Immunotherapy Strategies After Immune Checkpoint Inhibitor Exposure in Renal Cell Carcinoma

Importance Immune checkpoint inhibitors have transformed the treatment landscape for metastatic renal cell carcinoma; however, the failure of first-line therapeutic strategies remains a considerable challenge. Currently, clinicians face various issues, such as managing cases in patients who progress during treatment or relapse after adjuvant immunotherapy. Observations This review evaluates different strategies for treating patients with advanced kidney cancer previously exposed to immunotherapy. Evidence from other malignant neoplasms suggests potential effectiveness for rechallenging with immune checkpoint inhibitors. The most important available data are presented, including retrospective, prospective, and randomized clinical trials, to explore the role of immunotherapy in patients with renal cell carcinoma who have experienced prior failure of immune checkpoint inhibitors. Conclusions and Relevance Although retrospective data suggest modest effectiveness of an immunotherapy rechallenge treatment, larger phase 3 trials failed to demonstrate substantial benefit in progression-free survival and overall survival. Currently, no randomized evidence supports the use of agents targeting conventional immune checkpoints in patients with renal cell carcinoma who have previously received immunotherapy.