Introduction: Immune checkpoint inhibitors (ICI) have been approved for front-line therapy in metastatic renal cell carcinoma (mRCC). However, progressive disease often occurs and subsequent therapies are needed. ICI rechallenge may be an option, but there is a lack of data regarding efficacy and prognostic factors. We assessed efficacy of ICI rechallenge and factors associated with better outcomes. Patients and Methods . This ambispective multicenter study included 45 mRCC patients rechallenged with nivolumab ± ipilimumab between 2014 and 2020. Primary endpoint was investigator-assessed best objective response rate (ORR) for ICI rechallenge (ICI-2). Factors associated with ICI-2 progression-free survival (PFS) were evaluated with multivariate Cox models.
Results: ORR was 51% ( n = 23) at first ICI therapy (ICI-1) and 16% ( n = 7) for ICI-2. Median PFS was 11.4 months (95% CI, 9.8-23.5) and 3.5 months (95% CI, 2.8-9.7), and median overall survival was not reached (NR) (95% CI, 37.8-NR) and 24 months (95% CI, 9.9-NR) for ICI-1 and ICI-2, respectively. Factors associated with poorer ICI-2 PFS were a high number of metastatic sites, presence of liver metastases, use of an intervening treatment between ICI regimens, Eastern Cooperative Oncology Group performance status ≥2, and poor International Metastatic RCC Database Consortium score at ICI-2 start. Conversely, ICI-1 PFS >6 months was associated with better ICI-2 PFS. In multivariate analysis, there were only statistical trends toward better ICI-2 PFS in patients with ICI-1 PFS >6 months ( p =0.07) and toward poorer ICI-2 PFS in patients who received a treatment between ICI regimens ( p =0.07).
Conclusion: Rechallenge with nivolumab-based ICI has some efficacy in mRCC. We identified various prognostic factors in univariate analysis but only statistical trends in multivariate analysis. Our findings bring new evidence on ICI rechallenge and preliminary but unique data that may help clinicians to select patients who will benefit from this strategy.
Competing Interests: Charles Vauchier, Lucia Carril-Ajuria, Thomas Ryckewaert, Zahra Castel-Ajgal, Mostefa Bennamoun, Luca Campedel, Laurence Crouzet, and Jean-François Berdah have nothing to disclose. Edouard Auclin has received honoraria from Sanofi/Genzyme and travel and accommodations expenses from Mundipharma and has other relationships with Lilly Oncology. Philippe Barthélémy has received honoraria from Astellas Pharma and EUSA Pharma, as well as consulting and advisory fees from Amgen, Bristol-Myers Squibb, Ipsen, Janssen-Cilag, MSD Oncology, Novartis, Pfizer, and Roche. Delphine Borchiellini has received consulting and advisory fees from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen-Cilag, MSD Oncology, Novartis, Pfizer, and Sanofi; research funding from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Exelixis, Infinity Pharmaceuticals, Janssen, MSD, and Roche; and travel and accommodations expenses from Bristol-Myers Squibb, Janssen, Pfizer, and Roche. Antoine Thiery-Vuillemin has received honoraria from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche/Genentech, and Sanofi; consulting and advisory fees from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche, and Sanofi; research funding from Pfizer; and travel and accommodations expenses from AstraZeneca, Bristol-Myers Squibb, Janssen, MSD, Pfizer, and Roche. Elodie Coquan has an immediate family member employed by Sanofi and has received consulting and advisory fees from Ipsen, MSD, and Sanofi; research funding from Janssen; and travel and accommodations expenses from Bristol-Myers Squibb. Christine Chevreau has received consulting and advisory fees from Bristol-Myers Squibb, Ipsen, Novartis, and Pfizer, as well as travel and accommodation expenses from AstraZeneca, Bristol-Myers Squibb, MSD Oncology, and Pfizer/Ipsen. Raffaele Ratta has received consulting and advisory fees from Astellas Pharma and Pfizer, as well as travel and accommodation expenses from Astellas Pharma and Pfizer. Aude Fléchon has received honoraria from Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Ipsen, Janssen-Cilag, MSD Oncology, Pfizer, Roche/Genentech, and Sanofi/Aventis, as well as travel and accommodation expenses from Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Ipsen, Janssen-Cilag, MSD Oncology, Pfizer, Roche/Genentech, and Sanofi/Aventis. Felix Lefort has received travel and accommodation expenses from Ipsen and Roche. Laurence Albiges has received consulting and advisory fees from Amgen, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Corvus Pharmaceuticals, Exelixis, Ipsen, Janssen, Merck, MSD, Novartis, Peloton therapeutics, Pfizer, and Roche; research funding from Bristol-Myers Squibb; and travel and accommodation expenses from Bristol-Myers Squibb and MSD. Marine Gross-Goupil has received consulting and advisory fees from Amgen, Astellas, Medivation, AstraZeneca, Bayer/Onyx, Bristol-Myers Squibb, Ipsen, Janssen-Cilag, MSD Oncology, Pfizer, Roche, and Sanofi; research funding from AstraZeneca, Ipsen, Janssen-Cilag, Merck, MSD Oncology, Pfizer, and Roche; and travel and accommodation expenses from Astellas Pharma, AstraZeneca, Ipsen, Janssen-Cilag, Pfizer, and Roche. Yann-Alexandre Vano has received consulting and advisory fees from Astellas, Bristol-Myers Squibb, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, Roche, and Sanofi. Constance Thibault has received honoraria from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Janssen, Merck, MSD, Pfizer, and Sanofi; consulting and advisory fees from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Janssen, Merck, MSD, Pfizer, and Sanofi; research funding from AstraZeneca; and travel and accommodation expenses from Ipsen, Merck, and Pfizer. Stéphane Oudard has received honoraria from Astellas Pharma, Bayer, Bristol-Myers Squibb, Eisai, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, Roche/Genentech, and Sanofi; consulting and advisory fees from Astellas Pharma, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Ipsen, Janssen, Merck, MSD Oncology, Novartis, Pfizer, Roche, Roche, and Sanofi; research funding from Ipsen and Sanofi; and travel and accommodation expenses from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Merck, MSD Oncology, Novartis, Pfizer, and Roche.
(Copyright © 2022 Charles Vauchier et al.)