A landmark phase 3 clinical trial has demonstrated that adding the PD-1 inhibitor nivolumab to standard chemotherapy before surgery significantly improves long-term survival in patients with resectable non-small cell lung cancer (NSCLC). The CheckMate 816 trial results, published in the New England Journal of Medicine and presented at the American Society of Clinical Oncology Annual Meeting, show patients receiving the combination therapy were approximately 10% more likely to be alive at 5 years compared to those receiving chemotherapy alone.
Trial Design and Patient Population
The CheckMate 816 trial, led by Prof. Patrick Forde of Trinity St. James's Cancer Institute, enrolled 358 patients globally diagnosed with NSCLC at a stage amenable to surgical resection. The study addressed a critical unmet need, as despite surgical intervention, more than 50% of patients with stage 2 or 3 lung cancer eventually experience disease relapse.
The trial compared neoadjuvant nivolumab plus chemotherapy against chemotherapy alone in patients with resectable NSCLC, representing the first study to demonstrate long-term survival benefit from immunotherapy in helping to cure earlier-stage lung cancer.
Pathologic Response and Survival Outcomes
The most striking finding emerged among patients achieving pathologic complete response (pCR), defined as no viable cancer remaining at the time of surgery. Among the 24% of patients treated with immunotherapy plus chemotherapy who achieved pCR, no patient had died from lung cancer by 5 years, suggesting potential for cure in this subset.
Earlier reports from the CheckMate 816 trial had already shown that patients receiving the combination therapy were more likely to have their cancer eliminated completely by surgery and experienced lower rates of cancer relapse. Importantly, side effects were not increased with the addition of immunotherapy, and surgical procedures generally proceeded without complications.
Regulatory Impact and Clinical Implementation
These findings have translated into regulatory approvals across multiple countries, with neoadjuvant nivolumab plus chemotherapy now established as standard treatment for eligible patients globally, including in Ireland. The approval represents a significant advancement in the treatment paradigm for resectable NSCLC.
Future Directions and Combination Strategies
Prof. Forde is co-leading the international NeoCOAST-2 trial, with sites in Ireland at TSJCI, Beaumont, Galway and Mater Hospitals. Results from this study, published in Nature Medicine, demonstrate that patients receiving standard chemo-immunotherapy plus an antibody drug conjugate (ADC) before surgery were more likely to have no viable cancer remaining at surgery, suggesting potential for further outcome improvements.
"Immunotherapy has helped many patients with stage 4 lung cancer live longer with good quality of life. Until recently we have not had new treatments available that can increase the chances of cure after lung cancer surgery," Prof. Forde stated. "The use of immunotherapy with chemotherapy before lung cancer surgery has now been shown to reduce the risk of cancer coming back and improve long term survival."
Historical Context and Research Evolution
Prof. Forde's research trajectory in neoadjuvant immunotherapy began during his tenure at Johns Hopkins University, where he led the first clinical trial of immunotherapy prior to surgery for lung cancer, published in the New England Journal of Medicine in 2018. That pioneering study of 20 patients showed that almost half had little or no remaining cancer after receiving 2 doses of immunotherapy before surgery.
In 2024, Prof. Forde joined Trinity St. James's Cancer Institute as the Patrick Prendergast Professor of Clinical Immuno-Oncology, a position established through philanthropic support from Dr. Stanley Quek. His current focus involves expanding access to cutting-edge cancer clinical trials across Ireland, continuing the advancement of immunotherapy strategies in earlier-stage disease settings.
