First-line benmelstobart plus anlotinib versus sunitinib in advanced renal cell carcinoma: Subgroup analysis from the phase 3 ETER100 trial.

4536 Background: Dual immune checkpoint inhibitors (ICIs) or ICIs plus VEGF-directed therapies, have been approved as first-line treatment in patients (pts) with advanced renal cell carcinoma (RCC). The phase 3 ETER100 trial showed that benmelstobart (PD-L1 blockade) plus anlotinib improved the progression-free survival (PFS) (19.0 months 9.8 months) and objective response rate (ORR) (71.6% vs 25.1%) of advanced clear cell RCC (ccRCC) pts significantly. Pts with factors, such as intermediate-poor International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk, liver metastasis, or bone metastasis were considered to have a poor prognosis. Here we report PFS and ORR in clinically relevant subgroups. Methods: ETER100 (NCT04523272) was a multicentre, randomised, open-label, controlled phase 3 trial conducted at 37 sites in China. Eligible patients were randomly assigned in a 1:1 ratio using stratified block randomisation to receive benmelstobart plus anlotinib or sunitinib. Randomisation was stratified according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk (favourable [score of 0], intermediate [score of 1-2], or poor risk [score of 3-6]). PFS analyses of clinically relevant subgroups were assessed using Kaplan-Meier method and the 95% CIs of response rate were calculated with the Clopper-Pearson method. Results: Overall, 527 pts received the trial treatments (264 in the benmelstobart-anlotinib group and 263 in the sunitinib group) and were evaluated for efficacy. A total of 454 (86%) pts had intermediate-poor IMDC risk, 62 (12%) pts had liver metastasis and 111(21%) had bone metastasis. Data cutoff for the interim analysis occurred on January 31, 2024. The median follow-up was 22.8 months. Benmelstobart plus anlotinib significantly improved PFS of subgroups with intermediate-poor IMDC risk (17.0 months [95% CI 14.0-20.1] vs 9.7 months [8.0-11.3], HR 0.55, 95% CI 0.43-0.72; p < 0.0001), liver metastasis (11.9 months [95% CI 5.8-NE] vs 5.4 months [1.5-6.7], HR 0.44, 95% CI 0.23-0.85; p < 0.0121), or bone metastasis (19.5 months [95% CI 16.5-27.2] vs 8.3 months [4.2-19.8], HR 0.52, 95% CI 0.30-0.89; p < 0.0154). ORR of benmelstobart-anlotinib group was significantly higher in the subgroups with intermediate-poor IMDC risk (70.0% [95%CI, 63.6- 75.9] vs 21.6% [16.4-27.5]), liver metastasis (60.0% [95%CI, 42.1-76.1] vs 7.4% [0.9-24.3]) and bone metastasis (63.2% [95%CI, 49.3-75.6] vs 16.7% [7.9-29.3]). Conclusions: The RCC pts with a poor prognosis such as intermediate-poor IMDC risk, liver metastasis and bone metastasis could significantly benefit from benmelstobart plus anlotinib. Clinical trial information: NCT04523272 .