Safety evaluation of immune-based combinations in patients with advanced renal cell carcinoma: a systematic review and meta-analysis

Introduction: Immune-based combinations, including nivolumab plus ipilimumab, pembrolizumab plus axitinib, and (at a lesser extent) avelumab plus axitinib, should be regarded among the new standards of care for first line therapy of metastatic renal cell carcinoma. Toxicity profiles are different among all these above combinations, as well as between them and targeted agents monotherapies, including sunitinib (i.e. the control arm of all the above studies). Areas covered: We performed a systematic review and meta-analysis with the aim to compare adverse events from immune-based combinations versus sunitinib monotherapy across four recent randomized controlled trials (CheckMate-214, Keynote-426, IMmotion-151, and JAVELIN Renal 101) of front-line treatment for metastatic renal cell carcinoma, with particular attention to those from the ipilimumab plus nivolumab combination. Expert opinion: Beyond efficacy and activity, the ipilimumab plus nivolumab combination appears feasible, being endowed by an acceptable safety profile, in line with that of the other available options for the treatment of metastatic RCC. The different patterns of toxicities emerging from this systematic review and meta-analysis need to be kept in mind while choosing the appropriate treatment for each individual patient. Furthermore, prevention, prompt identification, and treatment of immune-related adverse events remains an area to be improved.