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Ibrahim Azar,1 Samer Alkassis,2 Jami Fukui,3 Fares Alsawah,1 Kalub Fedak,1 Mohammed Najeeb Al Hallak,1 Ammar Sukari,1 Misako Nagasaka1,4 1Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, Detroit, MI, USA; 2Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI, USA; 3University of Hawaii Manoa Cancer Center, John A. Burns School of Medicine, Honolulu, HI, USA; 4Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, JapanCorrespondence: Misako NagasakaDepartment of Oncology, Karmanos Cancer Center/Wayne State University, Detroit, MI, USATel +1313-576-8772Fax +1313-576-8699Email nagasakm@hs.uci.eduAbstract: Human epidermal growth factor receptor 2 (HER2) is a proto-oncogene that, when mutated or overexpressed, plays an important role in oncogenesis. The landscape of HER2-positive breast cancer has changed dramatically over the past 2 decades with the FDA approval of a growing number of agents (antibodies, tyrosine kinase inhibitors, and antibody-drug conjugates) targeting the HER2 receptor. HER2 inhibition has also been approved for HER2-positive gastric cancer. HER2 is amplified in 9% and mutated in 3% of lung cancer. Historically, HER2-targeted therapy for lung cancer with trastuzumab, pertuzumab, and trastuzumab emtansine has failed to demonstrate a survival benefit. Trastuzumab deruxtecan (T-DXd) is a novel antibody–drug conjugate with a tetrapeptide linker, which delivers a topoisomerase I inhibitor with a drug-to-antibody ratio of 7∼ 8. The potency of the active payload, as well as its significant bystander effect, resulted in significant anti-tumor activity. The DESTINY-Lung01 trial evaluated T-DXd in HER2-positive non-squamous non-small cell lung cancer (NSCLC) and reported a progression-free survival of 14 months in HER2-mutated NSCLC, earning its breakthrough designation by the FDA. In this review, we will discuss the structural characteristics, pharmacodynamics, and pharmacokinetics of T-DXd. We will also shed light on the preclinical and ongoing clinical trials of T-DXd along with future directions in the management of HER2 positive lung cancer.Keywords: T-DXd, DS8201, antibody drug conjugate, HER2

Misako Nagasaka,1,2 Nadine Abdallah,3 Marcus Crosby,4 Nithin Thummala,1 Dhaval Patel,1 Antoinette J Wozniak,5 Shirish Gadgeel,6 Judith Abrams,1 Ammar Sukari1 1Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA; 2Department of Advanced Medical Innovations, St. Marianna University Graduate School of Medicine, Kawasaki, Japan; 3Department of Internal Medicine, Wayne State University, Detroit, MI, USA; 4Department of Radiation Oncology, Gundersen Health System, La Crosse, WI, USA; 5Department of Oncology, University of Pittsburgh, Pittsburgh, PA, USA; 6Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USACorrespondence: Ammar SukariDepartment of Oncology, Karmanos Cancer Institute, Wayne State University, 4100 John R, Detroit, MI 48201, USATel +1 313 576 8753Fax +1 313 576 8699Email sukaria@karmanos.orgIntroduction of hypothesis: Little information is available regarding the imaging characteristics that assist in differentiating responders from non-responders. We hypothesized that patients with higher pretreatment tumor volume (PTV) would have lower response rates and shorter overall survival (OS).Methods: Data from patients who received at least one dose of program death-1 (PD-1) inhibitors before August 31, 2016 were captured from our institution’s pharmacy database. The primary objective was to determine the association of PTV with best response, evaluated utilizing RECIST v1.1 criteria. Secondary objectives were estimation of progression-free survival (PFS) and OS. PTV was measured using the Philips Intellispace Multi-Modality Tumor Tracking application.Results: 116 non-small cell lung cancer (NSCLC) patients were evaluated. 66% patients had adenocarcinoma, 28% had squamous cell carcinoma and 5% had poorly differentiated NSCLC. Median PTV was 53.7 cm3 (95% CI: 13.3–107.9). Only one individual had no metastases and the remainder had M1 disease; 38% M1a, 10% M1b, 51% M1c. Most (79%) were previously treated. There were no complete responses; among those followed for at least 6 weeks, 26% had a partial response, 39% stable disease and 34% PD; 4% had no recorded response. There were no strong associations of PTV with any of the demographic or clinical characteristics. There was no association between PTV and OS (HR 1.2, P=0.26) or PFS (HR 1.1, P=0.47). Liver metastasis was associated with shorter survival (HR=2.8, P=0.05).Conclusion: PTV in NSCLC did not prove to be a predictor of response to PD-1 inhibitors but having liver metastasis was associated with significantly shorter survival.Keywords: non-small cell lung cancer, tumor volume, tumor burden, checkpoint inhibitors

PURPOSE: Nuclear protein in testis carcinoma (NC) is an underdiagnosed and aggressive squamous/poorly differentiated cancer characterized by rearrangement of the gene NUTM1 on chromosome 15q14. Co-occurring alternations have not been fully characterized. METHODS: We analyzed the genomic and immune landscape of 54 cases of NC that underwent DNA- and RNA-based NGS sequencing (Caris). RESULTS: While NC is driven by NUTM1 fusion oncoproteins, co-occurring DNA mutations in epigenetic or cell cycle pathways were observed in 26% of cases. There was no significant difference between the fusion partner of NUTM1 and co-occurring gene mutations. RNA sequencing analysis showed increased MYC pathway activity in NC compared with head and neck squamous cell carcinoma (HNSCC) and lung squamous cell carcinoma (LUSC), which is consistent with the known pathophysiology of NC. Characterization of the NC tumor microenvironment using RNA sequencing revealed significantly lower immune cell infiltration compared with HNSCC and LUSC. NC was 10× higher in patients with HNSCC and LUSC younger than 50 years than in those older than 70 years. CONCLUSION: To our knowledge, this is the first series of NC profiled broadly at the DNA and RNA level. We observed fewer intratumoral immune cells by RNA sequencing, which may be associated with anecdotal data of lack of immunotherapy benefit in NC. High MYC pathway activity in NC supports ongoing trials targeting MYC suppression. The incidence of NC among patients younger than 50 years with LUSC/HNSCC supports testing for NC in these patients. The prognosis of NCs remains dismal, and future studies should focus on improving the response to immunotherapy and targeting MYC.

Nadine Abdallah,1 Misako Nagasaka,2,3 Eman Abdulfatah,4 Dongping Shi,4 Antoinette J Wozniak,2 Ammar Sukari2 1Department of Internal Medicine, Wayne State University, Detroit, MI 48201, USA; 2Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; 3Department of Advanced Medical Innovation, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, Japan; 4Department of Pathology, School of Medicine, Wayne State University, Detroit, MI 48201, USA Introduction: Histologic transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a well-recognized mechanism of resistance in EGFR-mutant adenocarcinoma upon treatment with TKIs, but rarely reported with programmed death1 (PD-1) inhibitors. We report two cases of potential transformation during treatment with PD-1 inhibitors.Case presentations: Case 1, a 65-year-old man was diagnosed with stage IVa lung adenocarcinoma on pleural fluid cytology. He received six cycles of carboplatin and pemetrexed, then maintained on pemetrexed. He had disease progression after nine cycles of pemetrexed and was switched to nivolumab. He progressed after five cycles of nivolumab. Core biopsy of the lung mass revealed SCLC. Case 2, a 68-year-old man was diagnosed with two primary NSCLCs and underwent resection. He had recurrence after several months and was treated with four cycles of carboplatin, paclitaxel, and pembrolizumab on clinical trial, with partial response. He was continued on pembrolizumab and had disease progression after 30 cycles. Biopsy of the new lesions showed SCLC.Discussion: Histologic transformation from NSCLC to SCLC can be explained by the presence of a common cell precursor. Proposed molecular mechanisms include loss of RB1, TP53 mutations, and MYC amplification. The distinction between transformation and mixed histology tumors is challenging, especially when pathologic material used for the initial diagnosis is limited. The possibility of a second metachronous primary lung cancer cannot be excluded in our cases.Conclusion: Histologic transformation with PD-1 inhibitors could be under-recognized. Disease progression should prompt re-biopsy to uncover new histology and change in treatment. Future studies are needed to elucidate mechanisms and predictors of transformation. Keywords: transformation, small cell lung cancer, non-small cell lung cancer, PD-1 inhibitor, resistance, checkpoint inhibitor

BACKGROUND: We performed an integrated biomarker evaluation in pembrolizumab-treated patients with R/M HNSCC enrolled in KEYNOTE-012 or KEYNOTE-055. The relationship between biomarkers and HPV status was explored. METHODS: We evaluated PD-L1 (combined positive score [CPS]), TMB, T-cell-inflamed gene expression profile (Tcellinf GEP), and HPV status. Associations between biomarkers were evaluated by logistic regression (ORR) and Cox regression (PFS, OS). RESULTS: Two hundred and fifty-seven patients (KEYNOTE-012, n = 106; KEYNOTE-055, n = 151) had TMB data available; of these, 254 had PD-L1 and 236 had Tcellinf GEP. TMB, PD-L1, and Tcellinf GEP were each significantly associated with ORR (p

PurposeTumoral programmed cell death ligand-1 (PD-L1) expression is common in human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). We assessed whether a DNA vaccine targeting HPV-16/18 E6/E7 with IL12 adjuvant (MEDI0457) combined with the PD-L1 inhibitor durvalumab could enhance HPV-specific T-cell response and improve outcomes in recurrent/metastatic HPV-16/18-associated HNSCC.Patients and methodsIn this phase Ib/IIa study, immunotherapy-naïve patients with ≥1 previous platinum-containing regimen (neoadjuvant/adjuvant therapy or for recurrent/metastatic disease) received MEDI0457 7 mg intramuscularly with electroporation on weeks 1, 3, 7, and 12, then every 8 weeks, plus durvalumab 1,500 mg intravenously on weeks 4, 8, and 12, then every 4 weeks, until confirmed progression and/or unacceptable toxicity. Coprimary objectives were safety and objective response rate (ORR; H0: ORR ≤ 15%); secondary objectives included 16-week disease control rate (DCR-16), overall survival (OS), and progression-free survival (PFS).ResultsOf 35 treated patients, 29 were response evaluable (confirmed HPV-associated disease; received both agents). ORR was 27.6% [95% confidence interval (CI), 12.7-47.2; four complete responses, four partial responses]; responses were independent of PD-L1 tumor-cell expression (≥25% vs. 2-fold increase in tumor-infiltrating CD8+ T cells.ConclusionsMEDI0457 plus durvalumab was well tolerated. While the primary efficacy endpoint was not reached, clinical benefit was encouraging.

Abstract Accurately determining the solubility of ethane in oil‐based mud is crucial for assessing the severity of gas kicks and implementing appropriate well control procedures. The key factors influencing the solubility of ethane gas in oil‐based drilling fluids include the content of base oil, pressure, temperature, and the viscosity of the drilling fluid. This study aims to test the solubility of high‐purity ethane in oil‐based mud under simulated downhole conditions in a 5000 m deep well. The test covers a temperature range of 40–140°C and a partial pressure range of 0.17–5.92 MPa. The effects of temperature, pressure, base oil content, and drilling fluid viscosity on the solubility of ethane are analyzed using various experimental data processing methods. The results show that the variation in ethane solubility with pressure and temperature is nearly linear within the specified ranges. Furthermore, the impact of pressure (1.24–2.78%/MPa) on solubility is approximately 50 times greater than that of temperature (−0.013 to −0.049%/°C) in oil‐based drilling mud. Additionally, ethane's solubility decreases as the drilling fluid's viscosity increases. The ethane solubility in 80% and 90% oil‐based muds is roughly 1.6 times and 2.0 times higher than in 70% oil‐based mud under the same testing conditions. Models for predicting ethane solubility have been developed using screening procedures and statistical regression. These models can be incorporated into gas–liquid flow models to analyze flow behavior during gas kicks.

BACKGROUND: Initial primary head and neck cancer (IPHNC) is associated with second primary lung cancer (SPLC). We studied this association in a population with a high proportion of African American (AA) patients. METHODS: Patients with IPHNC and SPLC treated between 2000 and 2017 were reviewed for demographic, disease, and treatment-related characteristics and compared to age-and-stage-matched controls without SPLC. Logistic and Cox regression models were used to analyze the relationship of these characteristics with the development of SPLC and overall survival (OS). RESULTS: Eighty-seven patients and controls were compared respectively. AA race was associated with a significantly higher risk of developing SPLC (OR 2.92, 95% CI 1.35-6.66). After correcting for immortal time bias, patients with SPLC had a significantly lower OS when compared with controls (HR 0.248, 95% CI 0.170-0.362). CONCLUSIONS: We show that AA race is associated with an increased risk of SPLC after IPHNC; reasons of this increased risk warrant further investigation.

PurposeLocoregional relapse in patients with head and neck squamous cell carcinoma (HNSCC) is common, approaching 50% for some subsites despite multimodality therapy. Salvage surgery is the standard of care, but able to achieve durable control in only a minority of patients. While adjuvant radiotherapy or chemo-radiotherapy is offered to select patients, this approach can be prohibitively toxic. Given the activity and tolerability of programmed death-1 inhibitors in metastatic HNSCC, we investigated the safety and efficacy of adjuvant nivolumab after salvage surgical resection.Patients and methodsThis was an open-label, multi-institutional phase II clinical trial (NCT03355560). Patients with recurrent, resectable HNSCC were enrolled within 6 weeks of salvage surgery. Six 28-day cycles of adjuvant nivolumab were planned. The primary endpoint was 2-year disease-free survival (DFS) more than 58%, based on an institutional historical control group of 71 patients with recurrent HNSCC who underwent salvage surgery.ResultsBetween February 2018 and February 2020, 39 patients were enrolled. At a median follow-up of 22.1 months, 2-year DFS was 71.4% [95% confidence interval (CI), 57.8-88.1] and the 2-year overall survival (OS) was 73% (95% CI, 58-91.8). Three of 39 (8%) patients experienced grade 3 treatment-related adverse events and 3 of 39 (8%) discontinued treatment due to side effects. Ten of 39 had locoregional recurrence, while 2 of 10 also had synchronous metastatic disease. There was no difference in DFS between PD ligand-1 (PD-L1)-positive and PD-L1-negative patients. There was a nonsignificant trend toward improved DFS in patients with high tumor mutational burden (P = 0.083).ConclusionsAdjuvant nivolumab after salvage surgery in locally recurrent HNSCC is well tolerated and showed improved DFS compared with historical controls.

The Indonesian governmentâs decision to relocate the capital to East Kalimantan carries implications for the indigenous Paser people, raising concerns about the potential diminishment of their rich cultural heritage, including the Nondoi ritual. This qualitative research focuses on understanding the construction of the Paser community identity, explicitly emphasizing the Nondoi ritual deeply rooted in ancestral traditions. This study used an ethnographic method to unveil key characteristics within Paserese society through observations and interviews with traditional leaders, community figures, and mulung (shaman). The findings demonstrate that the Nondoi ritual, enriched with religious, spiritual, noble, social, and morally moderate values, plays a pivotal role in expressing and preserving the identity of the Paser community. As East Kalimantan becomes the new capital, the Nondoi ritual is a vital cultural force strenghtening the Paserese identity amidst evolving socio-cultural landscapes.

BACKGROUND: Nuclear protein transport is essential in guiding the traffic of important proteins and RNAs between the nucleus and cytoplasm. Export of proteins from the nucleus is mostly regulated by Exportin 1 (XPO1). In cancer, XPO1 is almost universally hyperactive and can promote the export of important tumor suppressors to the cytoplasm. Currently, there are no studies evaluating XPO1 amplifications and mutations in NSCLC and the impact on outcomes. METHODS: Tumor samples were analyzed using next-generation sequencing (NGS) (NextSeq, 592 Genes), immunohistochemistry (IHC), and whole transcriptome sequencing (WTS, NovaSeq) (Caris Life Sciences, Phoenix, AZ). Survival was extracted from insurance claims data and calculated from time of tissue collection to last contact using Kaplan-Meier estimate. RESULTS: Among 18,218 NSCLC tumors sequenced, 26 harbored XPO1 mutations and 24 had amplifications. XPO1 mutant tumors were more likely to have high TMB (79% vs. 52%, p = 0.007) and less likely to have high PD-L1 (32% vs. 68%, p = 0.03). KRAS co-mutations were seen in 19% (n = 5) and EGFR co-mutations were rare (n = 2). Among the 17,449 NSCLC tumors with clinical data, there were 24 XPO1 mutant. Comparison of survival between XPO1 mutant and WT showed a negative association with a hazard ratio (HR) of 1.932 (95% CI: 1.144-3.264 p = 0.012). XPO1 amplification was not associated with survival. CONCLUSIONS: XPO1 pathogenic mutations were associated with a poor survival in NSCLC. Although XPO1 mutations are rare in NSCLC, further studies to assess its associations with treatment responses are warranted.

Abstract Background Phaleria macrocarpa (Scheff.) Boerl (Thymelaceae) originates from Papua Island, Indonesia and grows in tropical areas. The different parts of the fruit of P. macrocarpa were evaluated for antioxidant, anti-inflammatory, and cytotoxic activities. Methods Phaleria macrocarpa fruit were divided into pericarp, mesocarp and seed. All parts of the fruit were reflux extracted with methanol. The antioxidant activity of the extracts were characterized in various in vitro model systems such as FTC, TBA, DPPH radical, reducing power and NO radical. Anti-inflammatory assays were done by using NO production by macrophage RAW 264.7 cell lines induced by LPS/IFN-γ and cytotoxic activities were determined by using several cancer cell lines and one normal cell line Results The results showed that different parts (pericarp, mesocarp, and seed) of Phaleria macrocarpa fruit contain various amount of total phenolic (59.2 ± 0.04, 60.5 ± 0.17, 47.7 ± 1.04 mg gallic acid equivalent/g DW) and flavonoid compounds (161.3 ± 1.58, 131.7 ± 1.66, 35.9 ± 2.47 mg rutin equivalent/g DW). Pericarp and mesocarp showed high antioxidant activities by using DPPH (71.97%, 62.41%), ferric reducing antioxidant power (92.35%, 78.78%) and NO scavenging activity (65.68%, 53.45%). Ferric thiocyanate and thiobarbituric acid tests showed appreciable antioxidant activity in the percentage hydroperoxides inhibitory activity from pericarp and mesocarp in the last day of the assay. Similarly, the pericarp and mesocarp inhibited inducible nitric oxide synthesis with values of 63.4 ± 1.4% and 69.5 ± 1.4% in macrophage RAW 264.7 cell lines induced by LPS/IFN-γ indicating their notable anti-inflammatory potential. Cytotoxic activities against HT-29, MCF-7, HeLa and Chang cell lines were observed in all parts. Conclusions These results indicated the possible application of P. macrocarpa fruit as a source of bioactive compounds, potent as an antioxidant, anti inflammatory and cytotoxic agents.

Liquid biopsy is now considered a valuable diagnostic tool for advanced metastatic non-small cell lung cancer (NSCLC). In NSCLC, circulating tumor DNA (ctDNA) analysis has been shown to increase the chances of identifying the presence of targetable mutations and has been adopted by many clinicians owing to its low risk. Serial monitoring of ctDNA may also help assess the treatment response or for monitoring relapse. As the presence of detectable plasma ctDNA post-surgery likely indicates residual tumor burden, studies have been performed to quantify plasma ctDNA to assess minimal residual disease (MRD) in early-stage resected NSCLC. Most data on utilizing liquid biopsy for monitoring MRD in early-stage NSCLC are from small-scale studies using ctDNA. Here, we review the recent research on liquid biopsy in NSCLC, not limited to ctDNA, and focus on novel methods such as micro RNAs (miRNA) and long non-coding (lncRNA).

Human epidermal growth factor receptor 2 (HER2) is a proto-oncogene that, when mutated or overexpressed, plays an important role in oncogenesis. The landscape of HER2-positive breast cancer has changed dramatically over the past 2 decades with the FDA approval of a growing number of agents (antibodies, tyrosine kinase inhibitors, and antibody-drug conjugates) targeting the HER2 receptor. HER2 inhibition has also been approved for HER2-positive gastric cancer. HER2 is amplified in 9% and mutated in 3% of lung cancer. Historically, HER2-targeted therapy for lung cancer with trastuzumab, pertuzumab, and trastuzumab emtansine has failed to demonstrate a survival benefit. Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate with a tetrapeptide linker, which delivers a topoisomerase I inhibitor with a drug-to-antibody ratio of 7~8. The potency of the active payload, as well as its significant bystander effect, resulted in significant anti-tumor activity. The DESTINY-Lung01 trial evaluated T-DXd in HER2-positive non-squamous non-small cell lung cancer (NSCLC) and reported a progression-free survival of 14 months in HER2-mutated NSCLC, earning its breakthrough designation by the FDA. In this review, we will discuss the structural characteristics, pharmacodynamics, and pharmacokinetics of T-DXd. We will also shed light on the preclinical and ongoing clinical trials of T-DXd along with future directions in the management of HER2 positive lung cancer.

Mutations in Kirsten rat sarcoma viral oncogene homolog (KRAS) are among the most common aberrations in cancer, including non-small cell lung cancer (NSCLC). The lack of an ideal small molecule binding pocket in the KRAS protein and its high affinity towards the abundance of cellular guanosine triphosphate (GTP) renders the design of specific small molecule drugs challenging. Despite efforts, KRAS remains a challenging therapeutic target. Among the different known mutations; the KRASG12C (glycine 12 to cysteine) mutation has been considered potentially druggable. Several novel covalent direct inhibitors targeting KRASG12C with similar covalent binding mechanisms are now in clinical trials. Both AMG 510 from Amgen and MRTX849 from Mirati Therapeutics covalently binds to KRASG12C at the cysteine at residue 12, keeping KRASG12C in its inactive GDP-bound state and inhibiting KRAS-dependent signaling. Both inhibitors are being studied as a single agent or as combination with other targets. In addition, two novel KRAS G12C inhibitors JNJ-74699157 and LY3499446 will have entered phase 1 studies by the end of 2019. Given the rapid clinical development of 4 direct covalent KRAS G12C inhibitors within a short period of time, understanding the similarities and differences among these will be important to determine the best treatment option based on tumor specific response (NSCLC versus colorectal carcinoma), potential resistance mechanisms (i.e. anticipated acquired mutation at the cysteine 12 residue) and central nervous system (CNS) activity. Additionally, further investigation evaluating the efficacy and safety of combination therapies with agents such as immune checkpoint inhibitors will be important next steps.

Pengabdian ini bertujuan meningkatkan pemahaman moderasi beragama bagi mahasiswa Institut Islam Mamba’ul ‘Ulum dan aktivis masjid di Kota Surakarta melalui penyelenggaraan workshop. Fokusnya mencakup pemahaman moderasi beragama, dialog antarumat beragama, dan pembangunan toleransi. Hasilnya mencakup peningkatan pemahaman moderasi beragama, terjalinnya dialog antarumat beragama, dan peningkatan toleransi di lingkungan kampus dan masjid. Dampaknya tercermin dalam peningkatan kesadaran dan praktik moderasi beragama peserta, dengan pendirian dialog antarumat beragama dan peningkatan toleransi berkontribusi pada menciptakan lingkungan yang lebih harmonis dan inklusif. Ini membina budaya pemahaman dan penghargaan di antara individu dengan latar belakang keagamaan yang beragam.

INTRODUCTION OF HYPOTHESIS: Little information is available regarding the imaging characteristics that assist in differentiating responders from non-responders. We hypothesized that patients with higher pretreatment tumor volume (PTV) would have lower response rates and shorter overall survival (OS). METHODS: Data from patients who received at least one dose of program death-1 (PD-1) inhibitors before August 31, 2016 were captured from our institutions pharmacy database. The primary objective was to determine the association of PTV with best response, evaluated utilizing RECIST v1.1 criteria. Secondary objectives were estimation of progression-free survival (PFS) and OS. PTV was measured using the Philips Intellispace Multi-Modality Tumor Tracking application. RESULTS: 116 non-small cell lung cancer (NSCLC) patients were evaluated. 66% patients had adenocarcinoma, 28% had squamous cell carcinoma and 5% had poorly differentiated NSCLC. Median PTV was 53.7 cm3 (95% CI: 13.3-107.9). Only one individual had no metastases and the remainder had M1 disease; 38% M1a, 10% M1b, 51% M1c. Most (79%) were previously treated. There were no complete responses; among those followed for at least 6 weeks, 26% had a partial response, 39% stable disease and 34% PD; 4% had no recorded response. There were no strong associations of PTV with any of the demographic or clinical characteristics. There was no association between PTV and OS (HR 1.2, P=0.26) or PFS (HR 1.1, P=0.47). Liver metastasis was associated with shorter survival (HR=2.8, P=0.05). CONCLUSION: PTV in NSCLC did not prove to be a predictor of response to PD-1 inhibitors but having liver metastasis was associated with significantly shorter survival.

While immunotherapy with programmed cell death protein 1 (PD1) checkpoint inhibition has shown promising activity against many tumor types, adverse events are common. Hypophysitis is a rare but serious immune-related event known to occur with anti-PD1 inhibition. It will become more prevalent as the usage of checkpoint inhibitors increases.

Purpose There are no approved treatments for recurrent/metastatic head and neck squamous cell carcinoma refractory to platinum and cetuximab. In the single-arm, phase II KEYNOTE-055 study, we evaluated pembrolizumab, an anti-programmed death 1 receptor antibody, in this platinum- and cetuximab-pretreated population with poor prognosis. Methods Eligibility stipulated disease progression within 6 months of platinum and cetuximab treatment. Patients received pembrolizumab 200 mg every 3 weeks. Imaging was performed every 6 to 9 weeks. Primary end points: overall response rate (Response Evaluation Criteria in Solid Tumors v1.1, central review) and safety. Efficacy was assessed in all dosed patients and in subgroups on the basis of programmed death ligand 1 (PD-L1) expression and human papillomavirus (HPV) status. Results Among 171 patients treated, 75% received two or more prior lines of therapy for metastatic disease, 82% were PD-L1 positive, and 22% were HPV positive. At the time of analysis, 109 patients (64%) experienced a treatment-related adverse event; 26 patients (15%) experienced a grade ≥ 3 event. Seven patients (4%) discontinued treatment, and one died of treatment-related adverse events. Overall response rate was 16% (95% CI, 11% to 23%), with a median duration of response of 8 months (range, 2+ to 12+ months); 75% of responses were ongoing at the time of analysis. Response rates were similar in all HPV and PD-L1 subgroups. Median progression-free survival was 2.1 months, and median overall survival was 8 months. Conclusion Pembrolizumab exhibited clinically meaningful antitumor activity and an acceptable safety profile in recurrent/metastatic head and neck squamous cell carcinoma previously treated with platinum and cetuximab.

Background Immune checkpoint inhibitors have profoundly impacted survival among patients with metastatic non–small cell lung cancer. However, population-based studies evaluating this impact on survival by race and socioeconomic factors are lacking. Methods We used the Surveillance, Epidemiology, and End Results Program–Medicare database to identify patients with metastatic non–small cell lung cancer diagnosed between 2015 and 2019. The primary study outcomes were the receipt of an immune checkpoint inhibitor and overall survival. χ2 tests and logistic regression were used to identify demographic factors associated with receipt of immune checkpoint inhibitors. The Kaplan–Meier method was used to calculate 2-year overall survival rates, and log-rank tests were used to compare survival by race and ethnicity. Results Of 17 134 patients, approximately 39% received an immune checkpoint inhibitor. Those diagnosed with cancer recently (in 2019); who are relatively younger (aged younger than 85 years); non-Hispanic White, non-Hispanic Asian, or Hispanic; living in high socioeconomic status or metropolitan areas; not Medicaid eligible; and with adenocarcinoma histology were more likely to receive immune checkpoint inhibitors. The 2-year overall survival rate from diagnosis was 21% for the overall population. The 2-year overall survival rate from immune checkpoint inhibitor initiation was 30%, among those who received at least 1 cycle and 11% among those who did not receive immune checkpoint inhibitors. The 2-year overall survival rates were higher among non-Hispanic White (22%) and non-Hispanic Asian (23%) patients compared with non-Hispanic Black (15%) and Hispanic (17%) patients. There was no statistically significant racial differences in survival for those who received immune checkpoint inhibitors. Conclusion Immune checkpoint inhibitor utilization rates and the resulting outcomes were inferior for certain vulnerable groups, mandating the need for strategies to improve access to care. [ABSTRACT FROM AUTHOR]