David L. Rimm, MD, PhD, professor of pathology and of medicine, director of pathology tissue services, director of translational pathology, Yale Cancer Center, discusses the continued role for PD-L1 testing to predict response with checkpoint inhibitors in non&shy;—small cell lung cancer (NSCLC).

PD-L1 IHC 22C3 pharmDx is the first FDA-approved companion diagnostic test for PD-L1 testing in NSCLC. This test, used with pembrolizumab (Keytruda), is going to around for a long time, says Rim. This is because recent data demonstrated that pembrolizumab was more effective than chemotherapy in frontline metastatic NSCLC, but only for patients whose tumors have ≥50% PD-L1 expression. This means that patients will want to have this test to determine if they are a candidate for frontline pembrolizumab, says Rimm. Patients who respond to frontline pembrolizumab may not need chemotherapy for a long time, if ever, he says. This is really a breakthrough in the management of lung cancer, he says. For that reason, PD-L1 testing is not going to go away anytime soon.

The FDA approved pembrolizumab for the frontline treatment of patients with PD-L1 positive, metastatic NSCLC who do not harbor EGFR or ALK aberrations in October 2016.   

The approval was based on data from the phase III KEYNOTE-024 trial, in which single-agent pembrolizumab reduced the risk of death by 40% and improved progression-free survival (PFS) by 4.3 months compared with doublet chemotherapy for untreated patients with advanced NSCLC with PD-L1 expression on ≥50% of cells.

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David L. Rimm, MD, PhD, professor of pathology and of medicine, director of pathology tissue services, director of translational pathology, Yale Cancer Center, discusses the continued role for PD-L1 testing to predict response with checkpoint inhibitors in non&shy;–small cell lung cancer (NSCLC).
 

Dr. David L. Rimm on the Continued Role for PD-L1 Testing in NSCLC

David L. Rimm, MD, PhD, professor of pathology and of medicine, director of pathology tissue services, director of translational pathology, Yale Cancer Center, discusses various options for biomarker testing in lung cancer.

Genomics testing involves an examination of the mutational or neoantigen load, explains Rimm. While this assay does select patients with a high mutational load, Rimm feels that this method is insufficiently sensitive, such that it misses those patients who may not have a high mutational load, but would still benefit from therapy.

Rimm is more optimistic about another form of biomarker testing, which involves looking at the immune cell microenvironment. In this method, one can measure the distribution and properties of T-cells determined by coexpression of other markers.

Dr. Rimm on Biomarker Testing in Lung Cancer

David L. Rimm, MD, PhD, professor of pathology and of medicine, director of pathology tissue services, director of translational pathology, Yale Cancer Center, discusses alternatives to PD-L1 testing to predict response with checkpoint inhibitors in lung cancer.

Around 10% of patients who are PD-L1 negative still show some benefit from a PD-1 inhibitor. A test is needed to identify those patients, says Rimm. There are a number of other potential approaches that are being considered, including genomic approaches, neoantigen-type approaches, and other protein or alternative microenvironment-type approaches.

Genomic and neoantigen approaches are less likely to succeed, say Rimm. A more sensitive, less specific test is preferred, because it is better to treat a few patients that may not respond than it is to be too specific and rule out those who may benefit from an immunotherapy, he says. 

One promising approach is to look at tumor-infiltrating lymphocytes or other cells within the environment of the tumor that may not actually be expressing PD-L1, but are the cells that actually kill the tumor.

David L. Rimm, MD, PhD

Articles

Dr. David L. Rimm on the Continued Role for PD-L1 Testing in NSCLC

Dr. Rimm on Biomarker Testing in Lung Cancer

Dr. David L. Rimm on Alternatives to PD-L1 to Predict Immunotherapy Response in Lung Cancer