Real-world outcomes with nivolumab–ipilimumab in metastatic renal cell carcinoma by nephrectomy status: A single-center study.

e16546 Background: Following the results of the CARMENA trial, the role of cytoreductive nephrectomy in the era of targeted therapy has been substantially reconsidered. However, the relevance of nephrectomy with contemporary dual immune checkpoint therapy remains insufficiently defined. Materials medians with 95% confidence intervals are reported. Results: In the overall cohort, median PFS was 11.0 months (95% CI 6.15–15.86) and OS was 40.0 months (95% CI 24.88–55.12). Median PFS differed by nephrectomy status: 6.0 months (95% CI 3.0–8.0) in patients without prior nephrectomy (n = 42), 12.0 months (95% CI 6.8–17.1) after nephrectomy for localized disease (n = 71), and 23.0 months (95% CI 6.2–39.7) after nephrectomy in the metastatic setting (n = 41) (p = 0.005). Survival showed a similar pattern: median OS was 19.0 months (95% CI 4.5–33.5) in patients without nephrectomy, was not reached after nephrectomy for localized disease, and was 55.0 months after nephrectomy in the metastatic setting (95% CI not reached). Patients with lung-only metastases had superior survival compared with those with other metastatic patterns (PFS 23.0 vs 9.0 months, p = 0.038; OS not reached vs 29.0 months, p = 0.020). PFS was strongly stratified by best overall response: median PFS was not reached in patients achieving complete response (16.8%), 45.0 months (95% CI 23.21–66.79) in partial response (23.4%), 10.0 months (95% CI 7.99–12.01) in stable disease (34.3%), and 2.0 months (95% CI 1.61–2.39) in progressive disease (25.5%) (p < 0.001). PFS did not differ according to histology (clear-cell vs non–clear-cell, p = 0.327), presence of a sarcomatoid component (p = 0.820), visceral metastases (p = 0.871), or grade ≥3 adverse events (p = 0.112). Similarly, OS did not differ by sarcomatoid component (p = 0.932), visceral metastases (p = 0.852), or grade ≥3 adverse events (p = 0.275), although numerically longer OS was observed in patients without grade ≥3 adverse events (47.0 vs 37.0 months). Second-line median PFS was 10.0 months (95% CI 4.45–15.55) and did not differ according to post–IPI+NIVO therapy (immunotherapy vs targeted therapy vs immuno-targeted combinations; p = 0.702). Conclusions: Our real-world outcomes with ipilimumab–nivolumab are consistent with the long-term results of CheckMate-214. The survival advantage observed with prior or cytoreductive nephrectomy accords with real-world and meta-analytic evidence suggesting that selected patients may derive benefit from combining surgery with immunotherapy, albeit with inherent selection and timing biases.