The combination of benmelstobart, anlotinib, and chemotherapy may be effective at improving median progression-free survival and overall survival in patients with extensive-stage small cell lung cancer compared with placebo and chemotherapy, according to findings presented by Cheng et al at the International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer (Abstract OA01.03).
Background
Despite the potential of immunochemotherapy, patients with extensive-stage small cell lung cancer often experience limited long-term survival benefits. The complex microenvironment of the disease—characterized by immunosuppression, angiogenesis, and vascularization—may hinder treatment effectiveness.
Study Methods and Results
In the recent multicenter phase III trial, researchers randomly assigned 738 patients with first-line extensive-stage small cell lung cancer to receive either four cycles of the PD-L1 inhibitor benmelstobart, the tyrosine kinase inhibitor anlotinib, or placebo in combination with etoposide/carboplatin chemotherapy. They then assigned the patients to receive maintenance therapy with benmelstobart plus anlotinib, anlotinib alone, or placebo until disease progression or toxicity intolerance. The researchers sought to reprogram the tumor microenvironment and promote immune cell infiltration. They noted the primary endpoints of the study were overall survival and progression-free survival assessed by an independent review committee in the intention-to-treat population.
After a median follow-up of 14 months, the researchers found the patients who received the combination of benmelstobart, anlotinib, and chemotherapy demonstrated significant median progression-free survival (6.9 months vs 4.2 months), median overall survival (19.3 months vs 11.9 months), objective response rate (81.3% vs 66.8%), and duration of response (5.8 months vs 3.1 months) compared with those who received placebo and chemotherapy.
Additionally, the safety profile of the benmelstobart, anlotinib, and chemotherapy regimen was reported to be manageable and tolerable, with grade ≥ 3 treatment-related adverse events—including decreased neutrophil, platelet, and white blood cell counts—reported in 93.1% of the patients in the treatment arm. Immune-related adverse events were also reported in a subset of patients.
Conclusions
"These results from the phase III trial are extremely encouraging, as the combination of benmelstobart, anlotinib, and chemotherapy achieved historically long overall survival and progression-free survival in extensive-stage small cell lung cancer," highlighted lead study author Ying Cheng, MD, of the Jilin Cancer Hospital in China. "This treatment approach demonstrates a significant survival extension over chemotherapy alone and provides a tolerable safety profile,” she concluded.
