Medline ® Abstract for Reference 13
of 'Immunotherapy of non-small cell lung cancer with immune checkpoint inhibition'
Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1-Selected Advanced Non-Small-Cell Lung Cancer (BIRCH).
Peters S, Gettinger S, Johnson ML, Jänne PA, Garassino MC, Christoph D, Toh CK, Rizvi NA, Chaft JE, Carcereny Costa E, Patel JD, Chow LQM, Koczywas M, Ho C, Früh M, van den Heuvel M, Rothenstein J, Reck M, Paz-Ares L, Shepherd FA, Kurata T, Li Z, Qiu J, Kowanetz M, Mocci S, Shankar G, Sandler A, Felip E
J Clin Oncol. 2017;35(24):2781. Epub 2017 Jun 13.
Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non-small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC). Patients and Methods Eligible patients had advanced-stage NSCLC, no CNS metastases, and zero to two or more lines of prior chemotherapy. Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on≥5% of TC or IC (TC2/3 or IC2/3 [TC or IC≥5% PD-L1-expressing cells, respectively]) were enrolled. Atezolizumab 1,200 mg was administered intravenously every 3 weeks. Efficacy-evaluable patients (N = 659) comprised three cohorts: first line (cohort 1; n = 139); second line (cohort 2; n = 268); and third line or higher (cohort 3; n = 252). The primary end point was independent review facility-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors [RECIST]version 1.1). Secondary end points included median duration of response, progression-free survival, and overall survival (OS). Results BIRCH met its primary objective of demonstrating a significant ORR versus historical controls. With a minimum of 12 months of follow-up, the independent review facility-assessed ORR was 18% to 22% for the three cohorts, and 26% to 31% for the TC3 or IC3 subgroup; most responses are ongoing. Responses occurred regardless of EGFR or KRAS mutation status. The median OS from an updated survival analysis (minimum of 20 month follow up) for cohort 1 was 23.5 months (26.9 months for TC3 or IC3 patients); the median OS in cohorts 2 and 3 was 15.5 and 13.2 months, respectively. The safety profile was similar across cohorts and consistent with previous atezolizumab monotherapy trials. Conclusion BIRCH demonstrated responses with atezolizumab monotherapy in patients with PD-L1-selected advanced NSCLC, with good tolerability. PD-L1 status may serve as a predictive biomarker for identifying patients most likely to benefit from atezolizumab.
Solange Peters, Centre Hospitalier Universitaire Vaudois, Lausanne; Martin Früh, Kantonsspital St Gallen, St Gallen, Switzerland; Scott Gettinger, Yale Cancer Center, New Haven, CT; Melissa L. Johnson, Sarah Cannon Research Institute, Nashville, TN; Pasi A. Jänne, Dana-Farber Cancer Institute, Boston, MA; Marina C. Garassino, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Daniel Christoph, Universitätsklinikum Essen, and the Ruhrlandklinik, Universität Duisburg-Essen, Essen; Martin Reck, Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; Chee Keong Toh, National Cancer Centre, Singapore, Singapore; Naiyer A. Rizvi and Jamie E. Chaft, Memorial Sloan Kettering Cancer Center; Jamie E. Chaft, Weill Cornell Medical College, New York, NY; Enric Carcereny Costa, Catalan Institute of Oncology Badalona, Badalona; Luis Paz-Ares, Hospital Universitario Doce de Octubre&IIS i+12, CNIO, Ciberon