Perioperative Durvalumab-Based Regimen Receives European Approval for Resectable NSCLC

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The European Commission has granted approval to durvalumab (Imfinzi) for use as neoadjuvant therapy in combination with chemotherapy and as adjuvant monotherapy for the treatment of patients with resectable non–small cell lung cancer (NSCLC) at high risk of recurrence and without EGFR mutations or ALK rearrangements.1

The approval in the European Union comes just one month after the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended the regimen for approval.2 Both decisions were based on data from the phase 3 AEGEAN trial (NCT03800134),1,2 which showed a statistically significant and clinically meaningful improvement in event-free survival (EFS) with the durvalumab-based regimen vs chemotherapy alone (HR, 0.68; 95% CI, 0.53-0.88; P =.003902).1,3 Additionally, the pathologic complete response (pCR) rate was 17.2% with the neoadjuvant chemoimmunotherapy regimen vs 4.3% with neoadjuvant chemotherapy alone (pCR difference, 13.0%; 95% CI, 8.7%-17.6%).3

The regimen was also well tolerated, and no new safety signals were seen in either the neoadjuvant or adjuvant settings.1 The addition of durvalumab to chemotherapy in the neoadjuvant setting also reflected a safety profile that was similar to its known profile and did not affect patients’ ability to undergo surgery vs chemotherapy alone.

“Today’s approval provides an important new treatment option that should become a backbone combination approach for patients in Europe with resectable NSCLC, who have historically faced high rates of recurrence and a poor prognosis. When added to neoadjuvant chemotherapy, perioperative durvalumab meaningfully improved outcomes in this curative-intent setting, significantly extending the time patients lived without their cancer returning,” Martin Reck, MD, PhD, head of the Department of Thoracic Oncology at the Lung Clinic Grosshansdorf in Germany, and member of the AEGEAN Steering Committee and investigator in the trial, stated in a news release.

AEGEAN was a randomized, double-blind, global, multi-center, placebo-controlled phase 3 trial comparing perioperative treatment with durvalumab in patients with resectable stage IIA to IIIB NSCLC, irrespective of PD-L1 expression.

A total of 802 patients were randomly assigned to receive a 1500-mg fixed dose of durvalumab plus chemotherapy or placebo plus chemotherapy every 3 weeks for 4 cycles before surgery, followed by durvalumab or placebo every fo4ur weeks for up to 12 cycles after surgery.

The primary end points were pCR rate, which was defined as no viable tumor in the resection specimen and lymph nodes following neoadjuvant therapy, and EFS, which was defined as the time from randomization to an event like tumor recurrence, progression precluding definitive surgery, or death. Key secondary end points were major pathologic response rate, defined as residual viable tumor of less than or equal to 10% in the resected primary tumor following neoadjuvant therapy, disease-free survival, overall survival (OS), safety, and quality of life.

With respect to OS, interim results were presented at the 2024 IASLC World Conference on Lung Cancer with 35% data maturity. The findings showed a favorable trend with the durvalumab-based perioperative regimen with a median OS that had not been reached vs 53.2 months with chemotherapy alone (HR, 0.89; 95% CI, 0.70-1.14). Notably, the OS data had not been tested for statistical significance at this interim analysis and will continue to be assessed as a key secondary end point at the final analysis.

“Today’s approval marks an important step towards improving outcomes for patients in Europe with resectable NSCLC, enabling more patients to access this important immunotherapy-based regimen. This new indication builds on the established role of [durvalumab] in unresectable disease and underscores our commitment to transforming care in the early stages of lung cancer where there is the greatest potential for cure,” Dave Fredrickson, executive vice president, Oncology Haematology Business Unit, AstraZeneca, said.

The regimen is also approved in the United States,4 China, and several other countries in this setting based on data from AEGEAN, with pending regulatory decisions in Japan and additional countries.1

References

1. Imfinzi-based perioperative regimen approved in the EU for resectable non-small cell lung cancer. News release. AstraZeneca. April 4, 2025. Accessed April 4, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/imfinzi-approved-in-eu-for-aegean.html
2. Imfinzi-based perioperative regimen recommended for approval in the EU by CHMP for resectable non-small cell lung cancer. News release. AstraZeneca. March 3, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/imfinzi-recommended-for-eu-approval-for-aegean.html
3. 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
4. FDA approves neoadjuvant/adjuvant durvalumab for resectable non-small cell lung cancer. FDA. August 15, 2024. Accessed April 4, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvantadjuvant-durvalumab-resectable-non-small-cell-lung-cancer