While immune checkpoint inhibitors (ICI) can lead to sustained responses in metastatic renal cell carcinoma (mRCC), the optimal duration of therapy remains unknown. We aimed to examine treatment-free survival (TFS) in objective responders who discontinued ICI and to explore factors that may impact objective response rate (ORR) and TFS. MEDLINE/PubMed, Embase, and the Cochrane Library were searched for prospective studies reporting individual outcomes after ICI discontinuation in patients with mRCC. Pooled ORR and TFS were estimated using random-effects meta-analyses, and associations between ICI regimen type or treatment line and ORR or TFS were evaluated. Sixteen cohorts comprising 1833 patients treated with ICI were included. The pooled ORR was 43% (95% CI 33% to 53%), and significant differences in summary estimates existed among patients who received ICI monotherapy (22%, 95% CI 18% to 26%), ICI plus a vascular endothelial growth factor (VEGF) pathway inhibitor (57%, 95% CI 48% to 65%), and dual ICI (40%, 95% CI 36% to 44%). Of 572 responders who had available data, 327 stopped ICI, with 86 (26%) continuing to respond off-treatment. Pooled TFS rates at 6 and 12 months were 35% (95% CI 20% to 50%) and 20% (95% CI 8% to 35%), respectively, and were highest for responders treated with dual ICI and lowest for those treated with ICI plus a VEGF pathway inhibitor. Thus, a subset of patients with mRCC who are treated with ICI-based therapy can have durable TFS after therapy discontinuation. Prospective clinical trials and biomarkers are needed to identify patients who can discontinue ICI therapy without compromising clinical outcomes.
Journal for immunotherapy of cancer. 2021 Oct [Epub]
Alice Tzeng, Tony H Tzeng, Moshe C Ornstein
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA., School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA., Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland, Ohio, USA .