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Atezolizumab, PD-L1 expression predicts NSCLC overall survival

Patients with non–small cell lung cancer show improved overall survival with atezolizumab, with PD-L1 expression within tumor and tumor-infiltrating immune cells showing this improvement, according to recent research.

“Our data show that atezolizumab provides survival benefit in previously treated patients with non–small cell lung cancer (NSCLC), and that PD-L1 expression on tumour cells and tumour-infiltrating immune cells is predictive of this benefit. Additionally, the exploratory analyses of T-effector and interferon γ gene signature deepens our understanding of mechanisms of response to anti-PD-L1 blockade and provides a starting point for development of future predictive biomarkers for cancer immunotherapies,” Louis Fehrenbacher, MD, from the Kaiser Permanente Medical Center in Vallejo, Calif., and colleagues wrote in their study. “These data, along with those from other atezolizumab studies in patients with previously treated NSCLC, demonstrate the clinical efficacy and safety of targeting PD-L1 with atezolizumab in this patient population.”

Fehrenbacher and colleagues evaluated patients with previously-treated NSCLC who received either atezolizumab (1,200 mg; 144 patients) or docetaxel (75 mg/m²; 143 patients) after successful progression of post-platinum chemotherapy, according to the abstract. Patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, were a minimum of 18 years old, had adequate end-organ and hematological function, and had a measurable disease according to the Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1). The researchers measured baseline PD-L1 expression from immunochemistry in tumor cells as a percentage of the tumor area (TC3 ≥ 50%; TC2 ≥ 5%, < 50%; TC1 ≥ 1%, <5 %; TC0 < 1%), while they measured tumor-infiltrating cells as a percentage of tumor area (IC3 ≥ 10%; IC2 ≥ 5%, < 10%; IC1 ≥ 1%, < 5%; IC0 < 1%).

There was a 12.6-month overall survival for patients in the atezolizumab group (95% CI, 9.7-16.4) compared with a 9.7-month overall survival (95% CI, 8.6-12.0) for patients in the docetaxel group (HR = 0.73; 95% CI, 0.53-0.99; p = 0.04), according to the abstract. Specifically, increased PD-L1 expression was associated with an increase in overall survival, with TC3 or IC3 carrying a hazard ratio (HR) of 0.49 (95% CI, 0.22-1.07; P = 0.068), TC2/3 or IC2/3 carrying an HR of 0.54 (95% CI, 0.33-0.89; P = 0.014), TC1/2/3 or IC1/2/3 carrying an HR of 0.59 (95% CI, 0.40-0.85; P = 0.005) and TC0 and IC0 carrying an HR of 1.04 (95% CI, 0.62-1.75; P = 0.871). Overall, an exploratory analysis showed patients with pre-existing immunity experienced improved survival.

Regarding adverse events, there were 11 patients (8%) in the atezolizumab group and 30 patients (22%) in the docetaxel group who discontinued the study due to experiencing adverse events. There were 16 patients (11%) and 52 patients (39%) who experienced grade 3 or grade 4 adverse events in the atezolizumab and docetaxel groups, respectively, while 1 patient (< 1%) in the atezolizumab group and 3 patients (2%) in the docetaxel groups died during the study period, according to the abstract.

In a related editorial, Egbert F Smit, MD, from the department of pulmonary diseases, Vrije Universiteit in Amsterdam, Netherlands and Michel M van den Heuve, MD, PhD, from the department of thoracic oncology at the Netherlands Cancer Institute in Amsterdam, Netherlands, noted that PD-L1 shows promise as the next immunotherapy target for clinical practice.

“Given the fact that toxicities of treatment with atezolizumab are significantly less as compared with docetaxel treatment and both treatments have a similar survival, in patients tested PD-L1 negative in the clinic one may favour treatment with atezolizumab over docetaxel,” Smit and van den Heuve wrote. “The wide range of PD-L1 assays that have been validated as compendium diagnostics for immune checkpoint inhibitors will make a rigorous comparison necessary, and the outcomes of the Blueprint initiative to compare these assays and antibodies, led by International Association for the Study of Lung Cancer and American Association for Cancer Research, are eagerly awaited.” – by Jeff Craven

Disclosure: Ballinger is a paid employee of Genentech and holds stock in Roche, Exelixis, and Sunesis. The other researchers report various relevant financial disclosures. Please see the full study for a complete list of disclosures.