This is the first time we have seen data from the BIRCH trial in these three different cohorts using biomarker expression on tumor cells and immune cells,” said formal discussant Luis Paz-Ares, MD, Professor Medicine at the Hospital Universitario 12 de Octubre, Madrid, Spain.

“BIRCH confirms the activity and safety of atezolizumab [formerly known as MPDL3280A] in a large selected cohort of NSCLC [non–small cell lung cancer] patients.”

“Results support previously reported data showing higher response rates with atezolizumab associated with higher intensity expression of PD-L1 staining: 27% vs 17% with less intensity of staining. Survival is good and consistent with prior data with atezolizumab. The survival data are consistent with nivolumab [Opdivo] and pembrolizumab [Keytruda] in first-line ­studies.”

“Safety of atezolizumab was also confirmed,” he continued, “and is similar to other agents in this class.”

The POPLAR results presented at the 2015 European Cancer Congress have an additional 3 months of follow-up since their first presentation at the 2015 ASCO Annual Meeting. “Overall survival is confirmed, with a 27% improvement for atezolizumab compared with docetaxel. This is similar to the CheckMate 057 trial of nivolumab,” he said. “Both trials show the same hazard ratio of 0.73, and the survival curves separate at 9 months, so two different agents in the same class are similar in different scenarios.”

More on PD-L1 Expression

The question of PD-L1 expression as a biomarker is complicated because of the many different assays and lack of correspondence between different assay cutoff points. In POPLAR, patients who tested negative for PD-L1 did not have a benefit from atezolizumab. Those results are similar to those from the nivolumab Checkmate 057 trial for negative PD-L1 expression.

“One trial confirms the other, even though the definition of biomarker differs,” added Dr. Paz-Ares.

“Patients with staining in [tumor cells] do better than those with staining in [immune cells] in this trial. Having the POPLAR database can shed light on outcomes in terms of staining intensity in [tumor cells] and [immune cells],” he said.

“As with any potential biomarker, this biomarker still needs to be validated in phase III trials,” continued Dr. Paz-Ares.“ A phase III trial of atezolizumab including all-comers is ongoing. In 1 year, we can see if this biomarker is clinically worthy.”  ■

Disclosure: Dr. Paz-Ares reported no potential conflicts of interest.