Surgical results of the Lung Cancer Mutation Consortium 3 trial: A phase II multicenter single-arm study to investigate the efficacy and safety of atezolizumab as neoadjuvant therapy in patients with stages IB-select IIIB resectable non–small cell lung cancer

• Published in: The Journal of thoracic and cardiovascular surgery Vol. 165; no. 3; pp. 828 - 839.e5
• Main Authors: Rusch, Valerie W., Nicholas, Alan, Patterson, G. Alexander, Waqar, Salama N., Toloza, Eric M., Haura, Eric B., Raz, Dan J., Reckamp, Karen L., Merritt, Robert E., Owen, Dwight H., Finley, David J., McNamee, Ciaran J., Blasberg, Justin D., Garon, Edward B., Mitchell, John D., Doebele, Robert C., Baciewicz, Frank, Nagasaka, Misako, Pass, Harvey I., Schulze, Katja, Johnson, Ann, Bunn, Paul A., Johnson, Bruce E., Kris, Mark G., Kwiatkowski, David J., Wistuba, Ignacio I., Chaft, Jamie E., Carbone, David P., Lee, Jay M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2023
• Subjects: Aged; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; ErbB Receptors; Female; Humans; Immune Checkpoint Inhibitors; immunotherapy; lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - surgery; Male; Middle Aged; Mutation; neoadjuvant therapy; Neoadjuvant Therapy - adverse effects; Receptor Protein-Tyrosine Kinases; ALK; VATS; RECIST; AE; NSCLC; OS; IO; neoadjuvant therapy; EGFR; LCMC; MPR; lung cancer; DFS; CT; DLCO; MIS; immunotherapy; PD-L1; FEV1; R0; PFT
• DOI: 10.1016/j.jtcvs.2022.10.007
• EISSN: 1097-685X
• ISSN: 0022-5223; 1097-685X

Multimodality treatment for resectable non–small cell lung cancer has long remained at a therapeutic plateau. Immune checkpoint inhibitors are highly effective in advanced non–small cell lung cancer and promising preoperatively in small clinical trials for resectable non–small cell lung cancer. This large multicenter trial tested the safety and efficacy of neoadjuvant atezolizumab and surgery.
Patients with stage IB to select IIIB resectable non–small cell lung cancer and Eastern Cooperative Oncology Group performance status 0/1 were eligible. Patients received atezolizumab 1200 mg intravenously every 3 weeks for 2 cycles or less followed by resection. The primary end point was major pathological response in patients without EGFR/ALK+ alterations. Pre- and post-treatment computed tomography, positron emission tomography, pulmonary function tests, and biospecimens were obtained. Adverse events were recorded by Common Terminology Criteria for Adverse Events v.4.0.
From April 2017 to February 2020, 181 patients were entered in the study. Baseline characteristics were mean age, 65.1 years; female, 93 of 181 (51%); nonsquamous histology, 112 of 181 (62%); and clinical stages IIB to IIIB, 147 of 181 (81%). In patients without EGFR/ALK alterations who underwent surgery, the major pathological response rate was 20% (29/143; 95% confidence interval, 14-28) and the pathological complete response rate was 6% (8/143; 95% confidence interval, 2-11). There were no grade 4/5 treatment-related adverse events preoperatively. Of 159 patients (87.8%) undergoing surgery, 145 (91%) had pathologic complete resection. There were 5 (3%) intraoperative complications, no intraoperative deaths, and 2 postoperative deaths within 90 days, 1 treatment related. Median disease-free and overall survival have not been reached.
Neoadjuvant atezolizumab in resectable stage IB to IIIB non–small cell lung cancer was well tolerated, yielded a 20% major pathological response rate, and allowed safe, complete surgical resection. These results strongly support the further development of immune checkpoint inhibitors as preoperative therapy in locally advanced non–small cell lung cancer.