AstraZeneca's Imfinzi Approved for NSCLC Perioperative Use

AstraZeneca’s Imfinzi (durvalumab) has been approved by the US Food and Drug Administration (FDA) for use in treating non-small cell lung cancer (NSCLC) in the perioperative stage. This approval follows the FDA's recent call for a revamp in lung cancer trial designs. The new approval allows Imfinzi to be used in combination with chemotherapy for patients with resectable early-stage NSCLC (stages IIA-IIIB) who do not have known mutations in the epidermal growth factor receptor (EGFR) or rearrangements in the anaplastic lymphoma kinase (ALK).

The term "perioperative" refers to the period surrounding surgery, including the time before, during, and after the procedure. The approval of Imfinzi in this setting is based on the results from the Phase III AEGEAN study (NCT03800134). The study demonstrated that the perioperative use of Imfinzi reduced the risk of cancer recurrence, progression, or death by 32% compared to chemotherapy alone. However, the study did not provide separate data for the pre-surgery and post-surgery phases, raising concerns about which part of the treatment was most effective.

During a meeting held on July 25, the FDA’s Oncologic Drugs Advisory Committee (ODAC) discussed the design of trials in the perioperative setting. The committee expressed concerns about the lack of differentiation between the phases of treatment in the AEGEAN study. The FDA had advised AstraZeneca to design the study in a way that would evaluate the pre-surgery and post-surgery phases individually, but the company did not follow this guidance. This omission made it difficult for the committee to fully understand the side effects and additional benefits of the treatment, potentially leading to what they described as "overtreatment" with immune checkpoint inhibitors (ICIs) in the perioperative setting.

Despite these concerns, the ODAC largely supported the approval of Imfinzi for this indication. The committee's deliberation concluded with an 11-0 vote in favor of changing how perioperative trials are conducted in the future, rather than opposing the approval of Imfinzi itself.

Imfinzi was first approved for the treatment of bladder cancer in 2017. Its label has since been expanded to include various indications such as unresectable NSCLC, small-cell lung cancer, metastatic NSCLC, and endometrial cancer. In 2023, Imfinzi generated $4.2 billion in sales. According to forecasts from GlobalData’s Pharma Intelligence Center, the drug is expected to achieve $6.6 billion in sales by 2030.

The approval of Imfinzi in the perioperative setting puts it in direct competition with MSD’s Keytruda (pembrolizumab), which received FDA approval in October 2023 for NSCLC in a similar perioperative context based on the Phase III KEYNOTE-671 study (NCT03425643). Keytruda, which is already approved for multiple cancer indications, is projected to reach $21.3 billion in sales by 2030.

In the announcement of the FDA approval, Dave Fredrickson, executive vice president of AstraZeneca's oncology business unit, emphasized the significance of this new indication. He stated that the approval of Imfinzi for resectable early-stage lung cancer builds on the drug's strong track record in changing clinical practice for unresectable Stage III disease.