Efficacy and safety of avelumab + axitinib vs sunitinib in patients (pts) with very favorable-risk advanced renal cell carcinoma (aRCC): Subgroup analysis from the JAVELIN Renal 101 trial.

560 Background: In the JAVELIN Renal 101 phase 3 trial, first-line (1L) treatment with avelumab + axitinib in pts with aRCC significantly prolonged progression-free survival (PFS) and increased the objective response rate (ORR) vs sunitinib, irrespective of International Metastatic RCC Database Consortium (IMDC) risk group or number of IMDC risk factors. In the final analysis, overall survival (OS) results favored avelumab + axitinib vs sunitinib but did not reach statistical significance. A previous study in pts with favorable risk within the IMDC dataset identified a very favorable-risk subgroup, defined as pts with time from primary diagnosis to systemic therapy ≥3 years, Karnofsky performance status >80, and no brain, liver, or bone metastasis. We report post hoc analyses in pts with very favorable-risk aRCC. Methods: In JAVELIN Renal 101 (NCT02684006), eligible pts with untreated aRCC (any IMDC score) were randomized 1:1 to receive avelumab + axitinib or sunitinib. In this exploratory analysis, PFS and ORR per investigator assessment (RECIST 1.1), OS, and safety were assessed in the subgroup with very favorable risk. Results: In the avelumab + axitinib (n=442) and sunitinib (n=444) arms, respectively, 30 (6.8%) and 36 (8.1%) pts had very favorable risk disease. Within these subgroups, median age was 61.0 and 63.5 years, 96.7% and 94.4% pts had previous nephrectomy, and 60.0% and 61.1% had positive PD-L1 status, respectively. Follow-up was ≥68 months in all pts (data cutoff: Aug 31, 2023). OS, PFS, and ORR data are shown in the Table. Subsequent anticancer drug treatments were received by 70.0% pts after avelumab + axitinib vs 75.0% after sunitinib, including a PD-(L)1 inhibitor in 33.3% vs 63.9%, respectively. In the avelumab + axitinib vs sunitinib arms, respectively, treatment-related adverse events of any grade occurred in 100% vs 97.2% pts, including grade ≥3 events in 73.3% vs 61.1%, and led to permanent discontinuation of all study drugs in 0% vs 16.7%. Conclusions: In post hoc analyses from the JAVELIN Renal 101 phase 3 trial, long-term efficacy benefits were observed with avelumab + axitinib vs sunitinib in the subset of pts with very favorable-risk aRCC, consistent with results in the overall population and favorable IMDC risk subgroup. Safety findings were similar to those of previous analyses. These results support the use of 1L avelumab + axitinib treatment in pts with very favorable-risk aRCC and suggest that a tailored treatment strategy may improve aRCC management in this population. Clinical trial information: NCT02684006 . Outcomes data. Avelumab + axitinib (n=30) Sunitinib (n=36) Hazard ratio (95% CI) OS, median (95% CI), months Not reached (72.1-NE) 69.1 (51.4-NE) 0.48 (0.21-1.09) PFS, median (95% CI), months 26.3 (18.2-31.8) 12.5 (11.1-26.3) 0.57 (0.30-1.08) ORR (95% CI), % 83.3 (65.3-94.4) 44.4 (27.9-61.9) – NE, not estimable.