David R Spigel1, Jamie E Chaft2, Scott Gettinger3, Bo H Chao4, Luc Dirix5, Peter Schmid6, Laura Q M Chow7, Rodney J Hicks8, Larry Leon9, Jill Fredrickson9, Marcin Kowanetz9, Alan Sandler9, Roel Funke9, Naiyer A Rizvi10. 1. Sarah Cannon Research Institute, Nashville, Tennessee. Electronic address: dspigel@tnonc.com. 2. Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, New York. 3. Yale School of Medicine, New Haven, Connecticut. 4. Wexner Medical Center, Ohio State University, Columbus, Ohio. 5. Sint-Augustinus Hospital Oncology Center, Antwerp, Belgium. 6. Barts Cancer Institute, London, United Kingdom. 7. University of Washington, Seattle, Washington. 8. Peter MacCallum Cancer Center, Melbourne, Australia. 9. Genentech, Inc., South San Francisco, California. 10. Columbia University, New York, New York.
Abstract
INTRODUCTION: The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti-programmed death-ligand 1 (PD-L1) atezolizumab in advanced NSCLC selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression. METHODS: Patients with PD-L1 TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3 tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into cohort 1 (chemotherapy-naive/>6 months between adjuvant chemotherapy and recurrence), cohort 2 (≥ second-line without brain metastases), or cohort 3 (≥ second-line with treated brain metastases). Patients received 1200 mg atezolizumab on day 1 (21-day cycles). Primary endpoint was investigator-assessed modified Response Evaluation Criteria in Solid Tumors, objective response rate (Response Evaluation Criteria in Solid Tumors v1.1). Secondary endpoints were overall survival, progression-free survival, duration of response, and safety. RESULTS: Patients (N = 138) were enrolled (137 evaluable for response: cohort 1, n = 31; cohort 2, n = 93; and cohort 3, n = 13). Investigator-assessed objective response rate was 32%, 21%, and 23% for cohorts 1, 2, and 3, respectively. Treatment-related adverse events were reported in 81%, 67%, and 69% of patients, respectively, including grade 3-4 treatment-related adverse events in 16%, 19%, and 15%, respectively. Moreover, 88.6% (86 of 97) paired baseline tumor samples had <5% change in TC/IC PD-L1 expression over time. CONCLUSIONS: Atezolizumab monotherapy showed clinical activity in patients with NSCLC, including those with brain metastases; safety was consistent with previous trials. Atezolizumab has completed phase III monotherapy studies in second-line. Front-line trials are ongoing, confirming these favorable results.
INTRODUCTION: The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti-programmed death-ligand 1 (PD-L1) atezolizumab in advanced NSCLC selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression. METHODS:Patients with PD-L1TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into cohort 1 (chemotherapy-naive/>6 months between adjuvant chemotherapy and recurrence), cohort 2 (≥ second-line without brain metastases), or cohort 3 (≥ second-line with treated brain metastases). Patients received 1200 mg atezolizumab on day 1 (21-day cycles). Primary endpoint was investigator-assessed modified Response Evaluation Criteria in Solid Tumors, objective response rate (Response Evaluation Criteria in Solid Tumors v1.1). Secondary endpoints were overall survival, progression-free survival, duration of response, and safety. RESULTS:Patients (N = 138) were enrolled (137 evaluable for response: cohort 1, n = 31; cohort 2, n = 93; and cohort 3, n = 13). Investigator-assessed objective response rate was 32%, 21%, and 23% for cohorts 1, 2, and 3, respectively. Treatment-related adverse events were reported in 81%, 67%, and 69% of patients, respectively, including grade 3-4 treatment-related adverse events in 16%, 19%, and 15%, respectively. Moreover, 88.6% (86 of 97) paired baseline tumor samples had <5% change in TC/ICPD-L1 expression over time. CONCLUSIONS:Atezolizumab monotherapy showed clinical activity in patients with NSCLC, including those with brain metastases; safety was consistent with previous trials. Atezolizumab has completed phase III monotherapy studies in second-line. Front-line trials are ongoing, confirming these favorable results.
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