Durvalumab in combination with platinum-based chemotherapy as neoadjuvant treatment, followed by durvalumab as monotherapy after surgery, has received approval from Swissmedic for the treatment of adult patients with resectable NSCLC (tumours ≥4 cm and/or positive lymph node involvement) without known mutations of the epidermal growth factor receptor (EGFR) or rearrangements of anaplastic lymphoma kinase (ALK).
This approval follows a planned interim analysis of the placebo-controlled Phase III AEGEAN study, a randomized, double-blind, multicenter study evaluating durvalumab as a perioperative treatment for patients with resectable NSCLC at stages IIA-IIIB irrespective of PD-L1 expression. In the study, 802 patients were randomized to receive a fixed dose of 1500 mg durvalumab plus chemotherapy or placebo plus chemotherapy every three weeks for four cycles before surgery, followed by durvalumab or placebo every four weeks (for up to 12 cycles) after surgery. Patients with known EGFR or ALK genomic tumor aberrations were excluded from the primary efficacy analyses.
The study demonstrated that durvalumab, when combined with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery (referred to as perioperative treatment), significantly and clinically improved event-free survival (EFS) compared to neoadjuvant chemotherapy alone followed by surgery in early-stage (IIA-IIIB) patients with resectable NSCLC.
Kaplan–Meier of event-free survival among all patients who had undergone randomization without documented EGFR or ALK alterations. Adapted according to Heymach JV et al, 2023.
Adding durvalumab to neoadjuvant chemotherapy also improved pathological complete response and pathological response. The study will continue as planned to evaluate key secondary endpoints such as disease-free survival and overall survival.
In the study, however, 96.5% of patients receiving durvalumab and 94.7% receiving placebo experienced adverse events. During the neoadjuvant phase, these rates were 91.0% and 89.2%, respectively. Serious grade 3 or 4 adverse events occurred in 42.4% of the durvalumab group and 43.2% of the placebo group. Treatment-related adverse events led to discontinuation in 12.0% of the durvalumab group compared to 6.0% of the placebo group. Deaths possibly related to treatment were rare but slightly higher in the durvalumab group (1.7% vs. 0.5%). Finally, immune-mediated adverse events were more common with durvalumab, occurring in 23.7% of patients compared to 9.3% in the placebo group, with most being mild to moderate​.
References:
- swissmedicinfo.ch
- Heymach JV, et al. Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N Engl J Med. 2023;389(18):1672-1684.
FDA Approval
