 is a single-arm, phase 2 study in men with mCRPC DDR alterations either directly or indirectly involved in HRR, who previously received one to two taxane-based chemotherapy regimens for advanced prostate cancer and whose mCRPC progressed on one or more novel hormonal agents., Outcome Measurements and Statistical Analysis: Men completed the European Quality-of-life Five-dimension Five-level scale (EQ-5D-5L), EQ-5D visual analog scale (VAS), and Brief Pain Inventory-Short Form at predefined time points during the study. The patient-reported outcome (PRO) population included men who completed a baseline and one or more postbaseline assessments before study end. Longitudinal mixed-effect models assuming an unstructured covariance matrix were used to estimate the mean (95% confidence interval [CI]) change from baseline for pain and general health status measurements among all patients and patients with BRCA1/2 mutations., Results and Limitations: In the 97 men in the PRO population treated with talazoparib (BRCA1/2, n = 56), the mean (95% CI) EQ-5D-5L Index improved (all patients, 0.05 [0.01, 0.08]; BRCA1/2 subset, 0.07 [0.03, 0.10]), as did the EQ-5D VAS scores (all patients, 5.42 [2.65, 8.18]; BRCA1/2 subset, 4.74 [1.07, 8.41]). Improvements in the estimated overall change from baseline (95% CI) in the mean worst pain were observed in all patients (-1.08 [-1.52, -0.65]) and the BRCA1/2 subset (-1.15 [-1.67, -0.62]). The probability of not having had experienced deterioration of worst pain by month 12 was 84% for all patients and 83% for the BRCA1/2 subset., Conclusions: In heavily pretreated men with mCRPC and DDR/HRR alterations, talazoparib was associated with improved HRQoL in all patients and the BRCA1/2 subset. In both patient groups, worst pain improved from baseline and the probability of not experiencing a deterioration in worst pain with talazoparib was high., Patient Summary: We show that talazoparib was associated at least with no change or improvements in health-related quality of life (HRQoL) and pain burden in men with metastatic castration-resistant prostate cancer and DNA damage response/homologous recombination repair gene alterations in the TALAPRO-1 study. These findings in patient-reported HRQoL and pain complement the antitumor activity and tolerability profile of talazoparib., (Copyright © 2022 The Pfizer, The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Fibroblast growth factor receptor (FGFR)-4/FGF19 pathway dysregulation is implicated in hepatobiliary and other solid tumors. INCB062079, an oral, selective, FGFR4 inhibitor, inhibits growth in FGF19/FGFR4-driven liver cancer models., Methods: This was a two-part, phase I study (NCT03144661) in previously treated patients with advanced solid tumors. The primary objective was to determine safety, tolerability, and maximum tolerated dose (MTD), while secondary objectives included pharmacokinetics, pharmacodynamics (plasma FGF19; bile acid salts/7α-hydroxy-4-cholesten-3-one [C4] levels), and preliminary efficacy. In Part 1, patients received INCB062079 starting at 10 mg once daily, with 3 + 3 dose escalation. Part 2 (dose expansion) was not conducted because of study termination., Results: Twenty-three patients were treated (hepatobiliary, n = 11; ovarian, n = 9; other, n = 3). Among six patients receiving 15 mg twice daily, two patients had dose-limiting toxicities (DLTs; grade 3 diarrhea, grade 3 transaminitis). Both had high pretreatment C4 concentrations, prompting a protocol amendment requiring pretreatment C4 concentrations < 40.9 ng/mL and concomitant prophylactic bile acid sequestrant treatment. No additional DLTs were reported at 10 and 15 mg twice daily; higher doses were not assessed. The most common toxicity was diarrhea (60.9%). INCB062079 exposure was dose-proportional; FGF19 and bile acid/C4 concentrations increased with exposure. One partial response was achieved (15 mg twice daily; ovarian cancer; FGF/FGFR status unknown; duration of response, 7.5 months); two patients had stable disease., Conclusions: With C4 cut-off and prophylactic bile acid sequestrant implementation, INCB062079 demonstrated a manageable safety profile and evidence of target inhibition. In view of the rarity of FGF19/FGFR4 alterations and slow patient accrual, the study was terminated before establishing an MTD., (© 2023. The Author(s).)

Background: Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis. The phase III KESTREL study evaluated the efficacy of durvalumab [programmed death-ligand 1 (PD-L1) antibody] with or without tremelimumab [cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody], versus the EXTREME regimen in patients with R/M HNSCC., Patients and Methods: Patients with HNSCC who had not received prior systemic treatment for R/M disease were randomized (2 : 1 : 1) to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W (up to four doses), durvalumab monotherapy 1500 mg Q4W, or the EXTREME regimen (platinum, 5-fluorouracil, and cetuximab) until disease progression. Durvalumab efficacy, with or without tremelimumab, versus the EXTREME regimen in patients with PD-L1-high tumors and in all randomized patients was assessed. Safety was also assessed., Results: Durvalumab and durvalumab plus tremelimumab were not superior to EXTREME for overall survival (OS) in patients with PD-L1-high expression [median, 10.9 and 11.2 versus 10.9 months, respectively; hazard ratio (HR) = 0.96; 95% confidence interval (CI) 0.69-1.32; P = 0.787 and HR = 1.05; 95% CI 0.80-1.39, respectively]. Durvalumab and durvalumab plus tremelimumab prolonged duration of response versus EXTREME (49.3% and 48.1% versus 9.8% of patients remaining in response at 12 months), correlating with long-term OS for responding patients; however, median progression-free survival was longer with EXTREME (2.8 and 2.8 versus 5.4 months). Exploratory analyses suggested that subsequent immunotherapy use by 24.3% of patients in the EXTREME regimen arm contributed to the similar OS outcomes between arms. Grade 3/4 treatment-related adverse events (TRAEs) for durvalumab, durvalumab plus tremelimumab, and EXTREME were 8.9%, 19.1%, and 53.1%, respectively., Conclusions: In patients with PD-L1-high expression, OS was comparable between durvalumab and the EXTREME regimen. Durvalumab alone, and with tremelimumab, demonstrated durable responses and reduced TRAEs versus the EXTREME regimen in R/M HNSCC., Competing Interests: Disclosure AP has received research funding from Bristol Myers Squibb, DEMO, KURA Oncology, and Roche and consultant/advisory/honoraria fees from AstraZeneca, Bristol Myers Squibb, HPVtRNA, Merck Serono, MSD, Nanobiotics, and Pfizer companies. JF has served in a consulting or advisory role for Bristol Myers Squibb, Innate Pharma, Merck, Merck Sharp & Dohme, Rakuten, and Roche and has received non-financial support from Bristol Myers Squibb and Merck Sharp & Dohme. KH has received research funding from AstraZeneca, Boehringer Ingelheim, MSD, and Replimune, and consultant/advisory/honoraria fees from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Codiak, Inzen, Merck Serono, Mersana Therapeutics, MSD, Pfizer, and Replimune. MG has received research funding from Agenus, Bristol Myers Squibb, Cullinan Labs, Genentech, Genocea Biosciences Inc., Kura, LaRoche, NRG, and University of Cincinnati. She has received consulting fees from Amgen Inc., Aspyrian Therapeutics, AstraZeneca Pharmaceuticals, Bayer Healthcare Pharmaceutics, Bicara Therapeutics, Bicara, BioNtech AG, Bristol Myers Squibb, Celgene Corp, Coherus Biosciences, Debiopharm, Eisai Medical Research Inc., EMD Serono, Inc., Genocea Biosciences Inc., Gilead Sciences Inc., Ipsen Biopharmaceuticals Inc., Istari Oncology Inc., iTeos Therapeutics, Kura Oncology, LLX Solutions, LLC, Merck & Co, Mirati Therapeutics, Nektar Therapeutics, NewLink Genetics Corp., OncLive Intellisphere, Roche Diagnostics GmbH, Roche, Seagen, Sensei Biotherapeutics Inc., Shattuck Labs Inc., and TRM Oncology. She received honoraria from OncLive and Roche. She has received support for attending meetings and/or travel from AACR, ASCO, and SITC. She reports an issued patent for NGVL4a-Sig/E7(detox)/HSP70 plasmid DNA for a clinical protocol entitled ‘An open-label phase one study of the safety with stage III or IV HPV16-positive head and neck squamous cell carcinoma’ and pending patents for oral HPV infection detection for oral cancer screening and diagnosis, and for HPV mRNA detection on oral cytology specimens for diagnosis and screening for oral cancer. She reports participation on a data safety monitoring board or advisory board for BioMimetix, Kura, NRG, Seagen, Sensei Biotherapeutics Inc., and SQZBiotech. She reports stock options with Sensei. MJA has received honoraria from AstraZeneca, Bristol Myers Squibb, MSD, ONO, and Roche and is a consultant or advisor for AstraZeneca, Bristol Myers Squibb, Takeda, MSD, Novartis, Roche, and Alpha pharmaceutical. ST reports grants from AstraZeneca, during the conduct of the study; grants and personal fees from Eisai, Novartis, Taiho, MSD, Chugai, Bayer, and Daiichi-Sankyo, outside the submitted work. JW has stock and other ownership interests in Achilles Therapeutics, Nektar Therapeutics, Vesselon, Nuvalent, En Fuego Therapeutics, and Lyell Immunopharma. He has a consulting or advisory role with AstraZeneca, EMD Serono, Genentech, G1 Therapeutics, Jounce Therapeutics, AbbVie, Nanobiotix, Azitra, Eli Lilly, Blueprint Medicines, Pfizer, Saatchi Wellness, Jazz Pharmaceuticals, Boehringer Ingelheim, Regeneron, Genmab, SDP Oncology, and BeiGene. He has received research funding from Mirati Therapeutics, Sumitomo Dainippon Pharma Oncology, Boehringer Ingelheim, and PDS Biotechnology. His institution has received research funding from Amgen, G1 Therapeutics, Immunicum, Inspirna, and Loxo/Lilly. He has had travel, accommodations, or expenses paid by Mirati Therapeutics. JPM is an advisory board member or speaker with honoraria (institution managed) for: Pfizer, Roche, AstraZeneca, Bayer, Innate, Merck Serono, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Janssen, Incyte, Cue Biopharma, ALX Oncology, iTEOS, eTheRNA, and Nektar Therapeutics. He has accepted travel expenses from: Amgen, Bristol Myers Squibb, Pfizer, and MSD. He is on the data safety monitoring board with honoraria for Psioxus. His institutional conflict of interest (funding to institution for research support) includes all companies. He has an uncompensated advisory role with MSD. SB reports owning stock in Roche Holding AG and is an employee of Verana Health. SCT reports receiving grant or research support from AstraZeneca and Eisai and consultant fees from AstraZeneca. RH is an employee of Dana-Farber Cancer Institute and has a leadership role with NCCN. He is a consultant or advisor for Achilles Therapeutics, AstraZeneca, Bayer, BioNTech AG, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Coherus Biosciences, Eisai, EMD Serono, Genentech, Gilead Sciences, GSK, Immunomic Therapeutics, Loxo, Merck, MIRATI, Pfizer, and Vaccinex. His institution has received research funding from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Genentech, Kura, Merck, and Pfizer. He has other relationships with ISA Pharmaceuticals and Nanobiotix. SK received honoraria from Merck Serono, MSD, Novartis, Bristol Myers Squibb, Amgen, Roche, Sanofi-Aventis, Servier, Incyte, and Lilly; research funding from Merck Serono, Lilly, Bristol Myers Squibb, and Roche. PSM received advisory/lecture honoraria from BMS, KLS Martin Group, and Roche. He has accepted travel expenses from: AstraZeneca, BMS, GSK, KLS Martin Group, MSD, and Roche. VB is a freelance contractor for, and shareholder in, AstraZeneca. PH, BE, SW, RFO, AY, JFK, and NM are or were employees and shareholders of AstraZeneca. SW and NM report published patent WO2021228988A1. TYS has received grants/research funding from AstraZeneca, Bristol Myers Squibb, CUE biopharma, Kura, Merck/MSD, Nanobiotix, Regeneron, and Roche/Genentech, as well as honoraria from Bayer, BioNTech/Syneos, Coherur Biosciences, Cue Biopharma, Innate, KURA, Merck/MSD, Nanobiotix, Sanofi, Vir Biotechnology. All other authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: CYAD-01 is an autologous chimeric antigen receptor (CAR) T-cell product based on the natural killer (NK) group 2D (NKG2D) receptor, which binds eight ligands that are overexpressed in a wide range of haematological malignancies but are largely absent on non-neoplastic cells. Initial clinical evaluation of a single infusion of CYAD-01 at a low dose in patients with relapsed or refractory acute myeloid leukaemia, myelodysplastic syndromes, and multiple myeloma supported the feasibility of the approach and prompted further evaluation of CYAD-01. The aim of the present study was to determine the safety and recommended phase 2 dosing of CYAD-01 administered without preconditioning or bridging chemotherapy., Methods: The multicentre THINK study was an open-label, dose-escalation, phase 1 study for patients with relapsed or refractory acute myeloid leukaemia, myelodysplastic syndromes, or multiple myeloma, after at least one previous line of therapy. Patients were recruited from five hospitals in the USA and Belgium. The dose-escalation segment evaluated three dose levels: 3 × 10 8 (dose level one), 1 × 10 9 (dose level two), and 3 × 10 9 (dose level three) cells per infusion with a 3 + 3 Fibonacci study design using a schedule of three infusions at 2-week intervals followed by potential consolidation treatment consisting of three additional infusions. The occurrence of dose-limiting toxicities post-CYAD-01 infusion was assessed as the primary endpoint in the total treated patient population. The trial was registered with ClinicalTrials.gov, NCT03018405, and EudraCT, 2016-003312-12, and has been completed., Findings: Between Feb 6, 2017, and Oct 9, 2018, 25 patients were registered in the haematological dose-escalation segment. Seven patients had manufacturing failure for insufficient yield and two had screening failure. 16 patients were treated with CYAD-01 (three with multiple myeloma and three with acute myeloid leukaemia at dose level one; three with acute myeloid leukaemia at dose level two; and six with acute myeloid leukaemia and one with myelodysplastic syndromes at dose level three). Median follow-up was 118 days (IQR 46-180). Seven patients (44%) had grade 3 or 4 treatment-related adverse events. In total, five patients (31%) had grade 3 or 4 cytokine release syndrome across all dose levels. One dose-limiting toxicity of cytokine release syndrome was reported at dose level three. No treatment-related deaths occurred, and the maximum tolerated dose was not reached. Three (25%) of 12 evaluable patients with relapsed or refractory acute myeloid leukaemia or myelodysplastic syndromes had an objective response. Among responders, two patients with acute myeloid leukaemia proceeded to allogeneic haematopoietic stem-cell transplantation (HSCT) after CYAD-01 treatment, with durable ongoing remissions (5 and 61 months)., Interpretation: Treatment with a multiple CYAD-01 infusion schedule without preconditioning is well tolerated and shows anti-leukaemic activity, although without durability outside of patients bridged to allogeneic HSCT. These phase 1 data support the proof-of-concept of targeting NKG2D ligands by CAR T-cell therapy. Further clinical studies with NKG2D-based CAR T-cells are warranted, potentially via combinatorial antigen targeted approaches, to improve anti-tumour activity., Funding: Celyad Oncology., Competing Interests: Declaration of interests DAS has received payment as a member of advisory boards for Aprea, AvenCell, BlueBird Bio, Bristol Myers Squibb (BMS), Intellia, Kite, Novartis, Shattuck Labs, Servier, and Syndax; as a consultant for AbbVie, Magenta, Molecular Partners, and Takeda; as a member of a speakers bureau for BMS, Incyte, and Servier; and for research funding from Aprea and Jazz. VH has received payment as speaker with honoraria from Novartis, support for attending meetings from Novartis and Abbvie, and as member of data safety monitoring board with Incyte and Novartis. ESW has received consulting fees from Abbvie, AmGen, Astellas, BMS, Gilead, GlaxoSmithKline, Janssen, Jazz, Kite, Mana, Novartis, NuProbe, Pfizer, PharmaEssentia, and Takeda; and payment as member of data safety monitoring board or speaker bureau from Abbvie, Astellas, CTI Biopharma, Dava oncology, Gilead, Novartis, Kite, Pfizer, Rafael, and Stemline. MLD has received licensing fees from Atara and CRISPR; research funds from Atara, CRISPR, Kite, and Novartis; and consulting fees from Synthekine, Adicet, and Bellicum. J-PM has received payment as an advisory board member or speaker with honoraria from Pfizer, Roche, AstraZeneca, Bayer, Innate, Merck Serono, Boerhinger, BMS, Novartis, Janssen, Incyte, Cue Biopharma, ALX Oncology, iTEOS, eTheRNA, NEKTAR, and F-Star; and as member of a data safety monitoring board with honoraria for Psioxus. AA took part in advisory boards from Amgen, AstraZeneca, Bayer, Daiichi, EISAI, Genomic Health, Hengrui, Innate, Ipsen, Leo Pharma, Lilly, Merck, MSD, Novartis, Pfizer, and Seattle Genetics; received speaker fees from Amgen, AstraZeneca, Bayer, Daiichi, EISAI, Genomic Health, Ipsen, Leo Pharma, Lilly, Merck, Merck Sharpe and Dohme, Novartis, Pfizer, and Seattle Genetics; and research grants from BMS, Roche. EMA-O, RB, NB, M-SD, DEG, CL, FFL and AF are or were employed by Celyad Oncology. RB, NB, M-SD, DEG, CL, FFL, and AF are or were employed by Celyad Oncology. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: Funding No external funding has been received for the preparation of this guideline. Production costs have been covered by ESMO from central funds.

The effects of the COVID-19 pandemic continue to constrain health-care staff and resources worldwide, despite the availability of effective vaccines. Aerosol-generating procedures such as endoscopy, a common investigation tool for nasopharyngeal carcinoma, are recognised as a likely cause of SARS-CoV-2 spread in hospitals. Plasma Epstein-Barr virus (EBV) DNA is considered the most accurate biomarker for the routine management of nasopharyngeal carcinoma. A consensus statement on whether plasma EBV DNA can minimise the need for or replace aerosol-generating procedures, imaging methods, and face-to-face consultations in managing nasopharyngeal carcinoma is urgently needed amid the current pandemic and potentially for future highly contagious airborne diseases or natural disasters. We completed a modified Delphi consensus process of three rounds with 33 international experts in otorhinolaryngology or head and neck surgery, radiation oncology, medical oncology, and clinical oncology with vast experience in managing nasopharyngeal carcinoma, representing 51 international professional societies and national clinical trial groups. These consensus recommendations aim to enhance consistency in clinical practice, reduce ambiguity in delivering care, and offer advice for clinicians worldwide who work in endemic and non-endemic regions of nasopharyngeal carcinoma, in the context of COVID-19 and other airborne pandemics, and in future unexpected settings of severe resource constraints and insufficiency of personal protective equipment., Competing Interests: Declaration of interests VH-FL reports personal fees and grants from AstraZeneca; and personal fees from AQUILAB, Amgen, Boston Scientific, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, and Takeda, all outside this Policy Review. GFH reports fees paid to the institution from Eli Lilly, Regeneron, Merck Sharp and Dohme, AB Science, Astellas, Tessa Therapeutics, Roche, Arcus Bioscience, AstraZeneca, and Pfizer; and personal fees from Merck Sharp and Dohme, Novartis, Roche, AstraZeneca, Boehringer Ingelheim, Pfizer, Ipsen, Bristol Myers Squibb, Janssen, and Taiho, all outside the scope of this Policy Review. WKJL is a shareholder of Illumina/GRAIL. Q-TL reports personal fees from the RTOG Foundation and NRG Oncology, outside the scope of this Policy Review, and is supported by the US National Institutes of Health (2U10CA180868-06, 1R01DE029672-01A1, P30CA124435, and R01DE030894-01A1). NYL is supported by the US National Institutes of Health (R01 CA238392-02A1 and 5UG1CA233290-02). DW-TL reports institutional fees from Bristol Myers Squibb, Merck Sharp and Dohme, Boehringer Ingelheim, Janssen, and Novartis, outside the scope of this Policy Review. RM reports personal fees from Merck Pharmaceuticals, Merck Sharp and Dohme, Bristol Myers Squibb, Roche, Amgen, AstraZeneca, Nanobiotix, Seattle Genetics, and Boehringer Ingelheim, all outside the scope of this Policy Review. RK-CN reports personal fees from Pfizer, Novartis, Sanofi, AstraZeneca, Eli Lilly, Merck Sharp and Dohme, Zai Lab, Roche, Eisai, Merck Pharmaceutical, Astellas, and Nuance (China), outside the scope of this Policy Review. RK-YT is the President of Hong Kong Society of Otolaryngology, Head and Neck Surgery, and past President of Hong Kong Head and Neck Society. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The anti-CD38 antibody isatuximab is approved for the treatment of relapsed/refractory multiple myeloma, but there are no data on its efficacy in solid tumors. This phase I/II study (NCT03637764) assessed the safety and activity of isatuximab plus atezolizumab (Isa + Atezo), an anti-programmed death-ligand 1 (PD-L1) antibody, in patients with immunotherapy-naive solid tumors: epithelial ovarian cancer (EOC), glioblastoma (GBM), hepatocellular carcinoma (HCC), and squamous cell carcinoma of the head and neck (SCCHN)., Patients and Methods: Phase I assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and the recommended phase II dose (RP2D) of isatuximab 10 mg/kg intravenously (i.v.) every week for 3 weeks followed by once every 3 weeks + atezolizumab 1200 mg i.v. every 3 weeks. Phase II used a Simon's two-stage design to assess the overall response rate or progression-free survival rate at 6 months (GBM cohort). Interim analysis was carried out at 6 months following first dose of the last enrolled patient in each cohort. Pharmacodynamic biomarkers were tested for CD38, PD-L1, tumor-infiltrating immune cells, and FOXP3+ regulatory T cells (Tregs) in the tumor microenvironment (TME)., Results: Overall, 107 patients were treated (EOC, n = 18; GBM, n = 33; HCC, n = 27; SCCHN, n = 29). In phase I, Isa + Atezo showed an acceptable safety profile, no dose-limiting toxicities were observed, and RP2D was confirmed. Most patients experienced ≥1 treatment-emergent adverse event (TEAE), with ≤48.5% being grade ≥3. The most frequent TEAE was infusion reactions. The study did not continue to stage 2 based on prespecified targets. Tumor-infiltrating CD38+ immune cells were reduced and almost cleared after treatment. Isa + Atezo did not significantly modulate Tregs or PD-L1 expression in the TME., Conclusions: Isa + Atezo had acceptable safety and tolerability. Clinical pharmacodynamic evaluation revealed efficient target engagement of isatuximab via treatment-mediated reduction of CD38+ immune cells in the TME. Based on clinical data, CD38 inhibition does not improve responsiveness to PD-L1 blockade in these patients., Competing Interests: Disclosure EG: Sanofi, Roche/Genentech, F. Hoffman La Roche, Ellipses Pharma, Neomed Therapeutics, Boehringer Ingelheim, Janssen Global Services, SeaGen, TFS, Alkermes, Thermo Fisher, Bristol Myers Squibb, MabDisovery, Novartis, AstraZeneca, Taiho, BeiGene, Merck Sharp & Dohme, Menarini, Glycotope. SL: Bristol Myers Squibb, Merck Serono, Bayer, Roche, Amgen, Servier, AstraZeneca, Lilly, Incyte, Daiichi-Sankyo, MSD. BM: Sanofi, Roche, BMS, Merck Serono, MSD, Pfizer, Astellas, Novartis, Bayer, Servier, AstraZeneca, Amgen, Janssen, Eisai, Eli Lilly, Pierre Farbre. VM: BMS, Bayer, Janssen, Pieris. MLY: Abbott, BMS, Gilead, Merck, AbbVie, Ascletis, Roche, Ipsen. EC: Nanobiotix, Novartis, BMS, Roche/Genentech, Servier, OncoDNA, Alkermes, PharmaMar, Beigene, PsiOxus Therapeutics, HM Hospitals Group and START Program, INTHEOS. JPM: Roche, AstraZeneca, Bayer, Innate, Merck Serono, Boehringer Ingelheim, BMS, Novartis, Janssen, Incyte, Cue Biopharma, ALX Oncology, Amgen, Pfizer, MSD, Psioxus Debio, Nanobiotix. AGM: GSK/Tesaro, Roche, AstraZeneca, Clovis, Genmab, Immunogen, MSD, Amgen, Oncoinvent, Merck/Pfizer, Pharmamar, SOTIO, GSK/Tesaro. LPA: MSD, BMS, Roche, AstraZeneca, Lilly, Merck, Novartis, Amgen, Incyte, Takeda, Bluprint, Bayer. CCL: BeiGene, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Novartis, Roche. DAR: Acerta Pharmaceuticals, Agenus, Celldex, EMD Serono, Incyte, Inovio, Midatech, Omniox, Tragara, AbbVie, Advantagene, Amgen, Bayer, Bristol Myers Squibb, DelMar, Genentech/Roche, Merck, Monteris, Novocure, Regeneron. AS: Bristol Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer, Merck Sharp & Dohme, Arqule, Sanofi, Takeda, Roche, AbbVie, Amgen, Celgene, AstraZeneca, Lilly, Sandoz, Novartis. RM, GA, FM, HL, QL, CC, NT, and SZL are employed by Sanofi and may hold stock and/or stock options in the company. CM: Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion. All other authors have declared no conflicts of interest. Data sharing Qualified researchers can request access to patient-level data and related study documents including the clinical study report, study protocol with any amendments, blank case report forms, statistical analysis plan, and dataset specifications. Patient-level data will be anonymized, and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi’s data-sharing criteria, eligible studies, and process for requesting access are at: https://www.vivli.org., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The phase II TALAPRO-1 study (NCT03148795) demonstrated durable antitumor activity in men with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). Here, we detail the safety profile of talazoparib., Patients and Methods: Men received talazoparib 1 mg/day (moderate renal impairment 0.75 mg/day) orally until radiographic progression, unacceptable toxicity, investigator decision, consent withdrawal, or death. Adverse events (AEs) were evaluated: incidence, severity, timing, duration, potential overlap of selected AEs, dose modifications/discontinuations due to AEs, and new clinically significant changes in laboratory values and vital signs., Results: In the safety population (N = 127; median age 69.0 years), 95.3% (121/127) experienced all-cause treatment-emergent adverse events (TEAEs). Most common were anemia (48.8% [62/127]), nausea (33.1% [42/127]), decreased appetite (28.3% [36/127]), and asthenia (23.6% [30/127]). Nonhematologic TEAEs were generally grades 1 and 2. No grade 5 TEAEs or deaths were treatment-related. Hematologic TEAEs typically occurred during the first 4-5 months of treatment. The median duration of grade 3-4 anemia, neutropenia, and thrombocytopenia was limited to 7-12 days. No grade 4 events of anemia or neutropenia occurred. Neither BRCA status nor alteration origin significantly impacted the safety profile. The median (range) treatment duration was 6.1 (0.4-24.9) months; treatment duration did not impact the incidence of anemia. Only 3 of the 15 (11.8% [15/127]) permanent treatment discontinuations were due to hematologic TEAEs (thrombocytopenia 1.6% [2/127]; leukopenia 0.8% [1/127])., Conclusion: Common TEAEs associated with talazoparib could be managed through dose modifications/supportive care. Demonstrated efficacy and a manageable safety profile support continued evaluation of talazoparib in mCRPC., Clinicaltrials.gov Identifier: NCT03148795., (© The Author(s) 2022. Published by Oxford University Press.)

Background: This phase 1b study (NCT02323191) evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of colony-stimulating factor-1 receptor-blocking monoclonal antibody (mAb) emactuzumab in combination with the programmed cell death-1 ligand (PD-L1)-blocking mAb atezolizumab in patients with advanced solid tumors naïve or experienced for immune checkpoint blockers (ICBs)., Methods: Emactuzumab (500-1350 mg flat) and atezolizumab (1200 mg flat) were administered intravenously every 3 weeks. Dose escalation of emactuzumab was conducted using the 3+3 design up to the maximum tolerated dose (MTD) or optimal biological dose (OBD). Extension cohorts to evaluate pharmacodynamics and clinical activity were conducted in metastatic ICB-naive urothelial bladder cancer (UBC) and ICB-pretreated melanoma (MEL), non-small cell lung cancer (NSCLC) and UBC patients., Results: Overall, 221 patients were treated. No MTD was reached and the OBD was determined at 1000 mg of emactuzumab in combination with 1200 mg of atezolizumab. Grade ≥3 treatment-related adverse events occurred in 25 (11.3%) patients of which fatigue and rash were the most common (14 patients (6.3%) each). The confirmed objective response rate (ORR) was 9.8% for ICB-naïve UBC, 12.5% for ICB-experienced NSCLC, 8.3% for ICB-experienced UBC and 5.6% for ICB-experienced MEL patients, respectively. Tumor biopsy analyses demonstrated increased activated CD8 +tumor infiltrating T lymphocytes (TILs) associated with clinical benefit in ICB-naïve UBC patients and less tumor-associated macrophage (TAM) reduction in ICB-experienced compared with ICB-naïve patients., Conclusion: Emactuzumab in combination with atezolizumab demonstrated a manageable safety profile with increased fatigue and skin rash over usual atezolizumab monotherapy. A considerable ORR was particularly seen in ICB-experienced NSCLC patients. Increase ofCD8 +TILs under therapy appeared to be associated with persistence of a TAM subpopulation., Competing Interests: Competing interests: CG-R: Invited Speaker: BMS, Eisai, Pierre Fabre, Roche/Genentech; Coordinating PI: BMS; Steering Committee Member: BMS; Local PI: Foundation Medicine; Steering Committee Member: Genentech; Research Grant: Roche/Genentech; AM: Stock ownership Pegascy, Hifibio Therapeutics, Shattuck Labs, Centessa Pharmaceuticals; Honoraria: BMS, AstraZeneca/MedImmune, Oncovir; Consulting and advisory activities: Lytix Biopharma, Eisai, Pierre Fabre, AstraZeneca, Servier, Roche, Redx Pharma, Sotio, Innate Pharma, ImCheck Therapeutics, MSD, OSE Immunotherapeutics, HIFIBIO Therapeutics, MedinCell, Centessa Pharmaceuticals; Speaker’s bureau: BMS; Research funding: BMS, Boehringer Ingelheim, Transgene, MSD; Travel expenses: MSD, AstraZeneca; SC: Honoraria: Amgen, AstraZeneca, BMS, EISAI, Janssen, MSD, Novartis and Roche; Principal Investigator of Clinical Trials for: Amgen, MSD, Sanofi Aventis, Transgene; Advisory Board: Alderaan Biotechnology, Amgen, AstraZeneca, Oncovita, Seagen, Ultrahuman; Travel and congress: AstraZeneca, MSD, Roche; Principal/sub-investigator of clinical trials for: Abbvie, Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, Astra Zeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, BicycleTx Ltd, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co, Clovis Oncology, Cullinan-Apollo, Curevac, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Faron Pharmaceuticals Ltd, Forma Tharapeutics, Gamamabs, Genentech, Glaxosmithkline, H3 Biomedicine, Hoffmann La Roche Ag, Imcheck Therapeutics, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Iteos Belgium SA, Janssen Cilag, Janssen Research Foundation, Kura Oncology, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, Lytix Biopharma As, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Molecular Partners Ag, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncopeptides, Orion Pharma, Ose Pharma, Pfizer, Pharma Mar, Pierre Fabre, Medicament, Roche, Sanofi Aventis, Seattle Genetics, Sotio A.S, Syros Pharmaceuticals, Taiho Pharma, Tesaro, Turning Point Therapeutics, Xencor; Research Grants from: Astrazeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, SanofiNon-financial support (drug supplied) from Astrazeneca, Bayer, BMS, Boringher Ingelheim, GSK, Medimmune, Merck, NH TherAGuiX, Pfizer, Roche; SA: Speakers bureau: Pfizer, Roche, Sanofi and BMSAdvisory board: Sanofi; PC: Honoraria: Novartis, Roche/Genentech, Amgen, Astra Zeneca, Merck Serono; Research Funding: Novartis, Roche/Genentech, Lilly, lueprint Medicines, Bayer, Astra Zeneca, Celgene, Plexxikon, Abbvie, BMS, Merck Serono, Merck Sharp and Dohme, Taiho Pharmaceutical, Toray Industries, Transgene, Loxo, GSK, Innate Pharma, Janssen; Travel expenses: Roche, Amgen, Novartis, BMS, MSD, Netris Pharma, Bayer, Merck Serono; DZ: Reports research support from: Roche, Astra Zeneca, and Plexxikon; Personal/consultancy fees from Synlogic Therapeutics, GSK, Roche, Xencor, Memgen, Immunos, Celldex, Calidi, and Agenus; J-PM: Advisory board member or speaker with honoraria: Pfizer, Roche, Astra/Zeneca, Bayer, Innate, Merck Serono, Boerhinger, BMS, Novartis, Janssen, Incyte, Cue Biopharma, ALX Oncology, iTEOS, eTheRNATravel expenses: Amgen, BMS, Pfizer, MSDData safety monitoring board with honoraria: Debio, Nanobiotix, Psioxus; Uncompensated advisory role: MSD; JLPG; Research grants and support: Roche, BMS, MSD, Seattle Genetics. Speakers bureau and advisory boards: Roche, BMS, Ipsen, MSD, Seattle Genetics. Travel support: Roche, MSD, BMS; FSH: Consulting: BMS, Merck, EMD Serono, Novartis, Sanofi, Psioxus Therapeutics, Pieris Pharmacutical, Corner Therapeutics, Eisai, Idera, Takeda, Genentech/Roche; Advisory Board: Compass Therapeutics, Apricity Scientific, Pionyr, Torque, Rheos, Bicara, Checkpoint Therapeutics, Bioentre, Gossamer, Iovance; ATG: Personal fees from: Boehringer-Ingelheim, BMS, MSD, Roche, Pfizer, Astra Zeneca, Tesaro-GSK and non-financial support from Boehringer-Ingelheim, Lilly and RocheMaria Martinez Garcia; Research grants and support: Roche, BMS, MSD, Seattle Genetics; Speakers bureau and advisory boards: Roche, BMS, Ipsen, MSD, Seattle Genetics; Travel support: Roche, MSD, BMS; VB: Consulting or Advisory Role: Puma Biotechnology; Ideaya Biosciences; Loxo Therapeutics, CytomX Therapeutics; Guidepoint; Oncoart; Amunix; Institutional financial support for clinical trials from: Abbvie, ACEO, Adaptaimmune, Amcure, AMGEN, AstraZeneca, BMS, Cytomx, GSK, Genentech/Roche, H3, Incyte, Janssen, Kura, Lilly, Loxo, Nektar, Macrogenics, Menarini, Merck, Merus, Nanobiotix, Novartis, Pfizer, PharmaMar, Principia, PUMA, Sanofi, Taiho, Tesaro, BeiGene, Transgene, Takeda, Incyte, Innovio, MSD, PsiOxus, Seattle Genetics, Mersana, GSK, Daiichi, Nektar, Astellas, ORCA, Boston Therapeutics, Dynavax, DebioPharm, Boehringen Ingelheim, Regeneron, Millenium, Synthon, Spectrum, Rigontec, Zenith; JPE: The author declares no potential conflicts of interest. NH: The author declares no potential conflicts of interest. RS: Consultant/advisory boards: Asana Biosciences, AstraZeneca, Bristol-Myers Squibb, Eisai, Iovance, Merck, Novartis, OncoSec, Pfizer, Replimune; Research funding: Amgen, Merck; DM: Consulting and honoraria: BMS, Pfizer, Merck, Alkermes Inc., EMD Serono, Eli Lilly and Company, Iovance, Eisai Inc., Werewolf Therapeutics, Calithera Biosciences; Research support: BMS, Merck, Genentech, Pfizer, Exelixis, X4 Pharma, Alkermes Inc; MAC: Sponsor employee and sponsor stock ownership; A-MJ: Former sponsor employee and has patent issued in the use of emactuzumab; WJ: Sponsor employee and sponsor stock ownership; CR: Former Roche employee and has patent issued in the use of emactuzumab. Consultant for Verseau Therapeutics, Ridgeline Discovery, iOmx Therapeutics AG; KK: Sponsor employee and Roche stocks; GB: Sponsor employee; FM: Sponsor employee; RC: Sponsor employee and Roche stocks; CW: Sponsor consultantGeorgina Meneses-LorenteSponsor employee; MW: Sponsor employee, stock options, and has patent issued in the use of emactuzumab; DR: Sponsor employee, sponsor stock ownership and has patent issued in the use of emactuzumab; J-PD: Consulting/Advisory: Novartis, Roche/Genentech, BMS, MSD; Research funding: Genentech, BMS, MSD, Astra Zeneca, Transgene; CT: Research funding GSK, travel expenses Mundipharma., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Oral potentially malignant disorders (OPMD) may precede oral squamous cell carcinoma (OSCC). Reported rates of malignant transformation of OPMD range from 3 to 50%. While some clinical, histological, and molecular factors have been associated with a high-risk OPMD, they are, to date, insufficiently accurate for treatment decision-making. Moreover, this range highlights differences in the clinical definition of OPMD, variation in follow-up periods, and molecular and biological heterogeneity of OPMD. Finally, while treatment of OPMD may improve outcome, standard therapy has been shown to be ineffective to prevent OSCC development in patients with OPMD. In this perspective paper, several experts discuss the main challenges in oral cancer prevention, in particular the need to (i) to define an OPMD classification system by integrating new pathological and molecular characteristics, aiming (ii) to better identify OPMD at high risk of malignant transformation, and (iii) to develop treatment strategies to eradicate OPMD or prevent malignant transformation.

Whole-Body Magnetic Resonance Imaging (WB-MRI) is increasingly used for metastatic screening in oncology. This prospective single center study assesses the diagnostic value of WB-MRI including diffusion weighted imaging (DWI) and identifies the sufficient protocol for metastatic lymph node detection in patients with testicular germ cell cancer (TGCC). Forty-three patients underwent contrast enhanced thoraco-abdominopelvic CT (TAP-CT) and WB-MRI with DWI for metastatic lymph node screening. Two independent readers reviewed CTs and WB-MRIs. The diagnostic performance of different imaging protocols (CT, complete WB-MRI, T1W + DWI, T2W + DWI), the agreement between these protocols and the reference standard, the reproducibility of findings and the image quality (Signal and contrast to Noise Ratios, Likert scale) were studied. Reproducibility was very good regardless of both lesion locations (retroperitoneal vs distant lymph nodes, other lesions) and the reader. Diagnostic accuracy of MRI was ≥95% (regardless of the locations and imaging protocol); accuracy of CT was ≥93%. There was a strict overlap of 95% CIs associated with this accuracy between complete WB-MRI, T1W + DWI and T2W + DWI, regardless of the reader. Higher Likert score and SNR were observed for DWI, followed by T2W and T1W sequences. In conclusion, a fast WB-MRI protocol including T2W and DWI is a sufficient, accurate, non-irradiating alternative to TAP-CT for metastatic lymph node screening in TGCC.

Multiple factors differentially influence treatment decisions in the first line treatment of recurrent/metastatic HNSCC. The EORTC Young investigator group launched a survey among treating physicians to explore the main influencing factors for treatment stratification. The questionnaire was posted as a web-survey link from May to August 2020. Next to defining the factors that mostly influence therapeutic decision the survey was complemented by a clinical case discussion of five patient cases. A total of 118 responses from 19 countries were collected. The key factors identified to guide treatment decision were performance status, PD-L1 Expression, time from last systemic treatment above or below 6 months, and disease burden. Prospective evaluation of patient characteristics and additional potential predictive biomarkers for novel treatment options remains an important question to stratify personalized treatment for RM HNSCC., Competing Interests: KK: Advisory board participation, invited speaker or conference honoraria from: Merck, Sanofi, Merck Sharp & Dohme, Bristol-Myers Squibb. CS: grants from Roche, grants from Intuitive, personal fees from Pfizer, personal fees from Merck, personal fees from MSD, personal fees from Seattle Genetics, outside the submitted work. J-PM: Advisory board member or speaker with honoraria (managed by my Institution): Pfizer, Roche, Astra/Zeneca, Bayer, Innate, Merck Serono, Boerhinger, BMS, Novartis, Janssen, Incyte, Cue Biopharma, ALX Oncology, iTEOS, eTheRNA. Travel expenses: Amgen, BMS, Pfizer, MSD. Data safety monitoring board with honoraria: Debio, Nanobiotix, Psioxus; Uncompensated advisory role: MSD; EORTC: investigator and study coordinator, H & N group Chair. PB: Advisory board participation or conference honoraria from: Merck, Sanofi, Merck Sharp & Dohme, Sun Pharma, Angelini, Molteni, Bristol-Myers Squibb, GSK. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Klinghammer, Lorini, Nevens, Simon, Machiels and Bossi.)

Squamous cell carcinoma of the head and neck (SCCHN) is among the most prevalent cancer types worldwide. Despite multimodal therapeutic approaches that include surgical resection, radiation therapy or concurrent chemoradiation, targeted therapy and immunotherapy, SCCHN is still associated with a poor prognosis for patients with locally advanced or recurrent/metastatic (R/M) diseases. Although next-generation sequencing data from thousands of SCCHN patients have provided a comprehensive landscape of the somatic genomic alterations in this disease, genomic-based precision medicine is not implemented yet in routine clinical use since no satisfactory genetic biomarker has been identified for diagnosis, patient outcome prediction and selection of tailored therapeutic options. The lack of significant improvement in SCCHN patient survival over the last decades stresses the need for reliable predictive biomarkers and new therapeutic strategies for personalized clinical management of SCCHN patients. Targeting the SCCHN-associated microenvironment or the interaction of the latter with cancer cells may represent such paradigm shift in the development of new strategies to treat SCCHN patients, as exemplified by the recent implementation of immune checkpoint inhibitors to improve clinical outcomes by increasing anti-tumor immune responses in SCCHN patients. Several clinical trials are in progress in SCCHN patients to evaluate the activity of monoclonal antibodies and small-molecule inhibitors targeting the tumor microenvironment (TME) at different treatment settings, including combinations with adjuvant surgery, radiation therapy and chemotherapy. This review describes the current knowledge about the influence of the TME on intratumoral heterogeneity and clinical relapse in human SCCHN patients. More precisely, the role of hypoxia as well as the presence of non-cancer cells (e.g. cancer-associated fibroblasts and immune cells) on therapy response of SCCHN cells is highlighted. We also discuss relevant (pre)clinical models that may help integrate the microenvironment-tumor cell interplay in translational research studies for SCCHN. Finally, this review explores potential therapeutic strategies that may exploit the crosstalk between TME and SCCHN cells in order to implement fundamental changes in the tumor treatment paradigm of patients with locally advanced or R/M SCCHN., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To assess the safety and tolerability of BMS-986148, a mesothelin-directed antibody-drug conjugate (ADC) ± nivolumab, in patients with selected tumors., Patients and Methods: In an international phase I/IIa study [NCT02341625 (CA008-002)], patients received BMS-986148 monotherapy (0.1-1.6 mg/kg intravenously (i.v.) every 3 weeks or 0.4 or 0.6 mg/kg i.v. once weekly; n = 96) or BMS-986148 0.8 mg/kg + nivolumab 360 mg i.v. every 3 weeks ( n = 30). The primary endpoint was safety and tolerability., Results: In CA008-002, the most common (≥ 10%) treatment-related adverse events (TRAEs) included increased aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Grade 3/4 TRAEs occurred in 42 patients (49%) receiving BMS-986148 every 3 weeks monotherapy, three (25%) receiving BMS-986148 once-weekly monotherapy, and 10 (33%) receiving BMS-986148 + nivolumab every 3 weeks. Overall, 17 of 126 patients (13%) discontinued because of a TRAE. The MTD of BMS-986148 was 1.2 mg/kg i.v. every 3 weeks. The safety profile of BMS-986148 + nivolumab was similar to that of BMS-986148 monotherapy (0.8 mg/kg). Active ADC exposures increased in a dose-proportional manner with both dosing regimens (every 3 weeks and once weekly). Preliminary clinical activity was observed with BMS-986148 ± nivolumab. No association between mesothelin expression and response was detected., Conclusions: BMS-986148 ± nivolumab demonstrated a clinically manageable safety profile and preliminary evidence of clinical activity, supporting additional studies combining directed cytotoxic therapies with checkpoint inhibitors as potential multimodal therapeutic strategies in patients with advanced solid tumors., (©2021 The Authors; Published by the American Association for Cancer Research.)

Fusions of NTRK (neurotrophic tyrosine receptor kinase) genes with 5' partner genes can result in the expression of chimeric proteins that drive oncogenesis through ligand-independent kinase activation. Despite variable frequencies of NTRK fusions in different tumor types, the fact that they are common to a wide range of cancers raises the possibility of developing tumor-agnostic treatments specifically targeting NTRK fusion products, irrespective of tumor type. The first-generation Trk (tropomyosin receptor kinase) inhibitor, larotrectinib, was the first tumor-agnostic treatment of NTRK fusion-positive cancers in adults and children, to be approved in the European Union. This consensus, developed by a Belgian multidisciplinary expert panel, aims to highlight the unmet medical need associated to NTRK fusion-driven cancer treatment and, based on current knowledge of NTRK fusions and larotrectinib treatment outcome and safety, provide comprehensive guidance to oncologists regarding NTRK fusion-driven cancer diagnostics and the best use of larotrectinib in real-world clinical settings., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Immune checkpoint inhibitors show high response rates and durable clinical benefit in microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) tumors. However, 50%-60% do not respond to single-agent anti-programmed death-1/programmed death ligand 1 (PD-1/PD-L1) antibodies, and approximately 50% of responders relapse within 6-12 months. This phase Ib trial evaluated safety and antitumor activity of anti-PD-L1 antibody LY3300054 monotherapy or in combination with anti-TIM-3 antibody LY3321367 in patients with MSI-H/dMMR advanced solid tumors., Patients and Methods: Eligible patients ≥18 years without prior anti-PD-1/PD-L1 therapy received LY3300054 monotherapy ( N = 40) or combination ( N = 20); patients with PD-1/PD-L1 inhibitor-resistant/refractory tumors received the combination ( N = 22). LY3300054 (700 mg) and anti-TIM-3 antibody (cycles 1-2: 1,200 mg, cycle 3 onward: 600 mg) were administered intravenously every 2 weeks. Primary endpoints were safety and tolerability., Results: Eighty-two patients were enrolled. Most had colorectal ( n = 39, 47.6%) or endometrial ( n = 14, 17.1%) tumors. More than 70% of patients in the PD-1/PD-L1 inhibitor-resistant/refractory combination cohort had received ≥3 treatment lines. Treatment-related adverse events (TRAE) occurred in 22 patients (55.0%) receiving monotherapy, 13 (65.0%) in the PD-1/PD-L1 inhibitor-naïve combination cohort, and 6 (27.3%) in the PD-1/PD-L1 inhibitor-resistant/refractory combination cohort. A total of 2 patients (5.0%) receiving monotherapy and 3 (7.1%) receiving the combination experienced grade ≥3 TRAEs. Objective responses occurred in 13 patients (32.5%) with monotherapy, 9 (45.0%) in the PD-1/PD-L1 inhibitor-naïve combination cohort, and 1 patient (4.5%) in the PD-1/PD-L1 inhibitor-resistant/refractory combination cohort., Conclusions: LY3300054 monotherapy and combined LY3300054/anti-TIM-3 had manageable safety profiles. Both regimens showed promising clinical activity against PD-1/PD-L1 inhibitor-naïve MSI-H/dMMR tumors. The combination had limited clinical benefit in patients with PD-1/PD-L1 inhibitor-resistant/refractory MSI-H/dMMR tumors., (©2021 American Association for Cancer Research.)

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of squamous cell carcinoma (SCC) of the oral cavity, larynx, oropharynx and hypopharynx was published in 2020. It was therefore decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special, virtual guidelines meeting in July 2021 to adapt the ESMO 2020 guidelines to consider the potential ethnic differences associated with the treatment of SCCs of the head and neck (SCCHN) in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with SCCHN (excluding nasopharyngeal carcinomas) representing the oncological societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter was discussed when appropriate. This manuscript provides a series of expert recommendations (Clinical Practice Guidelines) which can be used to provide guidance to health care providers and clinicians for the optimisation of the diagnosis, treatment and management of patients with SCC of the oral cavity, larynx, oropharynx and hypopharynx across Asia., Competing Interests: Disclosure BK declares grants or contracts from Merck Sharp & Dohme (MSD) Oncology, Ono Pharmaceutical and AstraZeneca, consulting fees from AstraZeneca, MSD Oncology, ABL Bio, Genexine, Cellid, Handok, Celid, Trial Informatics and CBS Bio, payment or honoraria from MSD Oncology and Merck. J-PM declares consulting fees/honoraria from Pfizer, Roche, AstraZeneca, Bayer, Innate, Merck Serono, Boehringer, Bristol Myers Squibb (BMS), Novartis, Janssen, Incyte, Cue Biopharma, ALX Oncology, iTEOS, TheRNA and NEKTAR, support for attending meetings and/or travel from Amgen, Pfizer and MSD and participation at a Safety or Advisory Board for PsiOxus. LL declares institutional grants or contracts from AstraZeneca, BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis Inc, Debiopharm International SA, Hoffman-La Roche Ltd., IRX Therapeutics Inc., Medpace Inc., Merck-Serono, MSD, Novartis, Pfizer, Roche Spa and Buran and receipt of honoraria or fees (for public speaking/teaching in medical meetings and/or for providing expert opinion in Advisory Boards) for AstraZeneca, Bayer, BMS, Eisai, MSD, Merck-Serono, Boehringer Ingelheim, Hoffman La Roche Ltd., Novartis, Roche, Debiopharm International SA, Sobi, Incyte Biosciences Italy SRL, Doxa Pharma, Amgen, Nanobiotics and GlaxoSmithKline (GSK). CB declares payment or honoraria from Merck KGaA, BMS and Roche. MT declares consulting fees from Ono Pharmaceuticals, MSD, BMS and Merck Biopharma, and honoraria from Eisai, Ono Pharmaceuticals, BMS and Merck Biopharma. MA declares consulting fees from MSD, AstraZeneca, Eli Lilly, DKSH, Eisai, Roche, Novartis and Merck, payment or honoraria from MSD, AstraZeneca, Eli Lilly, DKSH, Eisai, Roche, Novartis and Merck, support for attending meetings and/or travel from MSD, Roche, Elekta/Abex and AstraZeneca, and is the president of the Malaysian Oncological Society. MKA declares honoraria for presentations from Pfizer and Boehringer Ingelheim, sponsorship for meetings from AstraZeneca, Boehringer Ingelheim and DKSH. QSNg declares support for attending meetings and or travel from BMS, Boehringer Ingelheim, MSD and Astellas, and participation in Safety or Advisory Boards for MSD and Boehringer Ingelheim. WIWZ declares honoraria for lectures from Amgen Malaysia, DKSH Malaysia, Eisai Malaysia, Eli Lilly Malaysia, Ipsen Malaysia, MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Merck Serono Malaysia, Pfizer Malaysia and Roche Malaysia, travel grants from Amgen Malaysia, Celgene Malaysia, Eisai Malaysia, Eli Lilly Malaysia, MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Roche Malaysia, participation on an Advisory Board for Celgene Malaysia, Roche Malaysia, Eli Lilly Malaysia, Eisai Malaysia and MSD Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and is a member of ASCO AP Regional Council and Greater Petaling Cancer City Challenge UICC. NK declares institutional grants or contracts from Ono Pharmaceutical, BMS, AstraZeneca, Pfizer, Chugai Pharmaceutical, Rakuten Medical, Bayer and Adlai Nortye, payment or honoraria from Ono Pharmaceutical, BMS, Merck Biopharma, MSD, Eisai and Bayer, participation on a Data Safety Monitoring Board or Advisory Board for Bayer and Adlai Nortye. GC declares institutional grants from Merck, consulting fees from BMS, Pfizer, MSD, AstraZeneca, Daichii Sankyo, Lilly, Novartis and Seattle Genetics, payment or honoraria from AstraZeneca, Roche and Daichii Sankyo. SP declares fees for consultancy/advisory roles from AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, BMS, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, Foundation Medicine, Illumina, Imedex, Incyte, Janssen, Medscape, MSD, Merck Serono, Merrimack, Novartis, PharmaMar, Phosplatin Therapeutics, PER, Pfizer, PRIME, Regeneron, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, speaker roles for AstraZeneca, Boehringer Ingelheim, BMS, ecancer, Eli Lilly, Illumina, Imedex, Medscape, MSD, Novartis, PER, Pfizer, Prime, Roche/Genentech, RTP, Sanofi, Takeda and the receipt of grants/research support: (Sub) investigator in trials (institutional financial support for trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, BMS, Clovis, GSK, Illumina, Lilly, MSD, Merck Serono, Mirati, Novartis, and Pfizer, Phosplatin Therapeutics, Roche/Genentech. TWK declares institutional grants or contracts from Roche, and sanofi-aventis. TY declares institutional grants or contracts from Taiho Pharmaceutical, Sumitomo Dainippon, Ono Pharmaceutical, Chugai Pharmaceutical, Amgen, Parexel International, MSD, Daiichi-Sankyo and Sanofi. All other authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In 2019, the FDA approved pembrolizumab, a monoclonal antibody targeting PD-1, for the first-line treatment of recurrent or metastatic head and neck cancers, despite only a limited number of patients benefiting from the treatment. Promising effects of therapeutic vaccination led the FDA to approve the use of the first therapeutic vaccine in prostate cancer in 2010. Research in the field of therapeutic vaccination, including possible synergistic effects with anti-PD(L)1 treatments, is evolving each year, and many vaccines are in pre-clinical and clinical studies. The aim of this review article is to discuss vaccines as a new therapeutic strategy, particularly in the field of head and neck cancers. Different vaccination technologies are discussed, as well as the results of the first clinical trials in HPV-positive, HPV-negative, and EBV-induced head and neck cancers.