Imfinzi Shows Significant Survival Benefit in Phase 3 Trial for Non-Small Cell Lung Cancer

AstraZeneca’s durvalumab (Imfinzi) and tremelimumab showed clinically meaningful and statistically significant improvements in overall survival (OS) and progression-free survival (PFS) when added to platinum-based chemotherapy in the first-line treatment of stage IV non–small cell lung cancer (NSCLC) compared to chemotherapy alone.

Durvalumab is a monoclonal antibody that blocks programmed death-ligand 1 (PD-L1), programmed cell death protein 1, and CD80 from interacting and releasing immune response inhibitors.

“The POSEIDON data offer patients further benefit from Imfinzi and are an important validation of our development strategy to explore novel combinations. Adding a short course of tremelimumab to Imfinzi for those patients already receiving chemotherapy, reduced the risk of cancer progressing or death by 28% compared to chemotherapy alone” Susan Galbraith, AstraZeneca executive vice president, Oncology R&D, said in a press release. “The results also showed the significant survival improvement did not compromise tolerability in the first-line treatment of patients with metastatic non-small cell lung cancer. We look forward to discussing these data with regulatory authorities.”

Results from POSEIDON, a randomized open label, phase 3 trial, showed that patients administered 5 cycles of tremelimumab plus durvalumab and chemotherapy over 16 weeks experienced a 23% reduction in the risk of death compared with various chemotherapy options (hazard ratio [HR] of 0.77; 95% CI 0.65-0.92; p=0.00304).

The results showed that median OS was 14.0 months with the durvalumab combination compared with 11.7 months for chemotherapy. Further, approximately 33% of patients were alive at 2 years compared with 22% in the chemotherapy along cohort.

The durvalumab combination was also found to reduce the risk of disease progression or death by 28% compared to chemotherapy alone (HR 0.72; 95% CI 0.60-0.86; p=0.00031) with a median PFS of 6.2 months compared with 4.8 months with chemotherapy alone.

The safety profile of durvalumab was consistent with the profiles of the individual medications and nothing new was identified, according to the study.

During the trial, 51.8% of patients treated durvalumab, tremelimumab, and chemotherapyexperienced grade 3 or 4 treatment-related adverse events (TRAEs) compared with 44.6% of patients treated with durvalumabplus chemotherapy, and 44.4% in the chemotherapy alone cohort. TRAEs caused discontinuation of treatment in 15.5% of patients treated with durvalumab, tremelimumab, and chemotherapy, versus 14.1% of patients treated with durvalumab plus chemotherapy, and 9.9% for chemotherapy alone.

“New combinations are increasingly important in addressing the remaining unmet needs that impact patients with metastatic non-small cell lung cancer—especially combinations that have the potential to improve efficacy in patients with lower PD-L1 expression and deliver the long-term survival benefits that have been observed with CTLA-4 inhibition,” Melissa Johnson, MD, director of the Lung Cancer Research program at Sarah Cannon Research Institute, and medical oncologist with Tennessee Oncology, PLLC in Nashville, Tennessee, said in a press release. The results of POSEIDON confirm that tremelimumab added to Imfinzi and chemotherapy is an effective, well-tolerated treatment in this setting.”

The drug combination is also being tested across all stages of lung cancer across NSCLC and small cell lung cancer, as well as bladder cancer and liver cancer.

Reference

IMFINZI and tremelimumab with chemotherapy improved progression-free survival by 28% and overall survival by 23% in 1st-line stage IV non-small cell lung cancer vs. chemotherapy. Business Wire. News release. September 9, 2021. Accessed September 9, 2021. https://www.businesswire.com/news/home/20210909005511/en/IMFINZI-and-tremelimumab-with-chemotherapy-improved-progression-free-survival-by-28-and-overall-survival-by-23-in-1st-line-Stage-IV-non-small-cell-lung-cancer-vs.-chemotherapy