CHMP Recommends Perioperative Durvalumab Regimen in Resectable NSCLC

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of durvalumab (Imfinzi) plus chemotherapy as neoadjuvant therapy, followed by durvalumab monotherapy in the adjuvant setting, for the treatment of adult patients with resectable non–small cell lung cancer (NSCLC) who are at high risk of recurrence and do not harbor EGFR mutations or ALK rearrangements.1

The recommendation was based on results from the phase 3 AEGEAN trial (NCT03800134), which evaluated durvalumab plus neoadjuvant platinum-based chemotherapy and adjuvant durvalumab monotherapy vs placebo plus neoadjuvant chemotherapy, followed by adjuvant placebo.2 Findings from the study published in The New England Journal of Medicine demonstrated in the first interim analysis that patients in the intent-to-treat population had significantly longer event-free survival (EFS) when treated in the durvalumab arm (n = 366) vs the placebo arm (n = 374; stratified HR, 0.68; 95% CI, 0.53-0.88; P = .004). The 12-month EFS rates were 73.4% (95% CI, 67.9%-78.1%) in the durvalumab arm vs 64.5% (95% CI, 58.8%-69.6%) in the placebo arm. At 24 months, the EFS rates were 63.3% (95% CI, 56.1%-69.6%) and 52.4% (95% CI, 45.4%-59.0%), respectively.

In the final analysis of pathological complete response (pCR) rate at a data cutoff of November 10, 2022, the pCR rate was 17.2% (95% CI, 13.5%-21.5%) for the durvalumab arm vs 4.3% (95% CI, 2.5%-6.9%) for the placebo arm.

“Adding perioperative durvalumab to neoadjuvant chemotherapy significantly improved outcomes for patients with resectable NSCLC, who experience high rates of recurrence and poor outcomes,” Martin Reck, head, Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Germany, stated in a news release.1 “Today’s recommendation marks an important step towards patients and their clinicians in Europe gaining access to an innovative treatment that should become a backbone combination approach in this curative-intent setting.”

Interim overall survival (OS) results from the study were presented at the 2024 IASLC World Conference on Lung Cancer and demonstrated that the durvalumab combination showed a favorable trend at 35% data maturity. The median OS was not reached vs 53.2 months with durvalumab vs placebo (HR, 0.89; 95% CI, 0.70-1.14). At the interim analysis, the OS data were not tested for statistical significance and will continue to be assessed as a secondary end point at the final analysis.

In August 2024, the FDA approved perioperative durvalumab plus chemotherapy for the treatment of patients with resectable NSCLC, which was based on efficacy data from the AEGEAN trial.3

“This [CHMP] recommendation highlights the potential of [durvalumab] to address an unmet need for patients with resectable lung cancer who need new treatment options that increase the time they live without recurrence or progression,” Susan Galbraigh, executive vice president, Oncology Haematology R&D, AstraZeneca, said in the news release.1 “AEGEAN underscores our commitment to transforming care in the early stages of lung cancer where there is the greatest potential for cure.”

AEGEAN Overview

The phase 3 study included patients at least 18 years of age with histologically or cytologically documented, newly diagnosed and previously untreated resectable stage IIA to IIIB (N2) NSCLC.4 Patients were required to have mediastinal lymph-node staging performed pathologically at the discretion of the investigator; to be candidates for planned surgical treatment with lobectomy, sleeve resection, or bilobectomy; have the presence of at least 1 lesion qualified as a target lesion per RECIST 1.1 criteria; and have an ECOG performance status of 0 or 1.

Patients in the study were randomly assigned 1:1 to be treated with either fixed-dose durvalumab at 1500 mg plus 4 cycles of platinum-based chemotherapy followed by surgery, or intravenous (IV) placebo every 3 weeks followed by surgery. Following the surgery, patients continued to be treated with durvalumab or IV placebo every 4 weeks for up to 12 cycles.

Of note, chemotherapy regimens were determined at the investigator’s discretion based on patients’ histologic findings. Surgery was prespecified to occur no more than 40 days after the administration of the last neoadjuvant treatment dose, and adjuvant treatment was scheduled as soon as clinically feasible within 10 weeks after surgery or within 3 weeks after the completion of postoperative radiotherapy, if indicated and according to local guidance, or if permitted, postoperative radiotherapy was required to begin within 8 weeks following surgery.

The primary end points included EFS and pCR rate; key secondary end points included major pathological response rate, disease-free survival, and OS.

Safety Data

Adverse effects (AEs) of any cause were reported in 96.5% vs 94.7% of patients in the durvalumab and placebo arms, respectively; AEs of any cause occurred in 91.0% vs 89.2% during the neoadjuvant treatment phase, respectively. Treatment-related AEs (TRAEs) occurred in 86.8% vs 80.7% of patients from the durvalumab and placebo arms, respectively. The incidence of grade 3/4 AEs of any cause was 42.4% vs 43.2% in the durvalumab and placebo arms, respectively. Patients experienced more occurrences of rashes and pruritus of any grade in the durvalumab arm vs the placebo arm, respectively (14.0% vs 8.5%; 11.7% vs 5.5%). Notably, grade 3/4 pruritus was uncommon and occurred with similar frequency in the 2 arms.

References

1. Recommendation based on AEGEAN phase III trial results which showed Imfinzi reduced the risk of recurrence, progression or death by 32% vs neoadjuvant chemotherapy alone. News Release. AstraZeneca. March 3, 2025. Accessed March 3, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/imfinzi-recommended-for-eu-approval-for-aegean.html
2. Heymach JV, Harpole D, Mitsudomi T, et al. Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N Engl J Med. 2023;389(18):1672-1684. doi:10.1056/NEJMoa2304875
3. FDA approves neoadjuvant/adjuvant duravlumab for resectable non–small cell lung cancer. FDA. August 15, 2024. Accessed March 3, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvantadjuvant-durvalumab-resectable-non-small-cell-lung-cancer
4. A study of neoadjuvant/adjuvant durvalumab for the treatment of patients with resectable non–small cell lung cancer (AEGEAN). ClinicalTrials.gov. Updated January 14, 2025. Accessed March 3, 2025. https://www.clinicaltrials.gov/study/NCT03800134