Combination immunotherapy with the anti–PD-L1 monoclonal antibody durvalumab and other novel agents seemed to outperform durvalumab alone in the neoadjuvant setting for early-stage non–small cell lung cancer (NSCLC), according to researchers from The University of Texas MD Anderson Cancer Center, Houston. The findings, published in Cancer Discovery,1 were first presented at the 2022 American Association for Cancer Research Annual Meeting.
Tina Cascone, MD, PhD
The multicenter, randomized phase II NeoCOAST clinical trial evaluated neoadjuvant durvalumab alone and in combination with each of the following novel immunotherapies: the anti-CD73 monoclonal antibody oleclumab, the anti-NKG2A monoclonal antibody monalizumab, and the anti-STAT3 antisense oligonucleotide danvatirsen. Although the study was not statistically powered to compare arms, all combinations resulted in numerically higher major pathologic response rates than with durvalumab monotherapy.
“This study builds on the growing evidence that combination immunotherapy has a role in the neoadjuvant setting for this patient population,” said Tina Cascone, MD, PhD, Assistant Professor of Thoracic/Head and Neck Medical Oncology and lead author of the study. “Ultimately, we want to give patients a chance to live longer without their cancer returning.”
Key Findings
The NeoCOAST study enrolled 84 patients with untreated, resectable (> 2 cm), stage I–IIIA NSCLC between March 2019 and September 2020. The primary endpoint was investigator-assessed major pathologic response, defined as ≤ 10% residual viable tumor cells in the resected tumor tissue and sampled nodes at surgery. The investigators assessed pathologic complete response as a secondary endpoint. All combinations had numerically higher rates of major pathologic response and pathologic complete response than monotherapy, and there were no statistically significant differences in responses between the combination arms:
For the patients who received durvalumab monotherapy, major pathologic response occurred in 11.1% and pathologic complete response, in 3.7%, which is comparable to results from other monotherapy studies.
Major pathologic response rates for combination therapy ranged from 19% (with oleclumab) to 31.3% (with danvatirsen), and pathologic complete response rates ranged from 9.5% (with oleclumab) to 12.5% (with danvatirsen). For combination therapy with monalizumab, major pathologic response was 30%, and pathologic complete response was 10%.
The safety profile in the durvalumab monotherapy arm (treatment-related adverse events in 34.6% of patients) was similar to previously published data for anti–PD-1/PD-L1 antibodies. No new safety signals were identified with any of the combination regimens (treatment-related adverse events seen in 43.8%–57.1% of patients).
Based on these results and the recent approval of neoadjuvant nivolumab plus chemotherapy, the team has launched a follow-up randomized clinical trial, NeoCOAST-2, with Dr. Cascone serving as the global principal investigator. The trial is now enrolling patients with resectable, stage IIA–IIIA NSCLC to receive neoadjuvant durvalumab combined with chemotherapy and either oleclumab or monalizumab, followed by surgery and adjuvant durvalumab plus oleclumab or monalizumab.
DISCLOSURE: Dr. Cascone has received personal fees and other institutional support from MedImmune/AstraZeneca, as well as grants, personal fees, and other support from Bristol Myers Squibb, Regeneron, Merck & Co, Pfizer, Genentech, Arrowhead Pharmaceuticals, Roche, Medscape, OncLive, PeerView, Clinical Care Options, The Mark Foundation for Cancer Research, Physicians’ Education Resource, IDEOlogy Health, the Parker Institute for Cancer Immunotherapy, the Society for Immunotherapy of Cancer, the International Association for the Study of Lung Cancer, Dava Oncology, and EMD Serono. For full disclosures of the study authors, visit aacrjournals.org.
REFERENCE
1. Cascone T, Kar G, Spicer JD, et al: Neoadjuvant durvalumab alone or combined with novel immuno-oncology agents in resectable lung cancer: The phase 2 NeoCOAST platform trial. Cancer Discov 13:2394-2411, 2023.
