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Professor Tony Mok from The Chinese University of Hong Kong (CUHK)’s Faculty of Medicine (CU Medicine) joined with international experts in lung cancer to investigate the effect of different immunotherapy drugs in combination with chemotherapy on metastatic non-small cell lung cancer (NSCLC). Through a randomised, open-label study, they found that combining immune drugs tremelimumab plus durvalumab with chemotherapy can significantly improve progression-free survival and overall survival, representing a potential new option in first-line metastatic NSCLC treatment. The findings have been published in the leading international medical journal Journal of Clinical Oncology. 

Combination of tremelimumab plus durvalumab with chemotherapy significantly improves treatment efficacy for metastatic NSCLC 

Lung cancer is one of the most common cancers in the world, accounting for 1.8 million deaths every year. According to the Hong Kong cancer registry, lung cancer is the leading cause of cancer deaths and the most common cancer in the city, with more than 5,000 new cases every year. NSCLC accounts for over 80% of all lung cancers. Using immunotherapy alongside chemotherapy has proved promising in some recent studies for patients with metastatic NSCLC.

The international research team recruited 1,013 patients from 142 sites in 18 countries to join a Phase 3 study that compared treatment outcomes of combined immuno- and chemotherapy versus chemotherapy alone. They were randomly assigned to three treatment arms: immune checkpoint inhibitors tremelimumab plus durvalumab with chemotherapy (T+D+CT arm); durvalumab with chemotherapy (D+CT arm); or chemotherapy only (CT arm). (Please refer to table 1 in the appendix for details of study design.)

Results showed that treatment outcomes were better for patients who received combined immunotherapy with chemotherapy. In particular, the T+D+CT arm showed significant improvement compared to patients who only received chemotherapy, with a doubling of their 12-month progression-free survival rate, and an increase by 50% in their 24-month overall survival rate. (Please refer to table 2 and 3 in the appendix for full data.)

Professor Tony Mok, Li Shu Fan Professor of Clinical Oncology and Chairman of CU Medicine’s Department of Clinical Oncology, said, “Our study provided a new treatment option for metastatic NSCLC patients. The use of tremelimumab alongside durvalumab with chemotherapy significantly improved progression-free survival and overall survival versus chemotherapy, without a clinically meaningful increase in tolerability burden. We are grateful to have obtained approval from the U.S. Food and Drug Administration to apply this new treatment regime for patients with metastatic NSCLC in the U.S.”

The PD-L1-negative subgroup has particular clinical relevance 

Immune checkpoint inhibitors are a standard first-line therapy for advanced or metastatic NSCLC with PD-L1 expression, known as anti PD-1 checkpoint inhibitors. Durvalumab is one of them. However, patients with PD-L1-low or PD-L1-negative tumours are less likely to respond to anti PD-1 therapy, underling the need for new therapeutic strategies with immunotherapy combinations.

Professor Mok added, “The addition of immune drug tremelimumab, an anti-cytotoxic T-lymphocyte-associated antigen 4, extended clinical benefits to patients with PD-L1-negative tumours. These patients appeared to make the greatest gains in survival outcomes from this new combined therapy.”