FDA Approves Imfinzi for Resectable Non-Small Cell Lung Cancer
Key Insights
The FDA has approved Imfinzi (durvalumab) in combination with chemotherapy for adult patients with resectable early-stage NSCLC (search).
The approval was based on the AEGEAN trial, which showed a 32% reduction in the risk of recurrence, progression, or death versus chemotherapy alone.
Treatment with Imfinzi plus neoadjuvant chemotherapy resulted in a pathologic complete response rate of 17.2% compared to 4.3% with chemotherapy alone.
AstraZeneca's Imfinzi (durvalumab), in combination with chemotherapy, has received FDA approval for the treatment of adult patients with resectable early-stage (IIA-IIIB) non-small cell lung cancer (search) (NSCLC (search)) who do not have EGFR (search) mutations or ALK (search) rearrangements. This regimen involves Imfinzi in combination with neoadjuvant chemotherapy before surgery and adjuvant monotherapy after surgery.
The FDA's decision was based on the positive results of the pivotal AEGEAN trial, published in The New England Journal of Medicine. The trial demonstrated a statistically significant and clinically meaningful 32% reduction in the risk of recurrence, progression, or death compared to chemotherapy alone (EFS hazard ratio of 0.68; 95% CI 0.53-0.88; p=0.003902).
Pathologic Complete Response
The final analysis of pathologic complete response (pCR) showed that treatment with Imfinzi plus neoadjuvant chemotherapy before surgery resulted in a pCR rate of 17.2%, compared to 4.3% for patients treated with neoadjuvant chemotherapy alone (difference in pCR 13.0%; 95% CI 8.7-17.6).
Unmet Need in Resectable NSCLC
Approximately 25-30% of all patients with NSCLC (search) are diagnosed early enough to undergo surgery with curative intent. However, the majority of these patients will experience recurrence. Survival rates vary significantly by stage, with five-year survival rates ranging from 36-46% for Stage II disease to as low as 9% for Stage IIIB disease, highlighting a significant unmet medical need.
Expert Commentary
According to John V. Heymach, MD, PhD, Professor and Chair Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center in Houston, Texas, this approval represents "an important new treatment option that should become a backbone combination approach for patients with resectable non-small cell lung cancer (search), who have historically faced high rates of recurrence even after chemotherapy and surgery."
AEGEAN Trial Details
The AEGEAN trial is a randomized, double-blind, multi-center, placebo-controlled Phase III trial evaluating Imfinzi as perioperative treatment for patients with resectable Stage IIA-IIIB NSCLC (search). The trial included 802 patients randomized to receive either Imfinzi plus chemotherapy or placebo plus chemotherapy every three weeks for four cycles before surgery, followed by Imfinzi or placebo every four weeks (for up to 12 cycles) after surgery. The primary endpoints were pCR and EFS.
About Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein, blocking its interaction with PD-1 and CD80 proteins. This action counters the tumor's immune-evading tactics and releases the inhibition of immune responses. Imfinzi is also approved for unresectable Stage III NSCLC (search), extensive-stage SCLC, and metastatic NSCLC, as well as biliary tract cancer and hepatocellular carcinoma.
Safety Profile
Imfinzi was generally well-tolerated in the AEGEAN trial, with no new safety signals observed in the neoadjuvant and adjuvant settings. The addition of Imfinzi to neoadjuvant chemotherapy did not compromise patients' ability to complete surgery compared to chemotherapy alone.