Phase 3 AEGEAN trial results show the benefit of perioperative immunotherapy‐based treatment for NSCLC

Phase 3 results from the AEGEAN trial show that patients with resectable non–small cell lung cancer (NSCLC) treated with perioperative durvalumab in addition to chemotherapy had significantly improved event-free survival (EFS) and rates of pathologic complete response (pCR) as compared to patients treated with chemotherapy alone.1 First presented at the 2023 American Association for Cancer Research meeting and published in The New England Journal of Medicine in early November, the study found that patients treated with perioperative durvalumab had a 32% lower chance of experiencing disease recurrence, progression events, or death as compared to patients treated with chemotherapy alone. At the first interim analysis of nearly 12 months, patients treated with perioperative durvalumab had a significantly longer EFS than those treated with chemotherapy alone. After stratification for disease stage (II or III) and programmed death ligand 1 expression (≥1% or <1%), the stratified hazard ratio of disease progression, recurrence, or death was 0.68 (95% CI, 0.53–0.88; p = .004). In addition, nearly four times as many patients treated with perioperative durvalumab achieved a pCR as compared to those treated with chemotherapy alone (17.2% vs. 4.3%, respectively). The results are based on 802 patients with resectable NSCLC (stage III–IIIB) randomized to platinum-based chemotherapy plus durvalumab before surgery followed by adjuvant durvalumab (n = 400) or platinum-based chemotherapy plus placebo before surgery followed by placebo (n = 402). For both groups, treatment before surgery was administered intravenously every 3 weeks for four cycles, and after surgery, it was administered intravenously every 4 weeks for 12 cycles. The results add to the growing body of evidence showing a benefit from adding immunotherapy to chemotherapy before and after surgical resection in patients with NSCLC. In October 2023, the US Food and Drug Administration approved perioperative pembrolizumab for the treatment of NSCLC based on the results of the phase 3 KEYNOTE-671 trial.2, 3 Commenting on the study, Daniel Morgensztern, MD, professor of medicine and chief director of thoracic oncology at the Washington University School of Medicine in St. Louis, Missouri, says that, if approved, the perioperative regimen evaluated in the AEGEAN trial “will represent another option for perioperative therapy in NSCLC.” He also underscores a key question left unanswered by both trials. “The main question about AEGEAN and KEYNOTE-671 is whether the patients need the adjuvant part, particularly those who achieve a complete pathologic response.” In an editorial published in October 2023 before the AEGEAN results and in response to the KEYNOTE-671 interim data, the authors laid out further questions that remain unanswered about the use of neoadjuvant and perioperative treatment for lung cancer, including whether there are patients for whom surgery can be omitted, what the optimal duration of therapy is, and what the optimal timing is for surgery after neoadjuvant immunotherapy.4 The authors wrote that the data coming from trials such as AEGEAN and KEYNOTE-671 (among others) will have a “profound impact on the practice of thoracic surgical oncology,” and they underscored that “it is paramount that thoracic surgeons remain engaged in both the standard-of-care and clinical trials settings as this paradigm evolves.”4