Adding perioperative durvalumab to neoadjuvant chemotherapy can improve outcomes in patients with resectable non-small cell lung cancer (NSCLC), according to research presented at the AACR Annual Meeting 2023.
In the phase 3 AEGEAN trial, perioperative durvalumab improved the pathologic complete response (pCR) rate and prolonged event-free survival (EFS) in patients with resectable NSCLC.
“AEGEAN is the first phase 3 study to describe the benefit of perioperative immunotherapy plus neoadjuvant chemotherapy,” said study presenter John V. Heymach, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston.
“Perioperative durvalumab plus neoadjuvant chemotherapy is a potential new treatment for patients with resectable NSCLC,” he added.
Trial and Treatment Details
The AEGEAN trial (ClinicalTrials.gov Identifier: NCT03800134) included 802 patients with treatment-naive, stage IIA-IIIB, resectable NSCLC. Patients were randomly assigned to receive durvalumab or placebo, each in combination with neoadjuvant chemotherapy.
All patients received 4 cycles of chemotherapy, which consisted of cisplatin/carboplatin plus pemetrexed for patients with non-squamous NSCLC. Patients with squamous NSCLC received carboplatin plus paclitaxel or cisplatin/carboplatin plus gemcitabine. Patients in the durvalumab arm received 1500 mg of the drug every 3 weeks for 4 cycles, and patients in the control arm received placebo. After surgery, patients in the durvalumab arm received the drug again, at 1500 mg every 4 weeks for up to 12 cycles.
The efficacy analysis included 366 patients in the durvalumab arm and 374 in the placebo arm. Baseline characteristics were generally well balanced between the arms. Most patients in the durvalumab and placebo arms completed 4 cycles of chemotherapy (84.7% and 87.2%, respectively) and 4 cycles of either durvalumab or placebo (86.9% and 88.5%, respectively).
Most patients went on to surgery — 80.6% in the durvalumab arm and 80.7% in the placebo arm. The R0 resection rate was 94.7% and 91.3%, respectively. Twenty-four percent of patients in the durvalumab arm completed adjuvant durvalumab, and 23.2% were still receiving it at last follow-up.
Efficacy and Safety Results
The median follow-up was 11.7 months. The median EFS was not reached in the durvalumab arm and was 25.9 months in the placebo arm (hazard ratio, 0.68; 95% CI, 0.53-0.88; P =.004).
The 12-month EFS rate was 73.4% with durvalumab and 64.5% with placebo. The 24-month EFS rate was 63.3% and 52.4%, respectively.
In the final pCR analysis, 17.2% of patients achieved a pCR in the durvalumab arm, as did 4.3% of patients in the placebo arm (P =.000036). The major pathologic response rate was 33.3% with durvalumab and 12.3% with placebo (P =.000002).
The safety analysis included 400 patients in the durvalumab arm and 399 in the placebo arm. The rate of grade 3-4 adverse events considered possibly related to treatment was 32.3% in the durvalumab arm and 33.1% in the placebo arm. Grade 3-4 immune-mediated adverse events occurred in 4.0% and 2.5% of patients, respectively.
Dr Heymach said this study is ongoing, and disease-free survival and overall survival will be assessed.
Disclosures: This research was supported by AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Heymach JV, Harpole D, Mitsudomi T, et al. AEGEAN: A phase 3 trial of neoadjuvant durvalumab + chemotherapy followed by adjuvant durvalumab in patients with resectable NSCLC. AACR 2023. April 14-19, 2023. Abstract CT005.