ORLANDO, Fla. ― Pre-surgical immunotherapy and chemotherapy regimens followed by post-surgical immunotherapy significantly improved event-free survival (EFS) and pathological complete response (pCR) rates compared to chemotherapy alone for patients with operable non-small cell lung cancer ( NSCLC), according to Phase III trial results presented today by researchers from The University of Texas MD Anderson Cancer Center at the American Association for Cancer Research (AACR) Annual Meeting 2023.
The AEGEAN trial evaluated durvalumab given perioperatively, meaning that it was administered before and after surgery. Trial participants received preoperative durvalumab (neoadjuvant) and platinum-based chemotherapy followed by postoperative (adjuvant) durvalumab or neoadjuvant placebo and chemotherapy followed by adjuvant placebo.
This represents the first data presented on the benefit of perioperative immunotherapy for operable NSCLC and adds to the evidence supporting the benefits of both neoadjuvant and adjuvant immunotherapy for these patients.
“Our goal is to improve lung cancer cure. Over decades of research with adjuvant and neoadjuvant chemotherapy, we’ve only managed to increase cure by about 5%,” said principal investigator John Heymach, MD, Ph.D., chair of Thoracic/Head & Neck Medical Oncology at MD Anderson. “This one study alone has the potential to increase that percentage significantly, and we look forward to more improvements in the future.”
Of the patients who received durvalumab perioperatively, 17.2% had a pCR compared with only 4.3% of those who received chemotherapy alone. In the first EFS interim analysis, with a median follow-up of 11.7 months, the median EFS was 25.9 months in the placebo arm, but was not achieved in the durvalumab arm.
These data correspond to a 32% lower likelihood of patients experiencing disease recurrence, developmental events or death with immunotherapy-based treatment when compared with chemotherapy alone. Approximately four times as many patients treated with durvalumab plus chemotherapy achieved a pCR when compared to those treated with chemotherapy alone.
Durvalumab, an immune checkpoint inhibitor that targets PD-L1, has previously been approved to treat certain patients with bile duct cancer, liver cancer, small cell lung cancer and NSCLC. Currently, durvalumab is used to treat patients with locally inoperable NSCLC after definitive chemoradiotherapy and for patients with metastatic NSCLC in combination with tremelimumab and platinum-based chemotherapy.
For resectable NSCLC, previous studies have shown some benefit from using adjuvant or neoadjuvant immunotherapy, but Heymach says the benefits so far have been modest. MD Anderson is involved in a long-term, multidisciplinary effort to use neoadjuvant treatments to improve patient outcomes. A number of clinical studies, such as the NEOSTAR and NeoCOAST trials, are evaluating new neoadjuvant and combination immunotherapy for removing viable tumors preoperatively and for reducing recurrence rates.
The AEGEAN Phase III trial was a randomized, double-blind, placebo-controlled study to evaluate the perioperative benefit of durvalumab added to platinum-based chemotherapy in untreated adults with stage IIA-IIIB NSCLC. A total of 802 patients were randomized 1:1 to each group. The main end points of this study were pCR, which was assessed by a central laboratory, and EFS using a blind independent central review.
Patients with EGFR/ALK mutations were excluded from the modified intention-to-treat population. A total of 740 patients were included in the efficacy analysis, including 366 in the durvalumab group and 374 in the placebo group. The mean age of participants in each group was 65 years and 71.6% were male. Patients 53.6% were white, 41.5% Asian and 4.9% other.
Overall, the treatment was well tolerated and side effects were consistent with previous studies. The investigators observed a maximum rate of 3–4 for each cause of adverse events in 42.3% and 43.4% of patients in the durvalumab and placebo groups, respectively.
Benefits on pCR and EFS were largely consistent across predefined patient subgroups, and trials continue to assess long-term EFS and disease-free survival and overall survival outcomes.
“This study shows that the combination of neoadjuvant and adjuvant durvalumab offers benefits to patients and may have the potential to change the standard of care for patients with operable non-small cell lung cancer,” said Heymach. “Going forward, we face a series of questions about how to build more effective regimens without giving more treatment than is necessary.”
Heymach explained that future studies should determine which patients benefit most from neoadjuvant therapy and may be able to avoid further treatment as well as those who remain at high risk of relapse and may require a more intensive adjuvant regimen.
This study was conducted by AstraZeneca. Heymach serves on the advisory committee for Genentech, Mirati Therapeutics, Eli Lilly & Co, Janssen Pharmaceuticals, Boehringer Ingelheim, Regeneron, Takeda, BerGenBio, Jazz Pharmaceuticals, Curio Science, Novartis, AstraZeneca, BioAtla, Sanofi, Spectrum Pharmaceuticals, GSK, EMD Serono, Chugai Blueprint Drugs and Pharmaceuticals. He receives research support from AstraZeneca, Boehringer Ingelheim, Spectrum, Mirati Therapeutics, Bristol Myers Squibb and Takeda, as well as royalty and licensing fees from Spectrum. A full list of collaborating authors and their disclosures can be found here.
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