Single-agent atezolizumab appeared safe and effective across lines of therapy in patients with PD-L1–expressing non–small cell lung cancer, according to results from the global, multicenter, single-arm, open-label phase 2 BIRCH trial.
PD-L1 status may serve as a predictive biomarker to identify patients more likely to benefit from atezolizumab (Tecentriq, Genentech), according to the researchers.
Atezolizumab is the first anti–PD-L1 antibody to demonstrate efficacy in both chemotherapy-naive and previously treated advanced NSCLC.
Previous studies demonstrated that PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC) may be an independent predictor of patient responses to atezolizumab, and that the drug’s efficacy increased with PD-L1 expression.
Felip, MD, PhD, head of the lung cancer unit in the oncology department at Vall d’Hebron University Hospital in Barcelona, and colleagues evaluated the safety and efficacy of atezolizumab in 659 patients (median age, 64 years) with PD-L1–selected locally advanced or metastatic NSCLC.
Patients received 1,200 mg IV atezolizumab every 3 weeks for a median duration of 4.2 months (median number of doses, 7). Patients received atezolizumab as first-line (cohort 1; n = 139), second-line (cohort 2; n = 268) and third-line or higher (cohort 3; n = 252) therapy.
Researchers assessed patients’ PD-L1 status at enrollment using the SP142 immunohistochemistry assay (Ventana Medical Systems) to score patients as having expression levels of TC3 ( 50%) or TC2 ( 5% but < 50%) and IC3 ( 10%) or IC2 ( 5% but < 10%).
In total, 46% of patients had TC3 or IC3 tumor PD-L1 status, distributed similarly across cohorts.
Objective response rate served as the primary endpoint. Secondary endpoints included median duration of response, PFS, OS and safety.
In total, 520 patients discontinued treatment due to progressive disease (65%), adverse events (7%), patient decision (3%), protocol deviation (2%) or physician decision (1%).
With a minimum of 12 months of follow-up, the BIRCH trial met its primary objective to demonstrate a significant ORR improvement compared with historical controls.
Cohort 1 demonstrated an independent review facility–assessed ORR of 22% with a 1% complete response rate and 31% ORR in the TC3 or IC3 subgroup. Median duration of response was 9.8 months overall and 10 months for TC3 or IC3 subgroup. Median PFS was 5.4 months (95% CI, 3-6.9), and 20% of patients achieved 12-month PFS.
Cohort 2 demonstrated an ORR of 19% for the whole group — with a 2% complete response rate — and 26% for the TC3 or IC3 subgroup. Median PFS was 2.8 months (95% CI, 1.5-3.9) and 17% of patients achieved 12-month PFS. Median duration of response could not be estimated.
Cohort 3 demonstrated an ORR of 18% with a 2% complete response rate, and a 27% ORR for the TC3 or IC3 subgroup. Median duration of response was 11.8 months overall and 7.2 months for the TC3 or IC3 subgroup. Median PFS was 2.8 months (95% CI, 2.7-3) and 14% of patients achieved 12-month PFS.
Median duration of survival follow-up was 14.6 months (95% CI, 14.3-14.7) for all treated patients.
Patients in cohort 1 achieved the highest median OS (20.1 months; 95% CI, 20.1-not estimable) followed by cohort 2 (15.5 months; 95% CI, 12.3-not estimable) and cohort 3 (13.2 months; 95% CI, 10.3-17.5).
Median OS continued to improve after an updated survival analysis (median duration of survival follow-up, 22.5 months). Researchers reported a median OS of 23.5 months (95% CI, 18.1-not estimable) in cohort 1, 15.5 months (95% CI, 12.3-19.3) in cohort 2 and 13.2 months (95% CI, 10.3-17.5) in cohort 3.
The TC3 or IC3 subgroup in cohort 1 demonstrated the highest median OS (26.9 months; 95% CI, 12-not estimable).
Responses occurred regardless of EGFR or KRAS mutation status.
Treatment-related adverse events included fatigue (19%), diarrhea (11%), nausea (11%) and pruritus (10%).
The most common serious adverse events consisted of pneumonia (4%), dyspnea (3%), pyrexia (3%) and pneumonitis (2%).
The safety profile appeared similar across cohorts and consistent with previous atezolizumab monotherapy trials.
Felip and colleagues noted randomized phase 3 trials are ongoing to compare atezolizumab monotherapy with combination chemotherapy and to compare chemotherapy with and without atezolizumab in patients with chemotherapy-naive advanced NSCLC. – by Kristie L. Kahl
Disclosure: Felip reports consultant/advisory roles with Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Pfizer and Roche; and speaker roles with AstraZeneca, Bristol-Myers Squibb and Novartis. Please see the full study for a list of all other researchers’ relevant financial disclosures.