FDA Approves Imfinzi for NSCLC Pre- and Post-Surgery Use

AstraZeneca has recently secured FDA approval for the use of its PD-L1 inhibitor, Imfinzi (durvalumab), in certain non-small-cell lung cancer (NSCLC) patients. This approval covers the drug's neoadjuvant and adjuvant use in combination with platinum-containing chemotherapy for patients who do not have EGFR or ALK mutations. The FDA's decision followed a meeting last month where an advisory committee reviewed the necessity of an additional trial to assess the distinct contributions of the neoadjuvant (pre-surgery) and adjuvant (post-surgery) treatment phases.

During the meeting, while many committee members supported the approval of Imfinzi for this setting, a unanimous vote called for a change in the design of future clinical studies for perioperative regimens in patients with resectable NSCLC. This debate centered on whether the perioperative treatment phase is essential. The Phase III AEGEAN study showed that Imfinzi combined with chemotherapy before and after surgery reduced the risk of disease recurrence or progression by 32%. However, these results were comparable to data from Bristol Myers Squibb’s CheckMate-816 study, which evaluated the PD-1 inhibitor Opdivo (nivolumab) solely in the neoadjuvant setting.

In 2022, Bristol Myers Squibb obtained US approval for Opdivo in this indication, which has since been widely adopted by oncologists. Key opinion leaders (KOLs) have suggested that even with Imfinzi's approval for both neoadjuvant and adjuvant use, many doctors might continue to prefer Opdivo. The reasons include the lack of a compelling difference between the two drugs and the additional treatment burden posed by AstraZeneca’s antibody.

Imfinzi’s approval was primarily based on survival and response data from the AEGEAN study. The trial involved 802 patients with Stage IIA-IIIB NSCLC who were randomized to receive either Imfinzi plus chemotherapy or a placebo plus chemotherapy for four cycles prior to surgery. Post-surgery, patients continued with either Imfinzi or placebo every four weeks. The results were promising: patients on the Imfinzi regimen did not reach median event-free survival (EFS), while those in the placebo arm had an EFS of 29.5 months. Additionally, the pathological complete response rate was 17% for Imfinzi compared to 4.3% for placebo.

Regarding safety, both the Imfinzi and placebo groups experienced similar rates of Grade 3-4 adverse events from any cause. The most common adverse reactions in patients receiving Imfinzi included anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash.

This regulatory win for AstraZeneca marks a significant development in the treatment landscape for NSCLC. However, the ongoing debate about the optimal design for clinical trials in perioperative regimens indicates that further research and discussions are necessary to refine treatment strategies for resectable NSCLC. The experience with Imfinzi and Opdivo highlights the complexities involved in introducing new therapeutic options and the importance of clear, differentiated benefits to ensure widespread clinical adoption.