Copenhagen, Denmark—Immunotherapy competition in non–small-cell lung cancer (NSCLC) continued to heat up as atezolizumab (Tecentriq) improved overall survival (OS) versus docetaxel, according to results from the randomized, phase 3 OAK clinical trial reported at the 2016 European Society for Medical Oncology Congress by Fabrice Barlesi, MD, Professor of Medicine, Aix-Marseille University, France.
Patients who received the PD-L1 inhibitor had a median OS of 13.8 months compared with 9.6 months in patients who received docetaxel. The data showed a consistent advantage for atezolizumab, regardless of PD-L1 expression status or tumor histology (squamous vs nonsquamous).
Progression-free survival (PFS) did not differ significantly between the treatment groups, but atezolizumab resulted in more objective responses, reported Dr Barlesi.
“This is the first phase 3 study of atezolizumab, and it confirms the efficacy seen in the phase 2 POPLAR study, as well as the results with PD-1 inhibitors,” said Dr Barlesi. “Atezolizumab offers a new second-line therapeutic strategy for patients with non–small-cell lung cancer, regardless of the PD-L1 status of the tumor.”
The results provide additional momentum to the expanding role of immunotherapy in NSCLC, and suggest the emergence of new treatment paradigms for NSCLC, said Naiyer Rizvi, MD, Director of Thoracic Oncology, Columbia University, New York.
“Atezolizumab established a role for second-line treatment in unselected non–small-cell lung cancer,” said Dr Rizvi, who was not involved in the clinical trial. “Pembrolizumab established a role for first-line therapy for PD-L1 selected non–small-cell lung cancer. The first-line space could be expanded with immuno-oncology combinations,” he added.
As Dr Rizvi noted, the phase 2 POPLAR clinical trial demonstrated a survival advantage for patients with previously treated NSCLC who received atezolizumab versus patients who received docetaxel (Fehrenbacher L, et al. Lancet Oncol. 2016;387:1837-1846). This clinical trial also showed an association between PD-L1 expression and the likelihood of response to treatment.
The favorable POPLAR results provided the basis for continuing the investigation of atezolizumab in patients with advanced NSCLC that progressed during or after first-line, platinum-based chemotherapy.
The phase 3 OAK clinical trial involved 1225 patients with previously treated NSCLC. Patient consent was sought for tissue sampling to determine PD-L1 expression status, but patients were not selected on the basis of PD-L1 expression.
Patients received atezolizumab 1200 mg every 3 weeks or docetaxel 75 mg/m2 every 3 weeks. The primary end point was OS.
After a minimum follow-up of 19 months, the data from a preliminary analysis of 850 patients showed a 27% reduction in the survival hazard in favor of atezolizumab (P = .0003). The 12-month OS was 55% with atezolizumab and 41% with docetaxel. In addition, the 18-month OS was 40% with atezolizumab versus 27% with docetaxel.
Analysis of survival by PD-L1 expression showed a 5.4-month OS advantage in favor of atezolizumab in patients with PD-L1 expression ≥1%; the OS was 15.7 months with atezolizumab versus 10.3 months with docetaxel (P = .0102). Patients whose tumors had <1% PD-L1 expression also benefited from atezolizumab, as reflected in a median PFS of 12.6 months with atezolizumab versus 8.9 months with docetaxel (P = .0205).
Patients with higher levels of PD-L1 expression derived even greater benefit from treatment with atezolizumab. In the subgroup of patients with PD-L1 expression of ≥50% in tumor cells or ≥10% expression in immune cells (16% of the study population), the median OS was 20.5 months with atezolizumab versus 8.9 months with docetaxel (P <.0001).
The consistency of benefit in patients with or without PD-L1 positive tumors suggests that “PD-L1 is perhaps one imperfect surrogate marker to describe the activity,” said Martin Reck, MD, Professor of Thoracic Oncology, Lung Clinic Grosshansdorf, Germany. “It’s a good enrichment factor, but we need additional markers for the characterization of patients who may not benefit from this treatment or who may really benefit.”
Patients with nonsquamous tumors had a median OS of 15.6 months with atezolizumab versus 11.2 months with docetaxel (hazard ratio [HR], 0.73; P = .0015). The subgroup of patients with squamous-cell tumors had a median OS of 8.9 months with atezolizumab versus 7.7 months with chemotherapy (HR, 0.73; P = .0383).
The PFS did not differ significantly—a median of 4 months with docetaxel versus 2.8 months with atezolizumab. The objective response rate was higher with atezolizumab for patients with any level of PD-L1 expression, but favored docetaxel in the subgroup of patients who tested negative for PD-L1 expression in tumor cells and immune cells.
Grade 3 or 4 treatment-related adverse events occurred in 15% of patients in the atezolizumab group versus 43% of patients in the docetaxel group.
