Meta-analysis of perioperative immunotherapy in renal cell carcinoma: Available, but the jury is still out.

Introduction: While surgical management of renal cell carcinoma (RCC) is curative for many patients, others may relapse and could benefit from adjuvant treatments. Immune checkpoint inhibitors (ICI) have been proposed as a potential adjuvant therapy for improving survival in these patients, but the benefit/risk ratio of ICI in the perioperative setting remains unclear.
Methods: A systematic review and a meta-analysis of phase III trials of perioperative ICI (anti PD1/PD-L1 alone or in combination with anti-CTLA4 agents) in RCC was conducted.
Results: The analysis included results from 4 phase III trials, comprising 3,407 patients. ICI did not show a significant increase in disease-free survival (Hazard Ratio [HR] 0.85; 95% confidence interval [CI] 0.69-1.04; p: 0.11) or overall survival [OS] (HR 0.73; 95% CI 0.40-1.34; p: 0.31). High-grade adverse events were more frequent in the immunotherapy arm (OR 2.65; 95% CI 1.53-4.59; p: <0.001), and high-grade treatment-related adverse events were 8 times more frequent in the experimental arm (OR: 8.07; 95% CI: 3.14-20.75; p: <0.001). Subgroup analyses showed statistically significant differences favoring the experimental arm in females (HR: 0.71; 95 CI 0.55-0.92; p: 0.009), in sarcomatoid differentiation (HR: 0.60 95% CI 0.41-0.89; p: 0.01), and PD-L1 positive tumors (HR HR: 0.74; 95% CI 0.61-0.90; p: 0.003). No significant effect was found in patients according to age, type of nephrectomy (radical vs. partial), and stage (M1 without evidence of disease vs. M0 patients).
Conclusion: Our comprehensive meta-analysis generally suggests that immunotherapy does not confer a survival advantage in the perioperative setting for RCC, with the exception of one positive study. While the overall results are not statistically significant, individual patient factors and other variables may play a role in determining who benefits from immunotherapy. Therefore, despite the mixed findings, immunotherapy may still be a viable treatment option for certain patients, and further studies are needed to determine which patient subgroups would be most likely to benefit.
Competing Interests: Declaration of Competing Interest This research did not receive additional support from an organization beyond the authors’ academic institutions. Guillermo de Velasco: GDV is supported by ISCIII-AES-2021 PI21/01922 Consulting and advisory services from Pfizer, Novartis, Bayer, Roche, Ipsen, Astellas Pharma, Bristol-Myers Squibb, MSD and Merck; research funding from Ipsen; and Honoraria, travel and accommodation expenses from Pfizer, Ipsen, Bristol-Myers-Squibb, Astellas Pharma and Roche; Daniel Castellano: Consulting or Advisory Role—Astellas Pharma; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol-Myers Squibb; Ipsen; Janssen Oncology; Lilly; MSD Oncology; Novartis; Pfizer; Pierre Fabre; Roche/Genentech; Sanofi; Roberto Iacovelli: Advisory Board member—Astellas, BMS, EISAI, IPSEN, Janssen, MSD, Novartis, Pfizer, Sanofi. Consultant for Astellas, EISAI, MSD, Pfizer; Laurence Albiges: Consulting/advisory role—BMS, Pfizer, Novartis, Sanofi, Amgen, Bristol-Myers Squibb, Bayer, and Cerulean; research funding—Pfizer and Novartis. Rest of authors including corresponding author confirm no other conflict of interest to disclose. The authors declare there are no patents to disclose. The authors declare there are not addition relationships or activities to declare.
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