Benmelstobart plus anlotinib improves PFS, ORR vs sunitinib in aRCC

The combination of benmelstobart (TQB2450) and anlotinib (AL3818) yielded a superior progression-free survival (PFS) and overall response rate (ORR) vs sunitinib (Sutent) in the first-line treatment of patients with advanced renal cell carcinoma (aRCC), according to interim data from the phase 3 ETER100 trial (NCT04523272) presented at the 2024 European Society for Medical Oncology Congress in Barcelona, Spain.¹

Treatment with benmelstobart plus anlotinib was generally well-tolerated, with no new safety signals observed with either individual agent.

At a median follow-up of 18.69 months, the median PFS by blinded independent central review (BICR) was 18.96 months (95% CI, 15.34-22.83) in the benmelstobart plus anlotinib arm vs 9.76 months (95% CI, 8.38-12.42) in the sunitinib arm (HR, 0.53; 95% CI, 0.42-0.67; P < .0001), translating to a 47% reduction in the risk of progression or death. In total, 128/264 experienced a PFS event in the combination arm vs 145/263 in the sunitinib arm.

Further, the overall response rate was 71.6% in the benmelstobart plus anlotinib cohort compared with 25.1% in the sunitinib cohort (P < .001). In the combination arm, this consisted of a complete response in 1.1% of patients and a partial response in 70.5% of patients. In the sunitinib arm, all patients included in the ORR achieved a partial response.

At the time of data report, the overall survival (OS) data were not yet mature, with the median OS not reached in either arm (HR, 0.66; 95% CI, 0.48-0.92; P = .0673). At data report, there were 64/264 OS events in the benmelstobart plus anlotinib cohort and 80/263 OS events in the sunitinib cohort.

Treatment with benmelstobart plus anlotinib was generally well-tolerated, with no new safety signals observed with either individual agent.

Treatment-emergent adverse events (TEAEs) of grade 3 or higher occurred in 75% of patients in the benmelstobart plus anlotinib arm and 74.62% of patients in the sunitinib arm. Serious AEs were experienced by 38.64% of patients in the combination cohort vs 28.03% in the sunitinib cohort. Discontinuation of treatment due to AEs occurred in 12.5% of patients in the benmelstobart plus anlotinib arm vs 6.44% of patients in the sunitinib arm.

In total, the open-label, multicenter, phase 3 ETER100 trial included 531 adult patients with aRCC who were randomly assigned 1:1 to receive benmelstobart 1200 mg intravenously once every 3 weeks plus anlotinib 12 mg orally once daily with 2 weeks on, 1 week off (n = 266) or to sunitinib 50 mg orally once daily with 4 weeks on, 2 weeks off (n = 265). Patients were treated until disease progression or intolerable toxicity.

The trial enrolled patients across clinical trial sites in China.² Baseline characteristics were well-balanced between both arms. The median age among all patients was 60 years (range, 54-67).

To be eligible for enrollment, patients needed to have locally advanced or metastatic clear cell RCC, no previous systemic antitumor therapy, an ECOG performance score of 0-1, and at least 1 measurable lesion per RECIST v1.1. A key exclusion criterion was prior exposure to any VEGFR-TKIs or immune checkpoint inhibitors.

The primary end point for the trial is PFS by BICR per RECIST v1.1. Secondary end points include PFS per the investigators, ORR, OS, duration of complete response, duration of response, and safety.

The authors concluded, “Benmelstobart plus anlotinib provided superior PFS and ORR compared with sunitinib and had manageable safety in [patients] with previously untreated advanced RCC. These results support the use of Benmelstobart plus anlotinib as a new first-line treatment for advanced RCC.”

Reference

1. Sheng X, Shen P, Qu W, et al. Anlotinib in combined with anti-PD-L1 antibody Benmelstobart (TQB2450) versus sunitinib in first-line treatment of advanced renal cell carcinoma (RCC): A randomized, open-label, phase III study (ETER100). Presented at: 2024 European Society for Medical Oncology Congress. Barcelona, Spain. September 13-17, 2024. Abstract LBA76. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2024_abstracts/LBA76.html.pdf

2. A study of TQB2450 injection combined with anlotinib hydrochloride capsule versus sunitinib in subjects with advanced renal cancer. ClinicalTrials.gov. Last updated September 10, 2020. Accessed September 19, 2024. https://clinicaltrials.gov/study/NCT04523272