Using PD-L1 Expression for Lung Cancer Treatment Planning

PD-L1 expression is becoming a main factor in determining the first line of treatment for patients with non-small cell lung cancer (NSCLC), says Matthew D. Hellmann, M.D. However, for patients who relapsed or have small cell lung cancer (SCLC), testing for the biomarker becomes less important.

“Now we’re able to analyze those questions with clinical data,” Hellmann, a medical oncologist at Memorial Sloan Kettering Cancer Center, said during his presentation at the 11th Annual New York Lung Cancer Symposium™. “Now PD-L1 testing should be done routinely and is becoming the standard test to determine first-line treatment.”

The remarkable successes of PD-1/PD-L1 blockades in lung cancer discovered in 2012 led to the eventual FDA approval of three immunotherapy drugs — Keytruda (pembrolizumab), Yervoy (ipilimumab) and Opdivo (nivolumab). Now, researchers must gain a firmer grasp on the predictors and determinants of response to these agents to personalize treatment plans that will lead to better outcomes, factoring in PD-L1 expression, mutation burden and gene expression analysis.

In Hellman’s practice, testing for PD-L1 is routine in patients with newly diagnosed NSCLC. Patients with more than 50 percent expression are started on Keytruda, which is an anti—PD-L1 agent.

However, the jury is still out on whether patients need to be retested if they relapse to help determine their next line of treatment. Hellmann says it is unnecessary because the majority of patients’ PD-L1 expression does not change over time.

“Somewhat surprising to me, PD-L1 [expression] across space and time is fairly stable,” he said.

In fact, in a set of 57 patients with NSCLC who had EGFR mutations and were tested for PD-L1 expression before and after TKI treatment, 72 percent saw no change. Also, in the KEYNOTE-010 study presented at the 2016 American Society for Clinical Oncology (ASCO) Annual Meeting, the percentage of patients with more than 50 percent PD-L1 expression in archival (456 patients) and new samples (578 patients) was very close (60 percent vs 55 percent).

“The degree of PD-L1 may be more stable than we thought, and archival tissue is probably OK for testing and usage,” Hellman said.

Hellmann also said that PD-L1 testing is not necessary to determine other immunotherapy sequences or combinations in the second-line setting.

“I know some people disagree, I don't think PD-L1 is necessary to inform second-line choice in most cases,” Hellmann said. “One thing I do want to differentiate, is that it's not to say that increased PD-L1 doesn't associate with increased benefit, I think that is true, but it doesn't help me decide whether or not to give second-line therapy as a PD-L1 therapy versus chemo.”

While PD-L1 expression strongly correlates with benefit on frontline Keytruda for patients with NSCLC, Hellmann said that the biomarker is not nearly as predictive for patients with SCLC.

“Nivolumab, with or without ipilimumab, was recently added to the NCCN guidelines for [recurrent] small cell lung cancer based on data from the CheckMate-032 study^. So the question may reasonably come up whether you should be testing patients with small cell lung cancer for PD-L1,” Hellmann said. “The short answer is no.”

“There might be other cells in the tumor microenvironment that are expressing PD-L1, but that's still to be determined,” Hellmann said. "Overall, I think the fair conclusion is that tumor PD-L1 does not seem to be helpful in terms of predicting benefit response in small cell lung cancer and is not a necessary test."

In the current state of newly diagnosed NSCLC, “PD-L1 is here to stay,” Hellmann said. Though determining its role — as well as the role of other biomarkers like EGFR and ALK — in other settings such as SCLC is still yet to be determined as treatment continues to be individualized for patients with lung cancer.

“Part of the job moving forward is to see how do these markers play together?” asked Hellmann. “The progress we’ve made so far is profound, especially for our patients.”