A novel combination therapy involving benmelstobart, anlotinib, and chemotherapy has demonstrated promising efficacy in patients with advanced or metastatic esophageal cancer. The Phase II trial, conducted across five centers, enrolled 50 patients and showed a median progression-free survival (PFS) of 14.9 months (95% CI, 11.4-NE) and an estimated one-year PFS rate of 58.5% (95% CI, 41.9%-71.9%). These findings suggest a potential new first-line treatment option for this challenging cancer.
Efficacy Outcomes
The study reported an objective response rate (ORR) of 72.0% (95% CI, 57.5%-83.8%), with 10.0% achieving complete response (CR) and 62.0% achieving partial response (PR). Disease control was observed in 84.0% of patients (95% CI, 70.9%-92.8%). The median duration of response (DoR) was 16.2 months (95% CI, 10.2-NE). Notably, 90.0% of patients experienced a decrease in target lesion size from baseline. "These results are encouraging and warrant further investigation in larger, randomized trials," researchers noted.
Safety Profile
The safety analysis revealed that 92% of patients experienced any grade adverse events (AEs), with 78% experiencing grade ≥3 events. Common AEs included leukopenia (64%), neutropenia (58%), anemia (56%), and hypertension (52%). Treatment-related adverse events (TRAEs) were also frequent, with similar rates to AEs. Immune-related AEs (irAEs) occurred in 48% of patients, with only 6% experiencing grade ≥3 irAEs. Dose reductions of anlotinib or chemotherapy were required in 34% of patients due to AEs, and 6% discontinued treatment due to toxicity. Serious bleeding events were reported in 6% of patients, including one grade 5 intracranial hemorrhage.
Subgroup Analysis
Exploratory analyses based on PD-L1 CPS status indicated varying ORRs, with 100% (4/4) for patients with CPS ≥10 and 67.6% (23/34) for those with CPS <10. Patients without liver metastases exhibited significantly longer PFS (20.5 vs. 4.7 months; p<0.0001) and OS (NR vs. 6.3 months; p<0.0001) compared to those with liver metastases.
Study Details
The study enrolled patients with advanced or metastatic esophageal cancer between September 2021 and November 2023. The median age of patients was 64 years, and 52% had a PD-L1 CPS below 1. Patients received benmelstobart in combination with anlotinib and chemotherapy as a first-line treatment. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS), objective response rate (ORR), and safety.
