作者：广东省肺癌研究所 杨学宁 & LAMP

21. Updated Results of a Multi-Center Phase II Trial of Neoadjuvant Atezolizumab in Resectable Stages IB-IIIB Non-Small Cell Lung Cancer (NSCLC)

*Jay M. Lee1, Alan Nicholas2, James M. Isbell3, *Daniela Molena3, *G. Alexander Patterson4, *Benjamin D. Kozower4, *Varun Puri4, Eric M. Toloza5, Jae Y. Kim6, Dan J. Raz7, Robert E. Merritt8, David J. Finley9, Ciaran J. McNamee10, *Frank A. Baciewicz, Jr.11, Justin D. Blasberg12, John D. Mitchell13, *Michael J. Weyant13, Christopher Scott13, *Harvey I. Pass14, Ann Johnson2, See Phan2, Katja Schulze2, Paul A. Bunn13, Fred R. Hirsch13, Bruce E. Johnson10, Mark G. Kris3, David J. Kwiatkowski10, Ignacio I. Wistuba15, David P. Carbone16, *Valerie W. Rusch3 
1University of California, Los Angeles, CA;2Genentech, South San Francisco, CA;3Memorial Sloan Kettering Cancer Center, New York, NY; 4Washington University, Saint Louis, MO;5H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL;6City of Hope Cancer Center, Duarte, CA;7City of Hope Cancer Center, Los Angeles, CA;8The Ohio State University-Wexner Medical Center, Columbus, OH;9Dartmouth-Hitchcock Medical Center, Lebanon, NH;10Brigham and Women's Hospital, Boston, MA;11Wayne State University/Harper University Hospital/Sinai-Grace Hospital, Detroit, MI;12Yale University - Yale New Haven Hospital, New Haven, CT;13University of Colorado, Aurora, CO;14New York University Medical Center, New York, NY;15The University of Texas MD Anderson Cancer Center, Houston, TX;16The Ohio State University, Columbus, OH

Invited Discussant: *David H. Harpole
  Objective: Immune checkpoint inhibitors are now standard first line therapy for metastatic NSCLC, but their role as neoadjuvant immunotherapy in resectable NSCLC remains undefined. We report the updated safety results of the first large multicenter trial assessing neoadjuvant atezolizumab (PD-L1 inhibitor) for resectable NSCLC.
  Methods: Eligible patients with preoperative stage IB-IIIB resectable NSCLC received 2 cycles of neoadjuvant atezolizumab (1200 mg days 1, 22) followed by surgical resection (day 40±10). Pre- and post-treatment PET/CT, pulmonary function tests, and bio-specimens (tumor, lymph node, and blood) were obtained. The primary endpoint was major pathologic response (MPR; defined as<10% viable tumor in resected specimen). Secondary endpoints were safety, radiographic response (RECIST 1.1), biomarker assessment, overall and disease-free survival. Adverse events (AE) were recorded according to CTCAEv.4.0. Preoperative treatment-related (TR) AE (preop-TRAE) and postoperative TRAE (postop-TRAE; defined as AE onset on or after date of surgery) were analyzed.
  Results: Of 180 planned patients, as of October 2018, 114 are currently accrued with follow-up data to post-surgery visit available on 54: mean age 65.1 years; 35/54(64.8%) non-squamous histology and 35/54(64.8%) ECOG-0 status; and tumor clinical stages (intent to treat) IB, IIA, IIB, IIIA, and IIIB (9.3, 20.1, 24.1, 37.0, and 9.3%, respectively). Two cycles of atezolizumab were completed in 52/54(96%) patients and 1 cycle in 2/54(3.7%) due to AE (grade 2 dyspnea and grade 1 pyrexia). Resection was not performed due to disease progression or other reasons in (4/54;7.4%), and 3/54 patients (5.5%) were deemed unresectable intraoperatively. Surgery was delayed (outside of 10 day window) in 2/54(3.7%) patients due to treatment-related AEs (hypothyroidism and pneumonitis). Intraoperative vascular complications occurred in 2/49(4.1%). Hilar fibrosis was noted in 11/49(22.4%).
Conclusions: Neoadjuvant atezolizumab for patients with stages IB-IIIB NSCLC was remarkably well tolerated, rarely delaying surgery, or interfering with the technical aspects of resection. Accrual continues to assess MPR, survival, and other secondary endpoints.

Table 1