Neoadjuvant Nivolumab Plus Ipilimumab Versus Chemotherapy in Resectable Lung Cancer

Author(s): Mark M. Awad, MD, PhD¹; Patrick M. Forde, PhD, MBBCh²; Nicolas Girard, MD, PhD³; Jonathan Spicer, MD, PhD⁴; Changli Wang, MD⁵; Shun Lu, MD, PhD⁶; Tetsuya Mitsudomi, MD⁷; Enriqueta Felip, MD, PhD⁸; Stephen R. Broderick, MD²; Scott J. Swanson, MD⁹; Julie Brahmer, MD²; Keith Kerr, MBChB¹⁰; Gene B. Saylors, MD¹¹; Ke-Neng Chen, MD, PhD¹²; Vishwanath Gharpure, MD¹³; Jaclyn Neely, PhD¹³; David Balli, PhD¹³; Nan Hu, PhD¹³; Mariano Provencio Pulla, MD, PhD¹⁴

Source: https://doi.org/10.1200/JCO-24-0223

Dr. Maen Hussein's Thoughts

Results showed the median event-free survival (EFS) was 54.8 months with nivolumab plus ipilimumab vs 20.9 months with chemotherapy. Three-year EFS rates were 56% vs 44%. Three-year overall survival (OS) rates were 73% vs 61% pathologic complete response rates were 20.4% vs 4.6%. This was three cycles of nivolumab and one dose of ipilimumab vs chemotherapy.

PURPOSE

Neoadjuvant immune checkpoint blockade with nivolumab plus ipilimumab improves overall survival (OS) in non–small cell lung cancer (NSCLC); however, randomized data for resectable lung cancer are limited. We report results from the exploratory concurrently randomized nivolumab plus ipilimumab and chemotherapy arms of the international phase III CheckMate 816 trial.

METHODS

Adults with stage IB-IIIA (American Joint Committee on Cancer seventh edition) resectable NSCLC received three cycles of nivolumab once every 2 weeks plus one cycle of ipilimumab or three cycles of chemotherapy (on day 1 or days 1 and 8 of each 3-week cycle) followed by surgery. Analyses included event-free survival (EFS), OS, pathologic response, surgical outcomes, biomarker analyses, and safety.

RESULTS

A total of 221 patients were concurrently randomly assigned to nivolumab plus ipilimumab (n = 113) or chemotherapy (n = 108). At a median follow-up of 49.2 months, the median EFS was 54.8 months (95% CI, 24.4 to not reached [NR]) with nivolumab plus ipilimumab versus 20.9 months (95% CI, 14.2 to NR) with chemotherapy (HR, 0.77 [95% CI, 0.51 to 1.15]); 3-year EFS rates were 56% versus 44%. Higher rates of EFS events were initially seen, with later benefit favoring nivolumab plus ipilimumab; 3-year OS rates were 73% versus 61% (HR, 0.73 [95% CI, 0.47 to 1.14]); pathologic complete response rates were 20.4% versus 4.6%, respectively. In the respective arms, 83 (74%) and 82 patients (76%) underwent definitive surgery. Grade 3-4 treatment-related adverse events occurred in 14% and 36% of patients, respectively.

CONCLUSION

Neoadjuvant nivolumab plus ipilimumab showed potential long-term clinical benefit versus chemotherapy, despite early crossing of EFS curves in the preoperative phase and a lower rate of high-grade toxicity.

Author Affiliations

¹Dana-Farber Cancer Institute, Boston, MA;²The Bloomberg–Kimmel Institute for Cancer Immunotherapy, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, MD;³Institut du Thorax Curie-Montsouris, Institut Curie, Paris, France;⁴McGill University Health Centre, Montreal, QC, Canada;⁵Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China;⁶Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China;⁷Kindai University Faculty of Medicine, Osaka-Sayama, Japan;⁸Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Universitat Autònoma Barcelona, Barcelona, Spain;⁹Brigham and Women’s Hospital, Boston, MA;¹⁰Aberdeen Royal Infirmary, Aberdeen, United Kingdom;¹¹Charleston Oncology, Charleston, SC;¹²Peking University School of Oncology, Beijing Cancer Hospital, Beijing, China;¹³Bristol Myers Squibb, Princeton, NJ;¹⁴Hospital Universitario Puerta de Hierro, Madrid, Spain

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Phase III Study of Mediastinal Lymph Node Dissection for Ground Glass Opacity–Dominant Lung Adenocarcinoma

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