Combination Immunotherapy in First-Line Treatment of Advanced Kidney Cancer
Posted: Tuesday, December 18, 2018
According to a review by Saby George, MD, of the Roswell Park Comprehensive Cancer Center, Buffalo, New York, and colleagues, first-line treatment of advanced renal cell carcinoma is evolving. The efficacy of current standard-of-care regimens is limited, in large part due to anti-VEGF treatment resistance. To this end, several trials are ongoing to assess the safety and efficacy of immune checkpoint inhibitors, such as PD-1/PD-L1/CTLA-4 antibodies, in combination with or without standard therapies, such as the tyrosine kinase inhibitor sunitinib. The authors discussed the rationale, recent evidence, and foreseeable challenges with this strategy in JAMA Oncology.
“Evidence indicates that immunotherapy-based combination approaches will be an integral component of the first-line treatment for advanced renal cell carcinoma,” concluded the authors.
Two ongoing phase III studies were among those featured in this review. In CheckMate 214, after a median follow-up of 25.2 months, the combination of nivolumab and ipilimumab (PD-1 and CTLA-4 antibodies) yielded higher overall response rates (P < .001) and longer overall survival (P < .001) in treatment-naive patients with intermediate- or poor-risk renal cell carcinoma compared with patients who received sunitinib alone. In IMmotion151, the PD-1 antibody atezolizumab plus the VEGF inhibitor bevacizumab was associated with longer progression-free survival (P = .02) and a higher overall response rate in PD-L1–positive patients compared with sunitinib alone
Although safety data were limited, in both trials, toxicity was deemed acceptable. Immune checkpoint inhibitors were associated with immune-related adverse events; commonly affected were the gastrointestinal, endocrine, skin, and hepatic systems, but these agents may affect any organ system. Thus, the authors noted, “a multidisciplinary collaborative approach is strongly recommended for managing the diverse array of [immune-related adverse events] that may be encountered in clinical practice.”