Corey J. Langer, MD, Director of Thoracic Oncology and Professor of Medicine at the Hospital of the University of Pennsylvania, Philadelphia, discussed the OAK study with The ASCO Post.

Robust Data

“In some ways, the OAK data are some of the most robust we have seen in the second-line setting. For the first time, we are seeing a fairly clear-cut survival benefit in programmed cell death ligand 1 (PD-L1)–negative patients (hazard ratio [HR] = 0.75), and we are clearly identifying a benefit in never-smokers (HR = 0.71). We have to drill down to those subpopulations." Dr. Langer commented.

"These are expensive drugs," he added. "If they are not going to do any better in some subsets than chemotherapy alone, particularly now that some chemotherapy agents are no longer on patent, can we justify using them?”

Dr. Langer also noted that the every-3-week dosing schedule of atezolizumab (Tecentriq) could give it preference over every-2-week nivolumab (Opdivo) in the second-line setting. In addition to being more “user friendly,” this schedule will “dovetail nicely” with chemotherapy and possibly with future immunotherapy combinations, he pointed out.

Additional Markers Needed

Martin Reck, MD, PhD, Chief Oncology Physician in the Department of Thoracic Oncology at Lung Clinic Grosshansdorf, Germany, who led the KEYNOTE-029 trial of first-line pembrolizumab (Keytruda), which was also presented at the European Society for Medical Oncology (ESMO) Congress, commented, “This is a very important piece of information on the role of PD-L1/programmed cell death protein 1 (PD-1) antibodies in the treatment of non–small cell lung cancer and confirms the overall survival benefits shown in the POPLAR and CHECKMATE trials. Interestingly, the study also showed an improvement in overall survival, even in patients with no PD-L1 expression, which means we have a problem with using PD-L1 negativity as an exclusion factor for ­treatment.”

In some ways, the OAK data are some of the most robust we have seen in the second-line setting. For the first time, we are seeing a fairly clear-cut survival benefit in PD-L1–negative patients, and we are clearly identifying a benefit in never-smokers.

— Corey J. Langer, MD

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He added, “My suggestion would be that PD-L1 is perhaps one imperfect surrogate marker to describe the activity. It’s a good enrichment factor, but we need additional markers for the characterization of patients who might not benefit from this treatment or who might really benefit.”

It is important to note that the companion diagnostics of atezolizumab (PD-L1 testing) in this trial were different from those of other anti–PD-1/anti–PD-L1 agents, Dr. Reck told The ASCO Post. PD-L1 was tested in tumor cells (1–3) and immune cells (1–3). The results should be reported with this scoring system, he explained, because the scoring values differ from those of PD-L1 expression status measured by the anti–PD-1 antibody ­pembrolizumab. ■