First-line Immuno-Oncology Combination Therapies in Metastatic Renal-cell Carcinoma: Results from the International Metastatic Renal-cell Carcinoma Database Consortium

Background: In metastatic renal-cell carcinoma (mRCC), recent data have shown efficacy of first- line ipilimumab and nivolumab (ipi-nivo) as well as immuno-oncology (IO)/vascular endothelial growth factor (VEGF) inhibitor combinations. Comparative data between these strategies are limited. Objective: To compare the efficacy of ipi-nivo versus IO-VEGF (IOVE) combinations in mRCC, and describe practice patterns and effectiveness of second-line therapies. Design, setting, and participants: Using the International Metastatic Renal-cell Carcinoma Database Consortium (IMDC) dataset, patients treated with any first-line IOVE combination were compared with those treated with ipi-nivo. Intervention: All patients received first-line IO combination therapies. Outcome measurements and statistical analysis: First- and second-line response rates, time to treatment failure (TTF), time to next treatment (TNT), and overall survival (OS) were analysed. Hazard ratios were adjusted for IMDC risk factors. Resultsandlimitations: Intotal,113patientsreceivedIOVEcombinationsand75receivedipi-nivo. For IOVE combinations versus ipi-nivo, first-line response rates were 33% versus 40% (between- group difference 7%, 95% confidence interval [CI] –8% to 22%, p = 0.4), TTF was 14.3 versus 10.2 mo (p = 0.2), TNT was 19.7 versus 17.9 mo (p = 0.4), and median OS was immature but not statistically different (p = 0.17). Adjusted hazard ratios for TTF, TNT, and OS were 0.71 (95% CI 0.46–1.12, p = 0.14), 0.65 (95% CI 0.38–1.11, p = 0.11), and 1.74 (95% CI 0.82–3.68, p = 0.14), respectively. Sixty-four (34%) patients received second-line treatment. In patients receiving subsequent VEGF-based therapy, second-line response rates were lower in the IOVE cohort than in the ipi-nivo cohort (15% vs 45%; between-group difference 30%, 95% CI 3–57%, p= 0.04; n=40), though second-line TTF was not significantly different (3.7 vs 5.4 mo; p = 0.4; n = 55). Limitations include the study’s retrospective design and sample size. Conclusions: There were no significant differences in first-line outcomes between IOVE combinations and ipi-nivo. Most patients received VEGF-based therapy in the second line.