FDA Approves Perioperative Durvalumab Plus Chemotherapy in Resectable NSCLC

The FDA has approved durvalumab (Imfinzi) in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by single-agent durvalumab as adjuvant treatment after surgery, for adult patients with resectable (tumors ≥4 cm and/or node positive) non–small cell lung cancer and no known EGFR mutations or ALK rearrangements.¹

The approval was based on data from the phase 3 AEGEAN trial (NCT03800134), which demonstrated a statistically significant and clinically meaningful reduction in the risk of recurrence, progression, or death with the chemoimmunotherapy regimen vs chemotherapy alone. The median event-free survival (EFS) was not reached (NR; 95% CI, 31.9-NR) with durvalumab vs 25.9 months (95% CI, 18.9-NR) with placebo (stratified HR, 0.68; 95% CI, 0.53-0.88; P = .004). The 12- and 24-month EFS rates with durvalumab were 73.4% (95% CI, 67.9%-78.1%) and 63.3% (95% CI, 56.1%-69.6%), respectively, vs 64.5% (95% CI, 58.8%-69.6%) and 52.4% (95% CI, 45.4%-59.0%) with placebo.^2,3

In a final analysis of pathologic complete response (pCR), results indicated that the pCR rate with durvalumab (n = 366) was 17.2% (95% CI, 13.5%-21.5%) vs 4.3% (95% CI, 2.5%-6.9%) with placebo (n = 374), reflecting an absolute difference of 12.9% (95% CI, 8.7%-17.6%; P < .001). The major pathologic response (MPR) rates with durvalumab and placebo were 33.3% and 12.3%, respectively, reflecting an absolute difference of 21.0% (95% CI, 15.1%-26.9%; P < .001).

The global, double-blind, placebo-controlled AEGEAN trial enrolled patients with treatment-naive, resectable stage IIA to IIIB (N2) NSCLC per American Joint Committee on Cancer (AJCC) 8th edition criteria with plans to undergo lobectomy, sleeve resection, or bilobectomy. In addition to an ECOG performance status of 0 or 1, patients had to have confirmed PD-L1 status and no documented EGFR or ALK aberrations.

Between January 2, 2019, and April 19, 2022, 802 patients were randomly assigned 1:1 to neoadjuvant therapy consisting of 1500 mg of intravenous (IV) durvalumab plus platinum-based chemotherapy every 3 weeks for 4 cycles, or IV placebo plus platinum-based chemotherapy on the same schedule. After surgery, patients received an additional 12 cycles of durvalumab or placebo every 4 weeks, depending on randomization. Post-operative radiotherapy was permitted in accordance with local guidance.

Primary end points were pCR by central laboratory per IASLC 2020 criteria and EFS using blinded independent central review (BICR) per RECIST v1.1 criteria. Secondary end points included MPR by central laboratory per IASLC 2020 criteria, disease-free survival (DFS) using BICR per RECIST v1.1 criteria, and overall survival (OS).

References

1. FDA approves neoadjuvant/adjuvant durvalumab for resectable non-small cell lung cancer. FDA. August 15, 2024. Accessed August 15, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvantadjuvant-durvalumab-resectable-non-small-cell-lung-cancer
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 advisory committee reviewed Imfinzi for treatment of resectable non-small cell lung cancer based on AEGEAN phase III trial results. News release. AstraZeneca. July 25, 2024. Accessed August 12, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/odac-reviewed-imfinzi-in-resectable-lung-cancer.html