Safety and efficacy of immune checkpoint inhibitors in advanced urological cancers with pre-existing autoimmune disorders: a retrospective international multicenter study.

BACKGROUND

There is limited experience regarding the safety and efficacy of checkpoint inhibitors (CPI) in patients with autoimmune disorders (AD) and advanced urological cancers as they are generally excluded from clinical trials due to risk of exacerbations.

METHODS

This multicenter retrospective cohort analysis of patients with advanced renal cell cancer (RCC) and urothelial cancer (UC) with pre-existing AD treated with CPI catalogued the incidence of AD exacerbations, new immune-related adverse events (irAEs) and clinical outcomes. Competing risk models estimated cumulative incidences of exacerbations and new irAEs at 3 and 6 months.

RESULTS

Of 106 patients with AD (58 RCC, 48 UC) from 10 centers, 35 (33%) had grade 1/2 clinically active AD of whom 10 (9%) required corticosteroids or immunomodulators at baseline. Exacerbations of pre-existing AD occurred in 38 (36%) patients with 17 (45%) requiring corticosteroids and 6 (16%) discontinuing CPI. New onset irAEs occurred in 40 (38%) patients with 22 (55%) requiring corticosteroids and 8 (20%) discontinuing CPI. Grade 3/4 events occurred in 6 (16%) of exacerbations and 13 (33%) of new irAEs. No treatment-related deaths occurred. Median follow-up was 15 months. For RCC, objective response rate (ORR) was 31% (95% CI 20% to 45%), median time to treatment failure (TTF) was 7 months (95% CI 4 to 10) and 12-month overall survival (OS) was 78% (95% CI 63% to 87%). For UC, ORR was 40% (95% CI 26% to 55%), median TTF was 5.0 months (95% CI 2.3 to 9.0) and 12-month OS was 63% (95% CI 47% to 76%).

CONCLUSIONS

Patients with RCC and UC with well-controlled AD can benefit from CPI with manageable toxicities that are consistent with what is expected of a non-AD population. Prospective study is warranted to comprehensively evaluate the benefits and safety of CPI in patients with AD.

Informations de copyright

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: NM-C reports support for research travel from Pfizer and Ipsen, and consulting fees for BMS and Bayer. AT reports advisory fee from Foundation medicine and research funding to institution from EMD Serono, Aravive, Bayer, Corvus, WindMil Therapeutics. BB received an unrestricted research grant from Bristol-Myers Squib and speakers' fee from Bristol-Myers Squib, Pfizer, Ipsen and Merck. EL reports research clinical trial funding from Bristol-Myers Squib, Exelixis, Pfizer, Merck, Calithera, Peloton, Genentech, Roche; and consultant fees from Calithera. YZ reports advisory board: Amgen, Roche Diagnostics, Novartis, Jansen, Eisai, Exelixis, Castle Bioscience, Array, Bayer and Pfizer. RM reports consulting fees for Bristol-Myers Squib, Dendreon, Exelixis, Jannsen, Novartis, Pfizer, Tempus; RM receives research funding from Pfizer and Bayer. SS reports consulting fees from Jannsen, and receives research funding from Genentech. AM reports advisory board fees from Seattle Genetics and Debiopharm Group and institution research funding from Acerta Pharma, Genentech, Roche, Merck, Novartis, Seattle Genetics, Acerta Pharma, Mirati Therapeutics and Bristol-Myers Squibb. MH reports consulting fees from AstraZeneca, Bayer, BMS, Exelixis FujiFilm, Genentech and Pfizer; speaking fees from Exelixis; and research funding from BMS, Clovis, Exelixis, Genentech, Merck and Pfizer. TC reports honoraria from AstraZeneca, Alexion, Sanofi/Aventis, Bayer, BMS, Cerulean, Eisai, Foundation Medicine, Heron Therapeutics, Exelixis, Genentech, Roche, Lilly, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN, Analysis Group, NCCN, Michael J. Hennessy (MJH) Associates (Healthcare Communications Company with several brands such as OnClive and PER), L-path, Kidney Cancer Journal, Clinical Care Options, Platform Q, Navinata Healthcare, Harborside Press, American Society of Medical Oncology, NEJM, Lancet Oncology; Consulting fees from AstraZeneca, Alexion, Sanofi/Aventis, Bayer, BMS, Cerulean, Eisai, Foundation Medicine, Exelixis, Heron therapeutics, Genentech, Roche, GlaxoSmithKline, Lilly, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN, Analysis Group; support for research travel from Part of Consulting, Advisory role and Honoraria; research funding (Institutional and personal) from AstraZeneca, Bayer, BMS, Cerulean, Eisai, Foundation Medicine, Exelixis, Ipsen, Tracon, Genentech, Roche, Roche Products Limited, GlaxoSmithKline, Lilly, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Corvus, Calithera, Analysis Group, Takeda. LH reports consulting fees from Genentech, Dendreon, Pfizer, Medivation/Astellas, Exelixis, Bayer, Kew Group, Corvus, Merck, Novartis, Michael J Hennessy Associates (Healthcare Communications Company and several brands such as OncLive and PER), Jounce, EMD Serono, Ology Medical Education; research funding from Bayer, Sotio, Bristol-Myers Squib, Merck, Takeda, Dendreon/Valient, Jannsen, Medivation/Astellas, Genentech, Pfizer, Endocyte (Novartis), and support for research travel from Bayer and Genentech.