Combination extends survival in extensive-stage small cell lung cancer
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Key takeaways:
- Benmelstobart plus anlotinib and chemotherapy extended OS and PFS compared with chemotherapy alone.
- The combination regimen had a tolerable safety profile.
The addition of benmelstobart and anlotinib to chemotherapy significantly improved median PFS and OS compared with chemotherapy alone among patients with extensive-stage small cell lung cancer, according to study results.
Findings from the phase 3 trial — presented at International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer — additionally suggest the combination regimen has a acceptable safety profile.
Rationale and methods
Immunochemotherapy has previously been shown to extend short-term OS among patients with extensive-stage small cell lung cancer. However, an unmet need remains in improving long-term survival in this patient population, study investigators noted.
“Limited benefit might [be] attribute[d] to the complicated small cell lung cancer microenvironment, which is characterized by immunosuppression, angiogenesis and vascularization,” Ying Cheng, MD, chief physician and director of Jilin Cancer Hospital in China, and colleagues wrote in their abstract. “Tumor microenvironment reprogramming and tumor vessel normalization could promote immune cell infiltration, obtaining synergistic effects with immunotherapy.”
Cheng and colleagues conducted a randomized phase 3 placebo-controlled study to assess the safety and efficacy of combining the investigational PD-L1 inhibitor, benmelstobart (TQB2450; Chia Tai Tianqing Pharmaceutical), with the antivascular agent anlotinib (Advenchen Laboratories, Jiangsu Chia-Tai Tianqing Pharmaceutical) plus standard chemotherapy in patients with extensive-stage small-cell lung cancer.
The multicenter study enrolled 738 patients randomly assigned in a 1:1:1 ratio to receive four, 21-day cycles of benmelstobart, anlotinib or placebo plus chemotherapy.
Researchers presented data comparing two of the study’s arms at World Conference on Lung Cancer, including 246 patients who received the combination regimen of benmelstobart, anlotinib and chemotherapy and 247 patients assigned placebo plus chemotherapy.
OS and independent-review committee-assessed PFS served as the study’s primary endpoints.
Findings
At a median follow-up of 14 months, results showed significantly longer median PFS (6.9 vs. 4.2 months; HR = 0.32; 95% CI, 0.26-0.41) and median OS (19.3 vs. 11.9 months; HR = 0.61; 95% CI, 0.47-0.79) with the combination regimen compared with chemotherapy alone.
Researchers additionally observed a higher objective response rate (81.3% vs. 66.8%) and longer duration of response (5.8 vs. 3.1 months) with the combination regimen compared with chemotherapy alone.
Most patients experienced grade 3 or higher treatment-related adverse events, including 93.1% assigned the combination regimen and 87% of those who received chemotherapy alone.
Common grade 3 or higher treatment-related adverse events included decreased neutrophil count, platelet count and white blood cell count among both treatment groups. Moreover, 42.7% of patients assigned the combination regimen vs. 19.1% assigned chemotherapy alone experienced any grade immune-related adverse events.
Implications
“These results from the phase 3 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,” Cheng said in an IASLC-issued press release. “This treatment approach demonstrates a significant survival extension over chemotherapy alone and provides a tolerable safety profile.”
References:
- Benmelstobart plus anlotinib and chemotherapy shows benefit for patients with extensive-stage small-cell lung cancer (press release). Available at: https://www.iaslc.org/iaslc-news/press-release/benmelstobart-plus-anlotinib-and-chemotherapy-shows-benefit-patients. Published Sept. 10, 2023. Accessed Sept. 14, 2023.
- Cheng Y, et al. Abstract OA01.03. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer; Sept. 9-12, 2023; Singapore.
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Cheng Y, et al. Abstract OA01.03. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer; Sept. 9-12, 2023; Singapore.
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