Atezolizumab as first-line (1L) therapy for advanced non-small cell lung cancer (NSCLC) in PD-L1–selected patients: Efficacy data from the BIRCH trial

Abstract

Background: Atezolizumab (atezo) inhibits binding of PD-L1 to its receptors, PD-1 and B7.1, restoring tumor-specific T-cell immunity and leaving the PD-L2/PD-1 interaction intact. This single-arm Phase II study (BIRCH; NCT02031458) was designed to evaluate atezo monotherapy in PD-L1-selected patients with advanced NSCLC. A previous analysis (median follow-up, 8.5 months) demonstrated clinical activity in chemotherapy-naive 1L and 2L+ PD-L1-selected patients. Here we present updated efficacy data for 1L patients. Methods: Eligible patients had PD-L1-selected advanced-stage NSCLC, with no prior chemotherapy or CNS metastases. PD-L1 was centrally evaluated using the VENTANA SP142 IHC assay. Enrolled patients expressed PD-L1 on 5% of tumor cells (TC) or tumor-infiltrating immune cells (IC), ie, TC2/3 or IC2/3. Those with EGFR mutation or ALK rearrangement must have had prior treatment with an appropriate TKI. Atezo was administered (1200 mg IV q3w) until radiographic disease progression or unacceptable toxicity. The primary endpoint was independent review facility (IRF)-assessed ORR; secondary endpoints included investigator (INV)-assessed ORR, DOR PFS (RECIST v1.1) and OS. Results: With a median duration of survival follow-up of 22.5 months, INV-assessed ORR was 25% in TC2/3 or IC2/3 (all treated) patients and 34% in TC3 or IC3 patients (Table). Median OS was 23.5 months in all treated patients and 26.9 months in the TC3 or IC3 subgroup. Responses were observed in both EGFR and KRAS mutant and wildtype tumors. The safety profile was consistent with previous atezo NSCLC studies. Conclusions: With a median follow-up of 22.5 months, atezo continued to demonstrate durable clinical benefit in 1L NSCLC, in both EGFR and KRAS mutant and wildtype tumors. These results support ongoing Phase III trials evaluating atezo vs chemotherapy in 1L NSCLC.