Importance: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a lethal kidney cancer that has limited therapeutic options.
Objective: To evaluate the efficacy and safety of sintilimab plus axitinib for treatment of advanced FH-deficient RCC.
Design, setting, and participants: This phase 2 multicenter, open-label, single-arm nonrandomized clinical trial enrolled patients with pathologically confirmed, treatment-naive, advanced FH-deficient RCC and an Eastern Cooperative Oncology Group Performance Status of 0 to 2 from July 1, 2021, to August 29, 2023, across 8 institutions in China. The data cutoff date was December 1, 2024.
Intervention: Patients received sintilimab, 200 mg, intravenously every 3 weeks, combined with axitinib, 5 mg, orally twice daily, until disease progression, intolerable toxic effects, or withdrawal of consent.
Main outcomes and measures: The primary end points were objective response rate (ORR) via Response Evaluation Criteria in Solid Tumors, version 1.1, and progression-free survival (PFS). Secondary end points included safety, overall survival, disease control rate (proportion of patients with complete or partial response or stable disease for ≥6 months), duration of response, and exploratory genomic-associated outcomes.
Results: Of 52 patients screened for eligibility, 41 patients (median [range] age, 36 [18-75] years; 10 [24%] female) were enrolled. The median (range) duration of follow-up was 26.0 (0.7-41.6) months. Overall, ORR was 56% (23 patients; 95% CI, 40%-72%), with a median duration of response of not reached (NR; 95% CI, 23.3 months to NR). The disease control rate was 73% (30 patients). The median PFS was 19.8 months (95% CI, 10.9 months to NR). Patients with low somatic copy number alteration burden showed more favorable therapeutic outcomes. Thirteen patients (32%) experienced grade 3 or higher treatment-related adverse events, with the most frequent being hypertriglyceridemia in 3 (7%), rash in 2 (5%), and anemia in 2 (5%).
Conclusions and relevance: In this nonrandomized clinical trial, the combination of sintilimab and axitinib demonstrated encouraging ORR and PFS with manageable safety profile in patients with FH-deficient RCC. This combination therapy warrants further validation in a randomized clinical trial.
Trial registration: ClinicalTrials.gov Identifier: NCT04387500.