A multi-institution analysis of outcomes with first-line systemic therapy for 99 patients with metastatic chromophobe renal cell carcinoma.

4512 Background: Chromophobe renal cell carcinoma (ChRCC) represents ~5-10% of all RCCs. Given its rarity, there is limited clinical trial data to guide systemic therapy for metastatic disease. Phase 2 trials have demonstrated that targeted agents inhibiting vascular endothelial growth factor receptor and mammalian target of rapamycin have similar efficacy in ChRCC compared to conventional RCC. However, immune checkpoint inhibitor (IO) containing regimens appear less efficacious compared to other RCC subtypes. Importantly, these efforts have all enrolled < 30 ChRCC patients, and larger scale studies are needed. Methods: We conducted a retrospective study of patients with metastatic ChRCC seen at 3 academic centers. Baseline characteristics and treatment outcomes were obtained from EHR review. Patients were categorized into 4 treatment categories: 1) IO + targeted therapy doublets (e.g., lenvatinib plus pembrolizumab) 2) Pure IO monotherapy and doublets (e.g., ipilimumab plus nivolumab) 3) targeted therapy doublets (e.g., lenvatinib plus everolimus) and 4) targeted monotherapy (e.g., sunitinib). We calculated time to treatment failure (TTF) of first-line systemic therapy and overall survival (OS) by the Kaplan-Meier method. Median time-to-event was reported for each treatment category and categories compared with the log-rank test. Results: Ninety-nine patients with metastatic ChRCC treated with first-line systemic therapy were included; 62% were male, 44% had sarcomatoid features, and 33% had IMDC favorable risk. Outcomes with TTF and OS are summarized in the table below. Median TTF and 18-month OS rates were 5 months and 58% for the targeted monotherapy group, 15 months and 80% for the IO/targeted doublet group, 17 months and 65% for the targeted doublet group, and 7 months and 83% for the pure IO group. Treatment with any doublet containing a targeted agent compared to targeted monotherapy yielded a superior median TTF (15 vs 5 months, HR 0.48; 95% CI: 0.29, 0.80; p=0.005) and OS (56 vs 23 months, HR 0.56; 95% CI: 0.30, 1.04; p=0.07). Most treatment (64%) was discontinued due to progression; 25% due to toxicity. 11 patients had ongoing treatment at time of analysis. Conclusions: In this observational analysis, patients with targeted doublet regimens had a higher median TTF and OS compared to those receiving monotherapies. We continue to build on this dataset and plan to conduct progression free survival analysis. Table: see text