Abstract: |
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 (minimumof 20 month follow up) for cohort 1 was 23.5months (26.9months for TC3 or IC3 patients); themedian OS in cohorts 2 and 3 was 15.5 and 13.2months, 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. © 2017 by American Society of Clinical Oncology All rights reserved. |
Keywords: |
immunohistochemistry; adult; cancer chemotherapy; cancer survival; controlled study; protein expression; treatment response; aged; aged, 80 and over; middle aged; major clinical study; overall survival; clinical trial; drug tolerability; fatigue; advanced cancer; diarrhea; drug efficacy; drug safety; monotherapy; side effect; treatment duration; antineoplastic agents; conference paper; cancer staging; outcome assessment; follow up; antineoplastic agent; neoplasm staging; biological marker; progression free survival; phase 2 clinical trial; bleeding; nausea; carcinoma, non-small-cell lung; lung neoplasms; peripheral neuropathy; cohort analysis; monoclonal antibody; alanine aminotransferase blood level; arthralgia; aspartate aminotransferase blood level; asthenia; dyspnea; fever; pneumonia; pruritus; rash; alanine aminotransferase; aspartate aminotransferase; liver failure; biosynthesis; immunology; antibodies, monoclonal; heart failure; multicenter study; tumor cell; colitis; hypothyroidism; lung infection; infusions, intravenous; immunocompetent cell; heart arrest; intravenous drug administration; aspiration pneumonia; cerebrovascular accident; brain infarction; respiratory failure; programmed death 1 ligand 1; non small cell lung cancer; decreased appetite; septic shock; respiratory distress; acute coronary syndrome; response evaluation criteria in solid tumors; very elderly; humans; human; male; female; priority journal; atezolizumab; cd274 protein, human; antigens, cd274; internal hemorrhage
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