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)

Solange Peters, Scott Gettinger, Melissa L. Johnson, Pasi A. Jänne, Marina C. Garassino, Daniel Christoph, Chee Keong Toh, Naiyer A. Rizvi, Jamie E. Chaft, Enric Carcereny Costa, Jyoti D. Patel, Laura Q.M. Chow, Marianna Koczywas, Cheryl Ho, Martin Früh, Michel Van Den Heuvel, Jeffrey Rothenstein, Martin Reck, Luis Paz-Ares, Frances A. ShepherdTakayasu Kurata, Zhengrong Li, Jiaheng Qiu, Marcin Kowanetz, Simonetta Mocci, Geetha Shankar, Alan Sandler, Enriqueta Felip*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

214 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2781-2789
Number of pages9
JournalJournal of Clinical Oncology
Volume35
Issue number24
DOIs
StatePublished - Aug 20 2017
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of '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)'. Together they form a unique fingerprint.

Cite this