Journal Article

Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial

Fujimoto, Junya, Roth, Jack A, Weissferdt, Annikka, Allison, James P, Antonoff, Mara B, Jenq, Robert R, Mehran, Reza J, Skoulidis, Ferdinandos, Bernatchez, Chantale, Carter, Brett W, Altan, Mehmet, Francisco-Cruz, Alejandro, Wargo, Jennifer A, Fossella, Frank V, Rice, David C, Byers, Lauren Averett, Swisher, Stephen G, William, Jr, William N, Wistuba, Ignacio I, Dejima, Hitoshi, Kurie, Jonathan M, Heymach, John V, Elamin, Yasir Y, Tran, Hai T, Kalhor, Neda, Khan, Md Abdul Wadud, Gibbons, Don L, Blumenschein, Jr, George, Walsh, Garrett L, Reuben, Alexandre, Lu, Charles, Glisson, Bonnie S, Haymaker, Cara, Leung, Cheuk H, Godoy, Myrna C B, Hofstetter, Wayne L, Sepesi, Boris, Ajami, Nadim J, Cascone, Tina, Solis, Luisa M, Tsao, Anne S, Parra, Edwin R, Federico, Lorenzo, Sharma, Padmanee, Futreal, Andrew, Mott, Frank E, Pataer, Apar, Lin, Heather Y, Vaporciyan, Ara A, Lee, J Jack, Kadara, Humam, Zhang, Jianjun, Le, Xiuning

2021

Overview

Ipilimumab improves clinical outcomes when combined with nivolumab in metastatic non-small cell lung cancer (NSCLC), but its efficacy and impact on the immune microenvironment in operable NSCLC remain unclear. We report the results of the phase 2 randomized NEOSTAR trial (NCT03158129) of neoadjuvant nivolumab or nivolumab + ipilimumab followed by surgery in 44 patients with operable NSCLC, using major pathologic response (MPR) as the primary endpoint. The MPR rate for each treatment arm was tested against historical controls of neoadjuvant chemotherapy. The nivolumab + ipilimumab arm met the prespecified primary endpoint threshold of 6 MPRs in 21 patients, achieving a 38% MPR rate (8/21). We observed a 22% MPR rate (5/23) in the nivolumab arm. In 37 patients resected on trial, nivolumab and nivolumab + ipilimumab produced MPR rates of 24% (5/21) and 50% (8/16), respectively. Compared with nivolumab, nivolumab + ipilimumab resulted in higher pathologic complete response rates (10% versus 38%), less viable tumor (median 50% versus 9%), and greater frequencies of effector, tissue-resident memory and effector memory T cells. Increased abundance of gut Ruminococcus and Akkermansia spp. was associated with MPR to dual therapy. Our data indicate that neoadjuvant nivolumab + ipilimumab-based therapy enhances pathologic responses, tumor immune infiltrates and immunologic memory, and merits further investigation in operable NSCLC.

• Publisher: Nature Publishing Group
• Subject: Adult / Aged / Antineoplastic Combined Chemotherapy Protocols - administration & dosage / Biomarkers, Tumor - metabolism / Cancer therapies / Carcinoma, Non-Small-Cell Lung - drug therapy / Carcinoma, Non-Small-Cell Lung - metabolism / Chemotherapy / Drug therapy / Effector cells / Female / Humans / Immunological memory / Immunotherapy / Ipilimumab / Ipilimumab - administration & dosage / Lung cancer / Lung cancer, Non-small cell / Lung Neoplasms - drug therapy / Lung Neoplasms - metabolism / Lymphocytes / Lymphocytes T / Male / Memory cells / Metastases / Microenvironments / Middle Aged / Monoclonal antibodies / Neoadjuvant Therapy / Nivolumab - administration & dosage / Non-small cell lung carcinoma / Patients / Small cell lung carcinoma / Surgery / Targeted cancer therapy / Testing / Tumors