Neoadjuvant Nivolumab (NIVO) + Chemotherapy (Chemo) versus Chemo for Resectable Non–Small Cell Lung Cancer (NSCLC): Event-free Survival (EFS) by Surgical Outcomes from CheckMate 816

Objective: Neoadjuvant NIVO in combination with platinum-doublet chemo previously demonstrated statistically significant and clinically meaningful improvement in pathologic complete response (pCR) and EFS vs chemo alone, without an increase in post-surgical complications, in patients with resectable NSCLC in the phase 3 CheckMate 816 study (NCT02998528). Surgical outcomes, including safety, have been reported previously. Here, we report additional surgical outcomes analyses from CheckMate 816.

Methods: Patients with newly diagnosed, resectable, stage IB (≥ 4 cm) to IIIA NSCLC (AJCC 7th edition), an Eastern Cooperative Oncology Group performance status of 0-1, and no known sensitizing EGFR mutations or ALK alterations were included. Patients were randomized 1:1 to receive neoadjuvant NIVO 360 mg every 3 weeks (Q3W) plus platinum-doublet chemo Q3W (3 cycles) or chemo Q3W (3 cycles); patients then had surgery ≤ 6 weeks post-treatment. Primary endpoints were EFS (time from randomization to any disease progression precluding surgery; disease progression or recurrence after surgery; or death) and pCR (0% residual viable tumor in the primary tumor and lymph nodes based on immune-related pathological response criteria), both assessed by blinded independent review. In these post-hoc exploratory analyses, EFS was evaluated in patient subgroups by surgical approach (minimally invasive, thoracotomy, or conversion from minimally invasive to open surgery), by type of surgery (lobectomy or pneumonectomy), and by completeness of resection (R0 or R1).

Results: At database lock (October 20, 2021), median follow-up was 29.5 months. Of the 358 patients randomized to NIVO + chemo (n = 179) or chemo (n = 179), 149/179 (83%) and
135/179 (75%), respectively, received definitive surgery. Overall, EFS improvement was seen with NIVO + chemo vs chemo alone (Table), regardless of surgical approach (hazard ratio [HR]: 0.46 and 0.67 for minimally invasive surgery and thoracotomy, respectively), type of surgery (HR: 0.58 for lobectomy; not calculated for pneumonectomy), or completeness of resection (HR: 0.59 with R0 resection; not calculated with R1 resection); sample size and number of EFS events were limited in some subgroups. Notably, in the NIVO + chemo arm, median EFS was not reached in most patient subgroups by surgical approach, type of surgery, or completeness of resection. In the NIVO + chemo arm, 2-year EFS rates (95% CI) were: 81% (66-90) and 69% (58-78) in patients who underwent minimally invasive surgery or thoracotomy, respectively; 70% (60-78) and 76% (52-90) in those who had lobectomy or pneumonectomy, respectively; and 72% (62-79) in patients who had R0 resection.

Conclusions: In CheckMate 816, the addition of NIVO to neoadjuvant chemo did not impede surgical feasibility. EFS benefit was observed in patients treated with NIVO + chemo vs chemo, regardless of surgical approach, type of surgery, or completeness of resection. These results further support neoadjuvant NIVO + chemo as a treatment option for patients with resectable NSCLC.

Stephen Broderick (1), Changli Wang (2), Fumihiro Tanaka (3), Ke-Neng Chen (4), Hiroyuki Ito (5), Moishe Liberman (6), Qixun Chen (7), Nicolas Girard (8), Shun Lu (9), Mariano Provencio (10), Tetsuya Mitsudomi (11), Mark M. Awad (12), Enriqueta Felip (13), Scott Swanson (12), Patrick M. Forde (1), Junliang Cai (14), Javed Mahmood (14), Nan Hu (14), Phuong Tran (14), Jonathan Spicer (15), (1) Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA, (2) Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China, (3) University of Occupational and Environmental Health, Kitakyushu, Japan, (4) Peking University School of Oncology, Beijing Cancer Hospital, Beijing, China, (5) Kanagawa Cancer Center, Yokohama, Japan, (6) Centre hospitalier de l'Université de Montréal, Montreal, Québec, Canada, (7) Zhejiang Cancer Hospital, Hangzhou, China, (8) Institut du Thorax Curie-Montsouris, Institut Curie, Paris, France, (9) Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai, China, (10) Hospital Universitario Puerta de Hierro, Madrid, Spain, (11) Kindai University Hospital, Osaka, Japan, (12) Dana-Farber Cancer Institute, Boston, MA, USA, (13) Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain, (14) Bristol Myers Squibb, Princeton, NJ, USA, (15) McGill University Health Center, Montreal, Québec, Canada

Thomas D'Amico

Invited Discussant

Dr. Thomas A. D’Amico is a graduate of Harvard University (BA) and the College of Physicians & Surgeons of Columbia University (MD). He received training in General Surgery and Thoracic Surgery at Duke University Medical Center. After completing a Fellowship in Thoracic Surgical Oncology at the Memorial Sloan-Kettering Cancer Center, Dr. D’Amico joined the faculty at Duke University Medical Center in 1996. He is currently the Gary Hock Endowed Professor, Chief of General Thoracic Surgery, and Director of the Thoracic Oncology Program of the Duke Cancer Institute

Dr. D’Amico is in leadership positions in the American Association for Thoracic Surgery, including the Board of Directors, the Membership Committee, and the Ethics Committee. He is an Associate Editor for the Journal of Thoracic and Cardiovascular Surgery and serves on the editorial board of the Annals of Surgery and the Journal of the American College of Surgeons. Finally, he is the active in the NCCN, as a member of NCCN Board of Directors and Guidelines Steering Committee, the Chair of the Quality and Outcomes Committee, as well as a member of the Non-Small Cell Lung Cancer and Small Cell Lung Cancer Guidelines Committees and co-chair of the Esophageal Cancer Guidelines Committee.

Stephen Broderick

Abstract Presenter

Dr. Stephen R. Broderick MD, MPHS is a thoracic surgeon at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Centerand Sibley Memorial Hospital.  After graduation from the Georgetown University School of Medicine he completed a residency in general surgery at the Weill Cornell New York Presbyterian Hospital.  During residency he dedicated two years to thoracic oncology research at Memorial Sloan Kettering Cancer Center.  His work at MSKCC focused on DNA copy number and gene expression changes in lung adenocarcinoma and was included in The Cancer Genome Atlas.  Following residency he completed a fellowship in cardiothoracic surgery at Washington University in St. Louis.  Dr Broderick’s academic interests include thoracic surgery clinical outcomes and perioperative applications of systemic therapy for NSCLC.  His clinical interests include thoracic surgical oncology as well as the breadth of benign conditions of the chest and foregut.

Specialties: General Thoracic, Thoracic, Lung, Procedures, Anatomy and Conditions, Lung--Cancer, Lung--Other, Treatment/Procedure/Operation/Surgery, Lung, Lung--Cancer, Lung--Other, Minimally Invasive, Robotics