FDA Advisory Committee reviewed Imfinzi for treatment of resectable non-small cell lung cancer based on AEGEAN Phase III trial results
The Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC) acknowledged that AstraZeneca’s Imfinzi (durvalumab) met the primary endpoint of event-free survival (EFS) in the treatment of resectable non-small cell lung cancer (NSCLC) based on the AEGEAN Phase III trial results with an overall tolerable safety profile. In the trial, adult patients with resectable early-stage (IIA-IIIB) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements were treated with Imfinzi in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery. The discussion noted that while the contribution by phase of neoadjuvant and adjuvant components of the perioperative regimen could not be clearly assigned based on the trial design, this is an important potential regimen for patients.
The FDA accepted the supplemental Biologics License Application (sBLA) in September 2023 for Imfinzi in this indication based on positive results from the pivotal AEGEAN trial, which were published in The New England Journal of Medicine in October 2023.
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, said: “The majority of patients with resectable lung cancer face recurrence of their disease even after surgery and neoadjuvant chemotherapy. The Committee acknowledged the potential to address this urgent unmet need with durvalumab both before and after surgery, which can significantly increase the time patients live without progression and recurrence events in this curative-intent setting.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The Committee’s discussion of the AEGEAN data highlighted the significant benefit delivered by this Imfinzi-based regimen for patients with resectable lung cancer. We are committed to working closely with the FDA to bring this novel immunotherapy option to patients that offers a flexible chemotherapy backbone.”
Results from a planned interim analysis of EFS from the AEGEAN trial showed a statistically significant and clinically meaningful 32% reduction in the risk of recurrence, progression events or death versus chemotherapy alone in patients treated with the Imfinzi-based regimen before and after surgery (32% data maturity; EFS hazard ratio of 0.68; 95% confidence interval [CI] 0.53-0.88; p=0.003902). In a final analysis of pathologic complete response (pCR), treatment with Imfinzi plus neoadjuvant chemotherapy before surgery resulted in a pCR rate of 17.2% versus 4.3% for patients treated with neoadjuvant chemotherapy alone (difference in pCR 13.0%; 95% CI 8.7-17.6).
Imfinzi was generally well tolerated, and no new safety signals were observed in the neoadjuvant and adjuvant settings. Further, adding Imfinzi to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not compromise patients’ ability to complete surgery versus chemotherapy alone.
The ODAC provides the FDA with independent, expert advice and recommendations on marketed and investigational medicines for use in the treatment of cancer. The FDA will consider the feedback as it reviews the submission and is not bound by the Committee’s recommendation.
Imfinzi is approved in Switzerland and the UK for the treatment of adults with resectable NSCLC in Stage II and III without known EGFR mutations or ALK rearrangements, based on the AEGEAN results. Regulatory applications for Imfinzi in this setting are also currently under review in the EU, China and several other countries.
Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiotherapy based on the PACIFIC Phase III trial.