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Multicenter Study
. 2020 Oct 1;6(10):1606-1610.
doi: 10.1001/jamaoncol.2020.2169.

Evaluation of the Safety and Efficacy of Immunotherapy Rechallenge in Patients With Renal Cell Carcinoma

Praful Ravi  1 , Charlene Mantia  2 , Christopher Su  3 , Karl Sorenson  4 , Dean Elhag  5 , Nityam Rathi  6 , Ziad Bakouny  1 , Neeraj Agarwal  6 , Yousef Zakharia  5 , Brian A Costello  4 , Rana R McKay  7 , Vivek Narayan  8 , Ajjai Alva  3 , Bradley A McGregor  1 , Xin Gao  9 , David F McDermott  2 , Toni K Choueiri  1
Affiliations
Multicenter Study

Evaluation of the Safety and Efficacy of Immunotherapy Rechallenge in Patients With Renal Cell Carcinoma

Praful Ravi et al. JAMA Oncol. .

Abstract

Importance: Several immune checkpoint inhibitors (ICIs) are approved for use in patients with metastatic renal cell carcinoma (mRCC), but the efficacy and safety of ICI rechallenge in mRCC is unknown.

Objective: To evaluate the safety and efficacy of ICI rechallenge in patients with mRCC.

Design, setting, and participants: This multicenter, retrospective cohort study included consecutive patients with mRCC from 9 institutions in the US who received at least 2 separate lines of ICI (ICI-1, ICI-2) between January 2012 and December 2019.

Exposure: Receipt of an ICI (anticytotoxic T-lymphocyte-associated protein 4, anti-programmed cell death protein 1, or anti-programmed cell death ligand 1), alone or in combination with other therapies, in at least 2 separate lines of therapy for mRCC.

Main outcomes and measures: Investigator-assessed best overall response and immune-related adverse events.

Results: A total of 69 patients were included. Median (range) age at diagnosis of mRCC was 61 (36-86) years. Of these, 50 were men and 19 were women. The most common therapies received at ICI-1 were single-agent ICI (n = 27 [39%]) or ICI in combination with targeted therapy (n = 29 [42%]), while at ICI-2, the most common therapies were single-agent ICI (n = 26 [38%]) or dual ICI (n = 22 [32%]). Most patients discontinued ICI-1 owing to disease progression (n = 50 [72%]) or toxic effects (n = 16 [23%]). The overall response rates at ICI-1 and ICI-2 were 37% and 23%, respectively. The likelihood of a response at ICI-2 was greatest among patients who had previously responded to ICI-1 (7 of 24 [29%]), although responses at ICI-2 were seen in those who had progressive disease as their best response following ICI-1 (3 of 14 [21%]) as well as in those who received single-agent ICI at ICI-2 (7 of 23 [30%]). Grade 3 or higher immune-related adverse events were seen in 18 patients (26%) and 11 patients (16%) at ICI-1 and ICI-2, respectively. There were no treatment-related deaths.

Conclusions and relevance: The findings of this multicenter cohort study suggest that ICI rechallenge in patients with mRCC may be safe and reasonably efficacious, with an overall response rate of 23%. Data from prospective studies are needed to validate these findings and determine the role of sequential ICI regimens in treatment of mRCC.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Bakouny reports nonfinancial support from Bristol Myers Squibb (BMS) and grants from Genentech/ImCore outside the submitted work. Dr Agarwal is a consultant for Astellas, AstraZeneca, Bristol-Myers Squibb, Bayer, Clovis, Eisai, Exelixis, EMD Serono, Ely Lilly and Company, Foundation Medicine, Genentech, Janssen, Merck, Novartis, Nektar, Pfizer, Pharmacyclics, and Seattle Genetics, and has received research funding to his institution from AstraZeneca, Bavarian Nordic, Bristol-Myers Squibb, Calithera, Celldex, Eisai, Exelixis, Genentech, GlaxoSmithKline, Immunomedics, Janssen, Medivation, Merck, NewLink Genetics, Novartis, Pfizer, Prometheus, Rexahn, Sanofi, Takeda, Tracon, Bayer, Clovis, EMD Serono, Ely Lilly and Company, Janssen, and Nektar. Dr Zakharia is on the advisory board for Amgen, Roche Diagnostics, Novartis, Janssen, Eisai, Exelixis, Castle Bioscience, Array, Bayer, Pfizer, Clovis, and EMD Serono; the data and safety monitoring committee of Janssen; and has received clinical trial support to his institution from NewLink Genetics, Pfizer, Exelixis, and Eisai. Dr McKay reports research funding from Bayer, Pfizer and Tempus; is on the advisory board of Bayer, Bristol-Myers Squibb, Exelixis, Janssen, Novartis, Pfizer, Sanofi, and Tempus; and is a consultant for Dendreon and Vividion. Dr Narayan reports grants from Pfizer, Bristol-Myers Squibb, Merck, and GlaxoSmithKline, and personal fees from Janssen, AstraZeneca, and EMD Serono. Dr Alva reports grants from Bristol-Myers Squibb, Merck, Celgene, Arcus Biosciences, Janssen, Novartis, Prometheus, Progenics, Astellas/Seattle Genetics, and AstraZeneca outside the submitted work, and is on the advisory board for Bristol-Myers Squibb, Merck, AstraZeneca, Pfizer/EMD Serono. Dr McGregor reports personal fees from Bristol-Myers Squibb, Eisai, Exelixis, Pfizer, Nektar, Seattle Genetics, AstraZeneca, Emd Serono, Bayer, Astellas, Genentech, and Jansen outside the submitted work. Dr McDermott reports grants and personal fees from Bristol-Myers Squibb outside the submitted work, and research support from Bristol-Myers Squibb, Merck, Genentech, Pfizer, Exelixis, X4 Pharma and Alkermes Inc. Dr Choueiri reports research funding (institutional and personal) from AstraZeneca, Alexion, Bayer, Bristol-Myers Squibb/ER Squibb and Sons LLC, Cerulean, Eisai, Foundation Medicine Inc, Exelixis, Ipsen, Tracon, Genentech, Roche, Roche Products Limited, F. Hoffmann-La Roche, GlaxoSmithKline, Eli Lilly and Company, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Corvus, Calithera, Analysis Group, Sanofi/Aventis, and Takeda; honoraria from AstraZeneca, Alexion, Sanofi/Aventis, Bayer, Bristol-Myers Squibb/ER Squibb and Sons LLC, Cerulean, Eisai, Foundation Medicine Inc, Exelixis, Genentech, Roche, Roche Products Limited, F. Hoffmann-La Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, UpToDate, National Comprehensive Cancer Network Analysis Group, National Comprehensive Cancer Network, Michael J. Hennessy Associates, Inc , Research to Practice, L-path, Kidney Cancer Journal, Clinical Care Options, Platform Q, Navinata Healthcare, Harborside Press, American Society of Medical Oncology, New England Journal of Medicine, Lancet Oncology, Heron Therapeutics, and Lilly Oncology; is a consultant/advisor for AstraZeneca, Alexion, Sanofi/Aventis, Bayer, Bristol-Myers Squibb/ER Squibb and Sons LLC, Cerulean, Eisai, Foundation Medicine Inc, Exelixis, Genentech, Heron Therapeutics, Eli Lilly and Company, Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, UpToDate, National Comprehensive Cancer Network Analysis Group, Pionyr, Tempest, and Lilly Ventures; and stock ownership in Pionyr and Tempest; reports present or past leadership roles as Director of Genitourinary Oncology Division at Dana-Farber Cancer Institute and past president of medical staff at Dana-Farber Cancer Institute, member of National Comprehensive Cancer Network Kidney panel and the GU Steering Committee, past chairman of the Kidney Cancer Association Medical and Scientific Steering Committee, KidneyCan Advisory board, and Kidney Cancer Research Summit co-chair; has patents pending: International Patent Application No. PCT/US2018/12209, and International Patent Application No. PCT/US2018/058430. No other disclosures were reported.

Figures

Figure.
Figure.. Responses to Immune Checkpoint Inhibitor Rechallenge (ICI-2) in Selected Patient Populations.
There were a total of 68 evaluable patients at first course of immune checkpoint inhibitor therapy (ICI-1) and 64 evaluable patients at ICI-2. PD indicates progressive disease; PR, partial response; SD, stable disease; TT, targeted therapy.
See this image and copyright information in PMC

Comment in

  • ICI rechallenge in mRCC.
    Killock D. Killock D. Nat Rev Clin Oncol. 2020 Sep;17(9):520. doi: 10.1038/s41571-020-0407-x. Nat Rev Clin Oncol. 2020. PMID: 32561866 No abstract available.

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