In an interim analysis of a Chinese phase III trial (ETER100) reported in The Lancet Oncology, Zhou et al found that the combination of the PD-L1 inhibitor benmelstobart and anlotinib improved progression-free survival vs sunitinib in the first-line treatment of advanced clear cell renal cell carcinoma.
Study Details
In the multicenter open-label trial, 527 patients (full analysis set) were randomly assigned between August 2020 and February 2023 to receive benmelstobart at 1,200 mg every 3 weeks plus anlotinib at 12 mg once daily for the first 2 weeks of a 3-week cycle (n = 263) or sunitinib at 50 mg once daily for the first 4 weeks of a 6-week cycle (n = 264) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival as assessed by blinded independent central review in the full analysis set.
Key Findings
As of data cutoff for the analysis (end of January 2024), the median follow-up was 22.8 months (interquartile range = 15.2–29.7 months).
In the full analysis set, median progression-free survival was 19.0 months (95% confidence interval [CI] = 15.3–22.8 months) with benmelstobart plus anlotinib vs 9.8 months (95% CI = 8.4–12.4 months) with sunitinib (hazard ratio [HR] = 0.53, 95% CI = 0.42–0.67, P < .0001); the rates at 12 and 24 months were 65% vs 44% and 42% vs 26%. In the per-protocol set of 254 vs 251 patients who received at least one cycle of protocol treatment, median progression-free survival was 19.0 months (95% CI = 16.5–22.8 months) vs 11.0 months (95% CI = 8.5–13.6 months; HR = 0.55, 95% CI = 0.43–0.70, P < .0001).
Overall survival data were not mature. The rates at 12 and 24 months were 90% vs 81% and 72% vs 68%.
Grade ≥ 3 treatment-related adverse events occurred in 67% of those given benmelstobart plus anlotinib vs 66% of those given sunitinib, most commonly hypertension (34% vs 21%). Serious treatment-related adverse events were reported in 24% vs 16% of patients. Treatment-related adverse events led to discontinuation of benmelstobart in 7% of patients, anlotinib in 8%, and sunitinib in 4%. Treatment-related deaths were reported in three patients given benmelstobart plus anlotinib (from cardiorespiratory arrest, unknown reason, and renal failure).
The investigators concluded: “Benmelstobart plus anlotinib improved progression-free survival compared with sunitinib among patients with previously untreated, advanced clear cell renal cell carcinoma. These findings suggest the potential of benmelstobart plus anlotinib as a treatment option for this population.”
Aiping Zhou, MD, of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Chia Tai Tianqing Pharmaceutical Group and CSCO Clinical Oncology Research Foundation. For full disclosures of all study authors, visit thelancet.com.
