Dr Bhora on How Perioperative Immunotherapy Is Reshaping the Treatment Paradigm in Resectable NSCLC

“In the last 3 to 4 years, [these trials] have not just moved the needle, but [have] truly been transformational; [they] flip the paradigm on its head. The key to all of this is recognition of…the fact that a pathological complete response really does translate into significantly improved long-term survival and event-free survival.”

Faiz Y. Bhora, MD, FACS, professor of surgery at the Hackensack Meridian School of Medicine and Regional Chair of Surgery/Chief of Thoracic Surgery for Hackensack Meridian Health’s Central Region, discussed how data from recent phase 3 neoadjuvant and perioperative immunotherapy trials—including CheckMate 816 (NCT02998528), KEYNOTE-091 (NCT03425643), and AEGEAN (NCT03800134)—have reshaped the treatment paradigm for patients with resectable non–small cell lung cancer (NSCLC).

CheckMate 816 evaluated neoadjuvant nivolumab in combination with platinum-based chemotherapy in patients with resectable stage IB to IIIA NSCLC. The trial demonstrated a significant improvement in pathological complete response (pCR) and event-free survival (EFS) with chemoimmunotherapy compared with chemotherapy alone, establishing pCR as a clinically meaningful surrogate for long-term outcomes. AEGEAN assessed perioperative durvalumab plus chemotherapy, showing an improvement in EFS vs placebo plus chemotherapy and supporting the integration of immunotherapy to perioperative approaches. KEYNOTE-091 examined adjuvant pembrolizumab after complete resection with or without adjuvant chemotherapy and demonstrated a disease-free survival benefit in patients with stage IB to IIIA disease.

Based on these results, perioperative immunotherapy strategies have rapidly expanded, Bhora said. He emphasized that the consistent association between pCR and improved long-term survival across these trials underscores the importance of achieving deep pathological responses. These findings also highlight the need to refine patient selection for neoadjuvant versus adjuvant immunotherapy, he noted.

This evidence may have “flipped the paradigm,” but the success of these approaches depends on systematic biomarker evaluation, Bhora noted. Early molecular testing for EGFR, ALK, and PD-L1 status remains crucial for appropriately guiding treatment decision-making, as patients with targetable genomic alterations derive greater benefit from targeted agents vs immunotherapy.

Additionally, although each component of the perioperative regimen contributes to the observed outcomes, it remains challenging to isolate the specific impact of individual agents, paralleling challenges seen in other multimodality treatment strategies, Bhora concluded.