Triple Combination for Small Cell Lung Cancer: The Best Results Yet

Lung cancer is the leading cause of cancer deaths worldwide, and advanced small cell lung cancer is a particularly treatment-resistant subtype. Its complex tumour microenvironment includes factors that can limit treatment effectiveness. New approaches that could extend life and improve quality of life are therefore an important research focus. In this context, Cheng and colleagues presented a study at the 2023 World Conference on Lung Cancer examining a combination with the potential to expand treatment options.

Study Details

In the multicentre phase III ETER701 trial presented at the conference, researchers randomly assigned 738 patients with advanced small cell lung cancer. Some received the PD-L1 inhibitor benmelstobart and the tyrosine kinase inhibitor anlotinib with etoposide/carboplatin chemotherapy. The comparison group received the same chemotherapy with placebo instead of benmelstobart and anlotinib, allowing assessment of the new combination. Initial treatment comprised 4 cycles.

After 4 treatment cycles, patients entered three maintenance groups until progression or unacceptable adverse effects: benmelstobart with anlotinib, anlotinib alone or placebo.

The researchers aimed to reprogramme the tumour microenvironment and promote immune-cell infiltration.

The primary endpoints were overall survival and progression-free survival.

How the New Medicines Work

Anlotinib is a tyrosine kinase inhibitor that suppresses tumour growth and metastasis by targeting several kinases essential to cancer-cell growth, proliferation and angiogenesis, or new blood vessel formation. It inhibits receptor tyrosine kinases including VEGFR, FGFR, PDGFR and c-Kit.

Anlotinib has not yet received US Food and Drug Administration (FDA) approval for any cancer, but is approved in China for non-small cell lung cancer and some other cancers.

Benmelstobart, a PD-L1 inhibitor, is an immunotherapy.

Study Findings

• Findings after a median follow-up of 14 months:
  • Median progression-free survival was 6.9 months with benmelstobart, anlotinib and chemotherapy, compared with 4.2 months with placebo and chemotherapy.
  • Median overall survival with benmelstobart, anlotinib and chemotherapy was 19.3 months, compared with 11.9 months with placebo and chemotherapy.
  • The objective response rate was 81.3% with the combination, compared with 66.8% with placebo and chemotherapy.
  • Median response duration was 5.8 months with the combination, compared with 3.1 months with placebo and chemotherapy.
• Treatment Safety:
  • The combination’s safety profile, including grade 3 or higher treatment-related adverse effects, was considered manageable and tolerable.
  • 93.1% of patients in the combination group experienced adverse effects such as reduced neutrophil, platelet and white blood cell counts.

Conclusion

These phase III results are extremely promising: benmelstobart, anlotinib and chemotherapy achieved the best survival results reported so far for first-line treatment of advanced small cell lung cancer.