Background
BIRCH (NCT02031458) is a single-arm Phase II study of atezolizumab (anti-PDL1) as first-line (1L) or subsequent (2L/3L+) therapy in PD-L1–selected advanced NSCLC. Primary analyses (median follow-up, 8.5 months) demonstrated meaningful ORR benefit in chemotherapy-naive and pre-treated patients. Here, we report updated (> 12 months) efficacy and biomarker data.
Methods
Eligibility criteria included PD-L1–selected stage IIIB/IV or recurrent NSCLC without CNS metastases. Cohort 1 (1L) patients had no prior chemotherapy; Cohorts 2 (2L) and 3 (3L+) patients had progressed on prior platinum. Patients with EGFR mutation had prior TKI treatment. PD-L1 expression was centrally evaluated (VENTANA SP142 IHC assay). Enrolled patients had PD-L1 expressed on ≥5% of tumor cells (TC) or tumor-infiltrating immune cells (IC; TC2/3 or IC2/3). Atezolizumab 1200mg IV was administered q3w until progression or unacceptable toxicity (1L) or clinical benefit loss (2L/3L+). The primary endpoint was independent review facility (IRF)-assessed ORR. Secondary endpoints included investigator (INV)-assessed ORR, DOR, PFS and OS, and exploratory biomarkers.
Results
659 patients in 3 cohorts were evaluable for efficacy. INV-assessed ORR was 24% and 19% for Cohorts 1 and 2/3, respectively (Table). Median (m) DOR was 13.1 months (95% CI, 9.9-17.5) for Cohort 1 and 14.1 months (95% CI, 10.5-NE) for Cohorts 2/3; most responses were ongoing. With a median survival follow-up of 14.6 months, mOS was 20.1 and 14.7 months for Cohorts 1 and 2/3, respectively. Responses occurred across therapy lines regardless of EGFR and KRAS status or tumor histology. Treatment-related adverse events were similar to previous atezolizumab trials and comparable across cohorts; the most common were fatigue (18%) and nausea (10%).
Conclusion
With longer follow-up, atezolizumab monotherapy continues to demonstrate clinical benefit in advanced NSCLC across therapy lines and tumor baseline characteristics. These data support the continued investigation of atezolizumab in previously treated and untreated PD-L1–selected patients.
Tabled
1
| Patients, n | ORR, % (95% CI)a | mPFS, mo (95% CI)a | mOS, mo (95% CI) | |
|---|---|---|---|---|
| All Treated Patients (TC2/3 or IC2/3) | ||||
| Cohort 1 (1L) | 139 | 24% (17-32) | 7.3 (5.6-9.1) | 20.1 (20.1-NE) |
| Cohort 2 (2L) | 268 | 19% (15-24) | 2.8 (2.6-4.1) | 15.5 (12.3-NE) |
| Cohort 3 (3L+) | 252 | 19% (15-25) | 3.0 (2.8-4.1) | 13.2 (10.3-17.5) |
| PD-L1 TC3 or IC3 Subgroup | ||||
| Cohort 1 (1L) | 65 | 32% (21-45) | 7.3 (4.9-12.0) | NE (12.0-NE) |
| Cohort 2 (2L) | 122 | 25% (18-34) | 4.1 (2.6-6.5) | 15.1 (12.0-NE) |
| Cohort 3 (3L+) | 115 | 30% (22-39) | 4.2 (3.0-6.2) | 17.5 (11.1-NE) |
Based on updated data cutoff date of December 1, 2015.
aAssessed by investigator per RECIST v1.1.
NE, not estimable.
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