Efficacy and safety of SABR/partial‑SABR combined with axitinib and toripalimab in recurrent or metastatic renal cell carcinoma: Preliminary results from a prospective phase 2 trial

The present study aimed to investigate the safety and efficacy of the combination of axitinib, toripalimab and stereotactic ablative body radiotherapy (SABR) in the treatment of recurrent or metastatic renal cell carcinoma (RCC). The present study was a single-center, prospective study in which all patients received a treatment regimen consisting of axitinib combined with toripalimab and comprehensive multi-lesion SABR. The primary endpoint was progression-free survival (PFS)1 (start of radiotherapy to first disease progression), while secondary endpoints included PFS2 (start of radiotherapy to second-line systemic treatment due to disease progression), overall survival (OS), local control, objective response rate (ORR) and disease control rate (DCR). Adverse events were assessed according to the Common Terminology Criteria for Adverse Events version 5.0. A total of 30 patients were enrolled, of whom 21 (70.0%) had clear cell carcinoma and 23 (76.7%) had oligometastatic disease. The median follow-up time was 17.8 months (range, 1.2-47.7 months). The overall ORR was 60.0%, and the DCR was 80.0%, with a DCR of 96.7% for the irradiated lesions and 83.3% for the non-irradicated lesions. The median PFS1 time was 20.3 months (95% CI, 5.2-35.4 months), and the median OS was 44.8 months (95% CI, 20.0-69.6 months), while the median PFS2 time was not reached. As of September 2024, 24 out of 30 patients remained alive, with 15 experiencing disease progression. Subgroup analysis revealed that PFS1 was significantly longer when radiotherapy was administered before treatment failure compared with after (28.6 vs. 6.9 months; P=0.014). Regarding adverse events, the most common were diarrhea and fatigue, with grade ≥3 adverse events occurring in 50.0% of patients. In conclusion, mid-term analysis results show that the combination therapy of axitinib, toripalimab and SABR has achieved satisfactory survival outcomes in patients with recurrent or metastatic RCC, with manageable adverse reactions. Long-term follow-up data are still needed for validation. The present trial was retrospectively <i>registered</i> at clinicaltrials.gov (registration no. NCT06889649; 03-03-2025).