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Background: Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC (nccRCC). Pivotal studies evaluating immune checkpoint inhibitors mostly excluded nccRCC. The aim of this retrospective and multicentre study was to evaluate the activity of programmed death-1 (PD-1)/ programmed death-ligand 1 (PD-L1) inhibitors specifically in metastatic pRCC., Methods: The primary end-point was time to treatment failure (TTF). Secondary endpoints included objective response rate (ORR), overall survival (OS) and treatment-related adverse events (TRAEs)., Results: From 02/2016 to 01/2019, 57 patients with pRCC were included. Histology included 16 (28%) type 1 pRCC, 34 (60%) type 2 pRCC and 7 (12%) unclassified pRCC. Treatment with immune checkpoint inhibitors was used in the first-line setting in 4 patients (7%), in the second-line setting in 32 patients (56%) and in the third-line setting or more in 21 patients (37%). With a median follow-up of 12 months (95% confidence interval [CI]: 9.9-21.0), the median TTF was 3.1 months (95% CI: 2.7-5.0). Among the 55 patients evaluable for ORR, best response was complete response/partial response in 6 patients (11%), stable disease in 18 patients (33%) and progressive disease in 31 patients (56%). The median OS was 14.6 months (95% CI: 9.0- not reached). TRAEs of grade III-IV were noted in 6 patients (10%) leading to treatment discontinuation, and no grade V TRAEs were observed., Conclusion: PD-1/PD-L1 inhibitors exhibit limited activity as monotherapy in this pRCC population, which remains an unmet need. Our findings underline the need for further prospective clinical trials evaluating immune checkpoint inhibitor combinations in patients with pRCC., Competing Interests: Conflict of interest statement M.G.-G. reports receiving honoraria from Ipsen, Janssen, Astellas Pharma; has served consultant or advisory role in Astellas Pharma, Janssen, Ipsen and MSD; reports receiving research funding from MSD, BMS, Janssen, Astra Zeneca, Pfizer and Roche and travel accommodation expenses from Amgen, MSD, Roche, Pfizer and Sanofi. B.B. has served consultant or advisory role in BMS; has been a member of the speaker's bureau of Pfizer and Ipsen; reports receiving research funding from Pfizer and BMS and travel and accommodation expenses from Pfizer. C.T. has served consulting or advisory role in BMS, Pfizer and Ipsen and reports receiving travel and accommodation expenses from Pfizer and Roche. C.C. has served consultant or advisory role in Pfizer, Novartis and BMS. P.B. has served consultant or advisory role in BMS, Pfizer, Roche, MSD, Ipsen, Novartis, and Sanofi and reports receiving honoraria from Astellas Pharma and travel and accommodation expenses from Amgen. S.N. reports receiving honoraria from Pfizer, Ipsen, BMS, EUSA Pharma and Novartis; research grant from Pfizer and travel expenses from BMS, Pfizer and Ipsen. D.B. has served consultant or advisory role in BMS, Ipsen and Pfizer and travel and accommodation expenses from Roche. O.H. reports receiving honoraria from BMS, AstraZeneca, Sanofi, Janssen and GSK and travel expense from Ipsen, Sanofi, Pfizer, Janssen and Astellas Pharma. L.G. has served consulting or advisory role in BMS, MSD, Novartis, Ipsen and Janssen. G.G. reports receiving travel expenses from BMS and Pfizer. A.T.-V. reports receiving honoraria from Pfizer, AstraZeneca, Sanofi, Janssen, Novartis, Ipsen, BMS andRoche; has served consultant or advisory role in Pfizer, AstraZeneca, Sanofi, Janssen, Novartis, Ipsen, BMS and Roche and reports receiving research funding from Pfizer and travel and accommodation expenses from BMS, Roche, Janssen and Pfizer. B.E. has served advisory role for BMS, Pfizer, Novartis, Roche, Ipsen, EUSA and Aveo and reports receiving travel grants from BMS and Pfizer and research grants from BMS, Novartis, Aveo and Pfizer. A.R. has served consultant or advisory role in Pfizer, BMS, AstraZeneca, Roche, MSD and Ipsen and reports receiving travel and accommodation expenses from Pfizer, BMS, AstraZeneca, Roche, MSD and Ipsen and institutional grant from Pfizer. L.A. has served consultant or advisory role in Pfizer, Novartis, BMS, Ipsen, Roche, MSD and AstraZeneca. M.de.V.-B., V.S., E.B., S.L., C.S. report no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Abiraterone acetate (abiraterone) combined with prednisone is a standard of care in metastatic castration-resistant prostate cancer. Recently, benefit in overall survival was reported in metastatic castration-sensitive prostate cancer also, and an extension of indication has been granted. Abiraterone is seldom associated with liver toxicity. The clinical management and the outcome of patients with transaminase increase while on abiraterone have not been described., Patients and Method: We identified 25 men with metastatic prostate cancer and liver function test disorders occurring while on abiraterone treatment from December 2009 to September 2017 in three oncology centres in France., Results: Forty-six liver disorder events occurred in 25 patients while on abiraterone treatment. The median age at liver function test increase was 67 (55-85) years. The incidence of aspartate aminotransférase (AST) (24 events) and that of alanine aminotransférase (ALT) (22 events) increases were similar. Liver toxicity was of grade 1, 2 and 3 (Common Terminology Criteria for Adverse Events. version 4) in 7 (32%), 6 (27%) and 9 (41%) patients for ALT, and in 12 (50%), 6 (25%) and 6 (25%) for AST, respectively. The median time from abiraterone initiation to the detection of liver toxicity was 7.1 (4-95) weeks. The median time from highest ALT/AST increase to normalisation was 6.2 [2-14] weeks. In 13 patients (52%), liver tests spontaneously returned to baseline values, while abiraterone was continued at full dose., Conclusion: Liver function test increase is a rare event that typically occurs within the first two months on abiraterone. Most patients experience normalisation of the tests, either spontaneously or after dose reduction/discontinuation., Competing Interests: Conflict of interest statement E.C. declared having received personal fees from Ipsen, Sanofi, BMS and Pfizer. G.B. declared having received consulting fees from Janssen-Cilag and Sanofi. Y.L. has received honoraria from Sanofi, Janssen, MSD, Roche, BMS, AstraZeneca, Astellas and Seattle Genetics; has received grants from Sanofi, Janssen and MSD and has been an investigator in trials sponsored by MSD, Roche, Astellas, Janssen, Nektar, BMS, Pfizer, Incyte, Clovis, AstraZeneca and Seattle Genetics. L.A. declared serving consulting or advisory role in Novartis, Amgen (Inst), Bristol-Myers Squibb, Bristol-Myers Squibb (Inst), Ipsen (Inst), Roche (Inst), Novartis (Inst), Pfizer (Inst), Astellas Pharma (Inst) and Merck (Inst). C.M. reported receiving grants and personal fees and is a principal investigator/co-principal investigator for Amgen, Astella, AstraZeneca, Bayer, BeiGene, BMS, Genentech, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion and Abbvie. J.A. has received grants and honoraria from AstraZeneca, Roche/Genentech, Novartis, Ipsen and Jansen. O.H. declared having received personal fees from IPSEN, Janssen, Bayer, BMS and Sanofi. S.C. declares serving a consultant role for Janssen, Roche and Merck; that he has received research funding from Astellas and Roche and that he has been beneficiant of travel support from Janssen, Roche and Astellas. K.F. declared having received fees for participation to advisory boards or lectures for Amgen, Astellas, Bayer, Janssen-Cilag, Orion and Sanofi. G.M., P.L. and E.C. declared no disclosure., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Receiving a diagnosis of cancer may be associated with increased risk of mental disorders. Yet, in this context, no factor predicts the onset of a mental disorder besides the diagnosis of cancer itself. If patients with a history of mental disorder are at particular risk is unknown., Methods: Data were derived from a large national sample of the US population. Face-to-face surveys were conducted on 36309 adults during 2012-2013 period. Data were used to examine the associations among the past-year prevalence of mental disorders (according to the Diagnostic and Statistical Manual of Mental Disorders-5), the treatment-seeking rates and a recent cancer diagnosis. Data were analysed according to the antecedents of mental disorder in participants and according the presence of a recent cancer diagnosis., Results: Participants recently diagnosed with cancer (n = 1300) were significantly at higher risk to present suicide attempt (adjusted odds ratio [AOR] = 3.52; 95% confidence interval [CI] = 1.23-10.04), post-traumatic stress disorder (AOR = 2.25; 95% CI = 1.71-2.96), bipolar disorder (AOR = 2.22; 95% CI = 1.46-3.38) and drug use disorder (AOR = 1.64; 95% CI = 1.13-3.39). The prevalence of most of the mental disorders considered was significantly higher for participants with a history of mental disorder compared with participants without such a history. Conversely, a recent diagnosis of cancer was not associated with significant differences in the incidence of mental disorders in participants with no history of mental disorder., Conclusions: Patients with a history of mental disorder receiving a cancer diagnosis are at high risk of relapse and should be closely monitored., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Abiraterone (ABI) is a major oral agent for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients but its systemic exposure is subject to a large inter-individual variability. We aimed to explore the relationship between ABI trough plasma concentration and prostate-specific antigen (PSA) response in mCRPC patients and to identify the critical determinants for its activity., Patients and Methods: This is a monocentric prospective observational study in mCRPC patients treated with ABI. The plasmatic concentration of ABI at steady state was measured using liquid chromatography with fluorescence detection. The primary objective was to study the relationship between mean ABI plasma exposure (ABI C min ) and 3-month PSA response., Results: From 2012 to 2016, 61 mCRPC patients were eligible for pharmacokinetic/pharmacodynamic assessment. Thirty-eight patients experienced PSA response (62%, [confidence interval {CI} 95% 50-78]). In univariate analysis, ABI C min was 1.5-fold higher in responders: 12.0 ng/mL (CI 95% 9.4-15.6) versus 8.0 ng/mL (CI 95% 5.8-11.6; P = 0.0015). In multivariate analysis, only ABI C min was independently associated with PSA response (odds ratio = 1.12 [CI 95% 1.01-1.25], P = 0.004). By receiver operating characteristic analysis, the optimal threshold for ABI C min was 8.4 ng/mL. Progression-free survival (PFS) was significantly higher in patients with ABI C min above 8.4 ng/mL (hazard ratio 0.55, [CI 95% 0.31-0.99], 12.2 [CI 95% 9.2-19.5] versus 7.4 [CI 95% 5.5-14.7] months otherwise, P = 0.044)., Conclusions: We showed that ABI trough concentration correlates with PSA response and PFS. Moreover, we could determine a cut-off value of plasmatic concentration for PSA response. Altogether, ABI concentration monitoring appears as a new approach to improve clinical outcome in mCPRC patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

When using molecularly targeted agents (MTAs), oncologists and patients face new and sometimes unexpected toxicities. Though ocular adverse events (OAEs) are not uncommon with chemotherapy, they are rarely severe or dose limiting. Ocular toxicity profile may differ with MTAs, indeed severe and dose limiting toxicities have been described with targeted therapies currently under investigation. Our study aimed to review OAEs experienced with MTAs approved in solid tumours. This review revealed that many OAEs, frequent and potentially severe, exist and concern most MTAs. The suggestion is prompt referral of patients with severe pain and/or visual impairment to the ophthalmologist since these symptoms can be associated with potentially severe OAE and need ophthalmic assessment. Oncologists must be aware of such events and their potential severity for better treatment and better diagnosis in daily practice as well as in clinical trials., (Copyright © 2013 Elsevier Ltd. All rights reserved.)