The combination of benmelstobart (TQB2450) and anlotinib (AL3818) has demonstrated superior clinical outcomes compared to sunitinib in the first-line treatment of advanced renal cell carcinoma (RCC). These findings from the phase 3 ETER100 trial (NCT04523272) were presented at the 2024 European Society for Medical Oncology (ESMO) Congress, potentially marking a new standard of care for this patient population.
The study revealed that patients receiving the combination therapy (n = 264) achieved a median progression-free survival (PFS) of 18.96 months (95% CI, 15.34-22.83) as assessed by blinded independent central review (BICR), compared to 9.76 months (95% CI, 8.38-12.42) in the sunitinib arm (n = 263; HR, 0.53; 95% CI, 0.42-0.67; P < .0001). The median overall survival (OS) was not estimable in either arm (HR, 0.66; 95% CI, 0.48-0.92; P = .0673). The overall response rates (ORR) by BICR were 71.6% in the combination arm and 25.1% in the sunitinib arm; 1.1% of patients in the combination arm achieved a complete response.
ETER100 Trial Design
The ETER100 trial was a multicenter, parallel-controlled study involving patients with locally advanced or metastatic clear cell RCC who had not received prior systemic antitumor therapy. Eligible patients were aged 18 to 80 years, had an ECOG performance status of 1 or less, and had at least one measurable lesion per RECIST 1.1 criteria. Patients with prior exposure to VEGFR-directed TKIs or immune checkpoint inhibitors were excluded.
Participants were randomized 1:1 to receive either anlotinib 12 mg daily on days 1-14 every 3 weeks plus benmelstobart 1200 mg on day 1 every 3 weeks, or sunitinib 50 mg daily on days 1-28 every 6 weeks. Stratification was based on IMDC risk group (favorable, intermediate, or poor). Treatment continued until disease progression or intolerable toxicity.
The primary endpoint was PFS by BICR per RECIST 1.1 criteria. Secondary endpoints included investigator-assessed PFS, OS, ORR, disease control rate, duration of response, and safety.
Baseline characteristics were well-balanced between the two arms. The median age in the combination arm was 60.5 years (range, 54.0-67.0) versus 59.0 years (range, 54.0-67.0) in the sunitinib arm. The majority of patients were male, had an ECOG performance status of 1, had IMDC intermediate-risk disease, and had undergone a prior nephrectomy.
Subgroup Analysis and Safety
Subgroup analysis indicated that the PFS benefit with anlotinib plus benmelstobart was consistent across all subgroups, with notable benefits observed in patients with sarcomatoid differentiation (HR, 0.33; 95% CI, 0.08-1.26) and liver metastasis (HR, 0.44; 95% CI, 0.23-0.85).
Both arms experienced high rates of treatment-emergent adverse events (TEAEs). Any-grade TEAEs occurred in 99.24% of patients in both arms, while grade 3 or higher TEAEs were observed in 75.00% and 74.62% of the combination and sunitinib arms, respectively. Serious adverse events were more frequent in the combination arm (38.64%) compared to the sunitinib arm (28.03%). Immune-related adverse events were reported in 33.33% of patients in the combination arm.
According to Dr. Xinan Sheng from Peking University Cancer Hospital and Institute, the combination of benmelstobart and anlotinib offers superior clinical outcomes with a manageable safety profile, potentially establishing it as a new first-line treatment option for advanced RCC.
