Perioperative Durvalumab Plus Chemotherapy Plus New Agents for Resectable Non-Small-Cell Lung Cancer: The Platform Phase 2 NeoCOAST-2 Trial

The NeoCOAST-2 trial, published in Nature Medicine, evaluates the efficacy and safety of neoadjuvant durvalumab-based combination regimens for resectable stage IIA–IIIB non-small cell lung cancer (NSCLC). This phase II, open-label, multicenter study randomized patients to receive durvalumab either alone or in combination with novel immune modulators, including oleclumab (anti-CD73) or monalizumab (anti-NKG2A), alongside platinum-based chemotherapy prior to surgery. The results demonstrated higher major pathological response (MPR) and pathological complete response (pCR) rates with durvalumab combinations compared to durvalumab plus chemotherapy alone, without compromising surgical feasibility or safety. Most patients proceeded to complete resection, with acceptable perioperative complication rates and no new safety signals. 
 
For CTSNet’s global cardiothoracic surgery audience, this study is particularly relevant as it demonstrates how immunomodulatory combinations can enhance tumor clearance preoperatively while maintaining operability and safety. These findings highlight the evolving role of surgery within multimodal immunotherapy protocols, shaping future standards for curative-intent management of resectable NSCLC.