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)

Publikation

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)

Wissenschaftlicher Artikel/Review - 13.06.2017

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

Zitation

Peters S, van den Heuvel M, Rothenstein J, Reck M, Paz-Ares L, Shepherd F, Kurata T, Li Z, Qiu J, Kowanetz M, Mocci S, Shankar G, Sandler A, Früh M, Ho C, Gettinger S, Johnson M, Jänne P, Garassino M, Christoph D, Toh C, Rizvi N, Chaft J, Carcereny Costa E, Patel J, Chow L, Koczywas M, Felip E. 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). J Clin Oncol 2017; 35:2781-2789.

Art

Wissenschaftlicher Artikel/Review (Englisch)

Zeitschrift

J Clin Oncol 2017; 35

Veröffentlichungsdatum

13.06.2017

eISSN (Online)

1527-7755

Seiten

2781-2789

Kurzbeschreibung/Zielsetzung

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.