Atezolizumab as First-Line Therapy for Advanced NSCLC in PD-L1–Selected Patients (BIRCH)
In cohort 1 of the BIRCH study, PD-L1–selected patients met first-line eligibility criteria if they had advanced-stage non–small-cell lung cancer (NSCLC), no central nervous system metastases, and no prior chemotherapy. PD-L1 was centrally evaluated using the Ventana SP142 immunohistochemistry assay. Patients expressing PD-L1 on ≥5% of tumor cells or tumor-infiltrating immune cells were eligible. Patients with EGFR mutation or ALK rearrangement must have had prior tyrosine kinase inhibitor treatment.
Atezolizumab (1200 mg IV every 3 weeks) was administered until radiographic evidence of disease progression or unacceptable toxicity. The primary end point was independently assessed overall response rate (ORR). Secondary end points included investigator-assessed ORR, duration of response, progression-free survival, and overall survival (OS).
After a median follow-up of 22.5 months, median OS was 23.5 months in the intent-to-treat (ITT) population of 138 patients (95% confidence interval [CI], 18.1-NE) and the 1-year OS rate was 66% (95% CI, 58%-75%). Among 73 patients who expressed lower levels of PD-L1, median OS was 23.5 months and 1-year OS was 71%. Among 65 patients who expressed higher levels of PD-L1, median OS was 26.9 months and 1-year OS was 62%.
After a median treatment duration of 8.5 months, investigator-assessed ORR was 25% for the ITT population. ORR was 31% for mutant EGFR patients and 22% for wild-type EGFR patients; 31% for mutant KRAS patients and 22% for wild-type KRAS patients. Median duration of response was 16.5 months (95% CI, 9.9-NE).
No new safety signals were observed. Treatment-related adverse events (AEs) were reported by 60% of the ITT population, of which none was grade 5. Serious AEs were reported in 33%. Atezolizumab was discontinued in 4% of patients due to AEs. The most common AEs (all grades) were fatigue (17%), diarrhea (10%), decreased appetite (9%), nausea (9%), and pruritus (8%).
Researchers concluded that atezolizumab continues to demonstrate durable efficacy in first-line NSCLC, including EGFR and KRAS mutant and wild-type tumors. Phase 3 trials comparing atezolizumab and chemotherapy are underway in first-line NSCLC.
Garassino MC, et al. WCLC 2016. Abstract OA 03.02. ID 4799.