Real-world efficacy of first-line nivolumab plus ipilimumab and its practical predictive biomarkers in advanced renal cell carcinoma: First analysis from RENOIR study [KCSG GU22-13]

초록

Background: This study investigated real-world efficacy of 1st-line nivolumab plus ipilimumab (NI) and its clinicopathologic predictive biomarkers in patients with advanced renal cell carcinoma (aRCC). Methods: This study retrospectively analyzed 455 patients with aRCC who received 1st-line NI between 2018 and 2022 at 20 centers in Korea. Primary outcome was objective response rate (ORR). Secondary outcomes were progression-free survival (PFS), overall survival (OS) and identifying its practical clinicopathologic biomarkers. Results: The median age of the patients was 65 years (range, 31 to 89 years), and 77.8% were male. Most of patients were intermediate (n¼285, 62.6%) or poor (n¼160, 35.2%) International Metastatic RCC Database Consortium (IMDC) risk groups. ORR was 41.5% including 4.8% of complete response, and median duration of response was 8.4 months (range 0.2-50.4). Achievement of objective response was significantly associated to male (odd ratio, OR 2.0, P¼0.017), previous nephrectomy (OR 2.1, P¼0.001), and lung metastasis (OR 2.4, P¼0.001). With a median follow-up duration of 13.6 months (range 12.2-15.0), the median PFS and OS were 13.5 months (95% confidence interval [CI], 8.7-18.4) and 51.5 months (95% CI, 34.9-68.1), respectively. In multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 (vs. 2) (hazard ratio, HR 0.7, P¼0.073 and HR 0.5, P¼0.007), IMDC intermediate risk (vs. poor risk) (HR 0.7, P¼0.043 and HR 0.5, P¼0.002), and completion of 4 cycles of NI (vs. 1-3) (HR 0.3, P<0.001 and HR 0.3, P<0.001) were significantly associated with better PFS and OS. Although using antibiotics before the initiation of NI was significantly associated with shorter OS (HR 1.7, P¼0.014), durable responders showed significantly longer OS (HR 0.02, P¼0.001). Conclusions: First-line NI showed comparable real-world efficacy in Korean patients with aRCC. ECOG PS, IMDC risk, and completion of 4 cycles of NI might affect both PFS and OS. Although previous use of antibiotics might adversely affect OS, male gender, lung metastasis or prior nephrectomy might be practical predictors of objective response, which itself could predict better OS.