The approval was based on trial results which showed the regimen reduced the risk of recurrence, progression, or death by 32% versus neoadjuvant chemotherapy alone.

RT’s Three Key Takeaways:

  1. FDA Approval of Durvalumab for Early-Stage NSCLC: The FDA approved AstraZeneca’s Imfinzi (durvalumab) in combination with chemotherapy for treating resectable early-stage non-small cell lung cancer (NSCLC).
  2. Reduction in Recurrence and Progression: The approval was based on the AEGEAN trial, which showed that the durvalumab-based regimen reduced the risk of recurrence, progression, or death by 32% compared to chemotherapy alone.
  3. Enhanced Pathologic Complete Response Rate: The combination of Imfinzi with neoadjuvant chemotherapy before surgery resulted in a pathologic complete response rate of 17.2%, significantly higher than the 4.3% response rate with chemotherapy alone.

AstraZeneca’s Imfinzi (durvalumab) in combination with chemotherapy has been approved in the US for the treatment of adult patients with resectable early-stage (IIA-IIIB) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements. 

In this regimen, patients are treated with Imfinzi in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery.

The approval by the Food and Drug Administration (FDA) was based on positive results from the AEGEAN trial, which were published in The New England Journal of Medicine in October 2023. 

Clinical Trial Results and Impact on Recurrence

Results from a planned interim analysis of event-free survival 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.

In a final analysis of pathologic complete response, treatment with Imfinzi plus neoadjuvant chemotherapy before surgery resulted in a pathologic complete response rate of 17.2% versus 4.3% for patients treated with neoadjuvant chemotherapy alone.

Each year, there are an estimated 2.4 million people diagnosed with lung cancer globally, with approximately 235,000 new diagnoses expected in the US in 2024.1-2 Around 25-30% of all patients with NSCLC, the most common form of lung cancer, are diagnosed early enough to have surgery with curative intent.3-4 

High Unmet Medical Need and Expert Commentary

However, the majority of patients with resectable disease will develop recurrence, and only 36-46% of patients with Stage II disease will survive for five years.5-6 This decreases to 24% for patients with Stage IIIA disease and 9% for patients with Stage IIIB disease, reflecting a high unmet medical need.6

“This approval brings an important new treatment option that should become a backbone combination approach for patients with resectable non-small cell lung cancer, who have historically faced high rates of recurrence even after chemotherapy and surgery,” says John V. Heymach, MD, PhD, professor and chair of thoracic/head and neck medical oncology at The University of Texas MD Anderson Cancer Center, in a release. “When added both before and after surgery, durvalumab delivered a significant and meaningful improvement in outcomes in this curative-intent setting.”

Global Approvals and Future Outlook

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.

Imfinzi is also approved in the UK, Switzerland, and Taiwan (China) in this setting based on the AEGEAN results. Regulatory applications are also currently under review in the EU, China, and several other countries in this indication.

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.

References

  1. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf. Accessed Aug 2024.
  2. American Cancer Society. Key Statistics for Lung Cancer. Available at: https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html. Accessed Aug 2024.
  3. Cagle PT, et al. Lung Cancer Biomarkers: Present Status and Future Developments. Arch Pathol Lab Med. 2013;137(9):1191-8.
  4. Le Chevalier T. Adjuvant Chemotherapy for Resectable Non-Small-Cell Lung Cancer: Where is it Going? Ann Oncol. 2010;21(suppl 7):vii196-8.
  5. Pignon JP, et al. Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26(21):3552-9.
  6. Goldstraw P, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol. 2007;2(8):706-14.

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