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Background: Recent studies suggest improvements in response to salvage chemotherapy (CT) after immune checkpoint inhibitors (ICIs) in several types of cancer. Our objective was to assess the efficacy of chemotherapy re-challenge after ICI, compared with second-line chemotherapy without previous ICI in patients with locally advanced or metastatic urothelial carcinoma (la/mUC)., Methods: In this multicentre retrospective study, we included all patients with la/mUC initiating second or third-line chemotherapy from January 2015 to June 2020. We compared patients treated with second-line chemotherapy without previous ICI (CT2) and patients treated with third-line chemotherapy after ICI (CT3). The primary end-point was objective response rate (ORR) in CT3 compared with CT2. Secondary end-points included progression-free survival (PFS) and toxicities., Results: Overall, 553 patients were included. ORRs were 31.0% (95% CI, 26.5 to 35.5) and 29.2% (95% CI, 21.9 to 36.6), respectively, in CT2 and CT3, with no statistically significant differences (P = 0.62). In subgroup analyses, no differences in ORR were observed by Bellmunt risk group, type of chemotherapy (platinum or taxanes), duration of response to first-platinum-based chemotherapy (< or ≥ 12 months) or FGFR-status. Median PFS was 4.6 months (95% CI, 3.9 to 5.1) and 4.9 months (95% CI, 4.1 to 5.5) in CT2 and CT3, respectively, and grade 3-4 hematologic toxicity occurred in 35.0% and 22.4% of patients., Conclusion: This large multicentre retrospective study provides clinically relevant real-world data. Chemotherapy re-challenge after ICI in la/mUC achieves ORR and PFS comparable with those obtained in CT2 with an acceptable safety profile. These updated results offer more promising outcomes than historically reported with second-line chemotherapy data., Competing Interests: Conflict of interest statement 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 © 2022 Elsevier Ltd. All rights reserved.)

Background: Prior durvalumab (anti-PD-L1 agent) studies in platinum-refractory metastatic urothelial carcinoma evaluated a dose of 10 mg/kg administered every two weeks. The nonrandomised phase 3b STRONG study (NCT03084471) evaluated the safety and efficacy of fixed-dose durvalumab at a more convenient dosing schedule in a previously treated patient population, more similar to a real-world clinical setting., Patients and Methods: 867 patients with urothelial or nonurothelial urinary tract carcinoma (UTC) who progressed on or after platinum or nonplatinum chemotherapy were treated with durvalumab 1500 mg every four weeks; 87% had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, and 13% had an ECOG PS of 2. The primary end-point was the incidence of adverse events of special interest (AESIs), including immune-mediated AEs (imAEs). Secondary and exploratory end-points included overall survival (OS), objective response rate (ORR) and disease control rate (at six and 12 months) (DCR)., Results: AESIs of any grade were reported in 51% of patients (8% grade ≥ 3). The incidence of imAEs was 11% (2% grade ≥ 3). The median OS was 7.0 months (95% confidence interval [CI]: 6.4-8.2) and ORR was 18% (95% CI: 14.8-20.6), with complete responses in 5% of patients and a DCR at six months of 19% (95% CI: 16.1-22.1)., Conclusion: Fixed-dose durvalumab monotherapy every four weeks has an acceptable safety profile and yields durable clinical activity in previously chemotherapy-treated patients with UTC. Safety and efficacy are consistent with previous durvalumab studies and other anti-PD-1/PD-L1 agents in this setting. CLINICALTRIALS., Gov Identifier: NCT03084471https://clinicaltrials.gov/ct2/show/NCT03084471., Competing Interests: Conflict of interest statement The following 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: Sang Joon Shin and Guilhem Roubaud. The following authors declare the following financial interests/personal relationships that may be considered as potential competing interests: Guru P. Sonpavde: Has received grants or contracts (institution) from AstraZeneca, Janssen, and Sanofi; Consulting fees from Astellas Pharma, AstraZeneca, Bicycle Therapeutics, Bristol-Myers Squibb, Eisai, EMD Serono, Exelixis, Genentech, Janssen, Merck, Pfizer and Seattle Genetics; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Medscape, Onclive, Physicans' Education Resource and Research to Practice; Support for attending meetings and/or travel from Bristol-Myers Squibb; Other financial or non-financial interests from Astellas Pharma, AstraZeneca, Bavarian Nordic, Bristol-Myers Squibb, Debiopharm Group, Elsevier and QED Therapeutics. Cora N. Sternberg: Has received consulting fees from Astellas Pharma, AstraZeneca, Bayer, Genzyme, Immunomedics, Incyte, Medscape, Merck, Merck Sharp & Dohme, Pfizer, Roche and UroToday. Yohann Loriot: Has received grants or contracts (institution) from AstraZeneca, Boehringer Ingelheim, Clovis Oncology, CureVac, Exelixis, Incyte, Janssen Oncology, Medivation, Merck Sharp & Dohme Oncology, Nektar, Oncogenex, Pfizer and Sanofi; Consulting fees from Astellas Pharma, AstraZeneca; Clovis Oncology, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme Oncology, Roche and Seattle Genetics and institution consulting fees from Janssen and Merck Sharp & Dohme Oncology; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer and Sanofi; Support for attending meetings and/or travel Astellas Pharma, AstraZeneca; Janssen Oncology, Merck Sharp & Dohme Oncology, Roche and Seattle Genetics. Jae Lyun Lee: Has received grants or contracts (institution) from AstraZeneca/MedImmune, Bayer Schering Pharma, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis, Pfizer and Roche/Genentech and Seattle Genetics; Consulting fees from Alteogen, Bristol-Myers Squibb, GI Innovation, Merck Sharp & Dohme, Pfizer and Sanofi/Aventis; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme and Pfizer; Stock or stock options from Immunomedics and Myovant Sciences. Aurelien Marabelle: Has received grants or contracts (institution) from Boehringer Ingelheim, Bristol-Myers Squibb, MERUS, MSD and Transgene; Consulting fees from AstraZeneca Bayer, Boehringer Ingelheim, CERENIS THERAPEUTICS, Eisai, Gritstone Oncology, HiFiBiO Therapeutics, ImCheck therapeutics, Innate Pharma, Lytix Biopharma, Merck Serono, Molecular Partners, Merck Sharp & Dohme, OSE Immunotherapeutics, Pierre Fabre, Redx Pharma, Roche, Sanofi, SERVIER, Sotio, Symphogen; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme; Support for attending meetings and/or travel from AstraZeneca and Merck Sharp & Dohme; Patents planned, issued or pending from Stanford University (Monoclonal antibodies against CD81); Stock or stock options from HiFiBiO Therapeutics and PEGASCY and PEGASCY (insitition); Other financial or non-financial interests from PEGASCY; Honoraria received from Elsevier as an editor for the European Journal of Cancer. AudeFléchon: Has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events and/or support for attending meetings and/or travel rom Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Ipsen, Janssen-Cilag, Merck Sharp & Dohme Oncology, Pfizer, Roche/Genentech and Sanofi/Aventis. Damien Pouessel: Has received has received grants or contracts (institution) from AstraZeneca, Bristol-Myers Squibb, Incyte, Janssen Oncology, Merck Sharp & Dohme, Roche and Seattle Genetics; Consulting fees from Astellas Pharma, AstraZeneca, Janssen Oncology, Pfizer and Sanofi; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen Oncology and Merck; Support for attending meetings and/or travel from AstraZeneca, Janssen Oncology and Pfizer. Vittorina Zagonel: Has received has received grants or contracts (institution) from Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Ipsen, Lilly and Roche; Consulting fees from Bristol-Myers Squibb and Merck; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, Roche and Servier; Support for attending meetings and/or travel from Bayer, Roche and Servier. Fabio Calabro: Has received consulting fees from Merck Sharp & Dohme Oncology and Pfizer. Giuseppe L. Banna: Has received consulting fees from AstraZeneca, Boehringer Ingelheim, Janssen-Cilag and Roche; Support for attending meetings and/or travel from AstraZeneca/MedImmune, Bristol-Myers Squibb, Ipsen and Pierre Fabre; Patents planned, issued or pending with ST Microelectronics “Deep Learning Motion Algorithm for Lung Cancer Early Detection in Embedded Systems” and “Image processing method, corresponding system and computer program product”. Francisco E. Vera-Badillo: Has received grants or contracts (institution) from AstraZeneca/MedImmune. Thomas Powles: Has received has received grants or contracts, consulting fees and/or payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Eisai, Exelixis, Incyte, Ipsen, Johnson & Johnson, Merck, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche and Seattle Genetics; Support for attending meetings and/or travel from AstraZeneca, Ipsen, Merck Sharp & Dohme, Pfizer and Roche. Eva Hellmis: Has received support for attending meetings and/or travel from Janssen-Cilag. Paulo A. P. Miranda is a current employee of AstraZeneca with AstraZeneca stock or stock options. Ugochi Emeribe and Sun Min Oh are current employees of AstraZeneca. Ana Rita Lima is currently employed as a Third Party Service Provider to AstraZeneca. Sebastien J. Hotte: Has received grants or contracts (institution) from Astellas Pharma, AstraZeneca, Ayala Pharmaceuticals, Bristol-Myers Squibb, Clovis Oncology, Janssen Oncology, Merck, Pfizer, Roche/Genentech, Seattle Genetics and SignalChem; Consulting fees from Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Ipsen, Janssen, Merck, Pfizer and Roche Canada; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astellas Scientific and Medical Affairs Inc, Bayer, Janssen Oncology and Merck; Support for attending meetings and/or travel from Eisai., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Second-line chemotherapy regimens have demonstrated poor benefit after failure of platinum-based chemotherapy in advanced non-squamous non-small-cell lung cancer (nsNSCLC)., Methods: In this multicentre, open-label phase III trial, patients with advanced nsNSCLC treated with one or two prior lines, including one platinum-based doublet, were centrally randomised to receive 90 mg/m 2 of paclitaxel (D1, D8, D15) plus 10 mg/kg of bevacizumab (D1, D15) every 28 days or docetaxel (75 mg/m 2 ) every 21 days; crossover was allowed after disease progression. Primary end-point was progression-free survival (PFS). ClinicalTrials.gov registration number: NCT01763671., Results: One hundred sixty six patients were randomised (paclitaxel plus bevacizumab: 111, docetaxel: 55). The median PFS was longer in patients receiving paclitaxel plus bevacizumab than in patients receveing docetaxel [5·4 months versus 3·9 months, adjusted hazard ratio (HR) 0·61 (95% confidence interval [CI]: 0·44-0·86); p = 0·005]. Objective response rates (ORRs) were 22·5% (95% CI: 14·8-30·3) and 5·5% (95% CI: 0·0-11·5) (p = 0·006), respectively. Median overall survivals were similar (adjusted HR 1·17; p = 0·50). Crossover occurred in 21 of 55 (38·2%) docetaxel-treated patients. Grade III-IV adverse events (AEs) were reported in 45·9% and 54·5% of patients treated with paclitaxel and bevacizumab or docetaxel, respectively (p = NS), including neutropenia (19·3% versus 45·4%), neuropathy (8·3% versus 0·0%) and hypertension (7·3% versus 0·0%). Three patients died due to treatment-related AEs (1·8% in each group)., Conclusion: Weekly paclitaxel plus bevacizumab as second- or third-line improves PFS and ORR compared with docetaxel in patients with nsNSCLC, with an acceptable safety profile. These results place weekly paclitaxel plus bevacizumab as a valid option in this population., Clinical Trials Registration Number: ClinicalTrials.gov Identifier: NCT01763671., Competing Interests: Conflict of interest statement A.B.C. has reported receiveing honoraria from Roche, AstraZeneca, Bristol-Myers Squibb, BoehringerIngelheim, MSD, Novartis and Pfizer and travel grants from Roche, AstraZeneca, BoehringerIngelheim, Novartis and Pfizer. C.A.V. has reported receiving grants, personal fees and non-financial support from Roche. O.M. has received personal fees from BMS, BoehringerIngelheim, Astra Zeneca, Novartis and Hoffman-Roche. F.B. has received personal fees from Astra Zeneca, BMS, BoehringerIngelheim, Clovis Oncology, Eli Lilly Oncology, Hoffman-Roche, Novartis, Merck, MSD, Pierre Fabre and Pfizer. G.Z. has received grant from Roche and BMS, personal fees from Roche, BMS, Astra Zeneca and MSD and non-financial support from BMS, Astra Zeneca and Pfizer. D.P. has received personal fees from Roche Hoffman, Astellas, Lilly, Janssen, BMS, Merck, Astra Zeneca, Novartis, Sanofi and Pfizer. C.F.D. has received other support from MSD (CPLF 2017), Laidet Medical (ERS 2016) and BoehringerIngelheim (CPLF 2016). E.P. has received personal fees and non-financial support from Astra Zeneca and BMS and personal fees from Pfizer. D.M-.S. has received personal fees from Roche, BMS, MSD and Eli Lilly. B.B. has received institutional grants for clinical and translational research from AstraZeneca, BMS, Boehringer-Ingelheim, Lilly, Pfizer, Roche-Genentech, Sanofi-Aventis, Clovis, GSK, Servier, EOS, Onxeo, OncoMed, Inivata and OSE Pharma. All other authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Patients with advanced radioactive iodine resistant differentiated (MDTC) or medullary (MMTC) thyroid cancer had an unmet need. Early data showed promising efficacy of vascular endothelial growth factor receptor inhibitors. We investigated sunitinib in this setting., Patients and Methods: This phase 2 trial enrolled MDTC, anaplastic (MATC) and MMTC patients in 1st line anti-angiogenic therapy with sunitinib at 50 mg/d, 4/6w. Objective response rate was the primary end-point. Secondary end-points were progression-free survival, overall survival and safety., Results: Seventy-one patients were enrolled from August 2007 to October 2009, 41 MDTC/4 MATC patients and 26 MMTC patients. Patients received a median of 8 and 9 cycles, respectively. In the MDTC/MATC group, 13% of patients and 43% of cycles and in the MMTC group, 23% of the patients and 48.8% of cycles remained at 50 mg/d, respectively. The primary end-point was reached with an objective response rate of 22% (95% CI: 10.6-37.6) in MDTC patients and in 38.5% (95% CI: 22.6-56.4) in MMTC patients. No objective response was seen in MATC patients. Median progression-free survival and overall survival were 13.1 and 26.4 months in MDTC patients, 16.5 and 29.4 months in MMTC patients. The most frequent side effects were asthenia/fatigue (27.8% ≥ grade 3), mucosal (9.9% ≥ grade 3), cutaneous toxicities, hand-foot syndrome (18.3% ≥ grade 3). Of all, 14.1% had a cardiac event. Nine unexpected side effects were reported, out of which, five induced deaths., Conclusion: Sunitinib is active in MDTC and MMTC patients. Side effects were more severe than with previous reports. If using sunitinib, alternative schedule/dosage should be considered., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: There is continuing controversy regarding the optimal regimen for neoadjuvant chemotherapy (NAC) in bladder cancer., Patients and Methods: We performed a retrospective analysis of 241 consecutive bladder cancer patients who received a combination of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) using a standard (52 patients) or an accelerated schedule (189 patients) as NAC before radical cystectomy in 17 centres of the French GEnito-urinary TUmour Group from March 2004-May 2013., Results: The median age was 62 years. As expected, the median number of cycles, the median total dose of cisplatin and the median cisplatin dose intensity were higher in patients treated with the accelerated regimen. Conversely, the median duration of chemotherapy was shorter. Regarding toxicity, grade III/IV neutropenia, grade III thrombocytopenia and grade III anaemia as well were more frequently observed in patients treated with the standard regimen. Among 211 (88%) patients who proceeded to cystectomy, 75 (35%) patients achieved an ypT0 pN0 status (no pathologic residual tumour cells) with no significant difference according to the MVAC schedule. Three-year overall survival rates were 66.5% (95% confidence interval [CI], 56-79) and 72% (95% CI, 59.5-88) in the standard and accelerated cohorts, respectively. In the multivariate analysis, two independent prognostic parameters were retained: the ypT0 stage and the ypN0 stage. Heterogeneity test did not show any interaction with NAC regimens., Conclusion: Similar pathological response and survival rates were observed whatever the chemotherapy regimen used. Haematological toxicity was greater in patients who received standard MVAC., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Toxicity, which is a key parameter in the evaluation of cancer treatments, can be underestimated by clinicians. We investigated differences between patients and physicians in reporting adverse events of androgen deprivation therapy (ADT) with or without docetaxel in a multicentre phase III trial in non-castrate metastatic prostate cancer., Methods: The 385 patients included were invited to complete a 26-symptom questionnaire 3 and 6 months after the start of treatment, among which eighteen symptoms were also assessed by physicians, reported in medical records and graded using the Common Toxicity Criteria of the National Cancer Institute. Positive and negative agreements as well as Kappa concordance coefficients were computed., Findings: Data were available for 220 and 165 patients at 3 and 6 months respectively. Physicians systematically under-reported patients' symptoms. Positive agreement rates (at respectively 3 and 6 months) for the five most commonly reported symptoms were: 61.0% and 64.3% hot flushes, 50.0% and 43.6% fatigue, 29.4% and 31.1% sexual dysfunction, 24.4% and 14.4% weigh gain/loss, 16.7% and 19.3% for joint/muscle pain. For symptoms most frequently reported as disturbing or very disturbing by patients, the clinicians' failure to report them ranged from 50.8% (hot flushes) to 89.5% (joint/muscle pain) at 3 months, and from 48.2% (hot flushes) to 88.4% (joint/muscle pain) at 6 months., Interpretation: Physicians often failed to report treatment-related symptoms, even the most common and disturbing ones. Patients' self-evaluation of toxicity should be used in clinical trials to improve the process of drug assessment in oncology., Funding: French Health Ministry and Institut National du Cancer (PHRC), Sanofi-Aventis, Astra-Zeneca, and Amgen., (Copyright © 2013 Elsevier Ltd. All rights reserved.)