Nick Mulcahy

March 24, 2017

ORLANDO, Florida – It's only March, but the National Comprehensive Cancer Network (NCCN) has already issued five updates of its 2017 non–small cell lung cancer (NSCLC) guidelines, as clinical practice continues to rapidly change, according to presenters here at the group's annual meeting.

"Things are happening very quickly," summarized Wallace Akerley, MD, of the Huntsman Cancer Institute at the University of Utah in Salt Lake City, who was one of three academics who reviewed the state of the art in biomarkers and treatments in NSCLC. "And there will be a lot of changes coming in the future," he added.

The most important change in the use of biomarkers is that all lung cancer patients should now be tested for programmed cell death ligand 1 (PD-L1), said another presenter, Gregory J. Riely, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York City.

"If you are meeting with a new lung cancer patient, you have to do this test to do the right thing," Dr Riely told Medscape Medical News.

If you are meeting with a new lung cancer patient, you have to do this test to do the right thing. Dr Gregory Riely

The guidance was issued by the NCCN at the end of 2016, observed Dr Riely. That was soon after the annual meeting of the European Society of Medical Oncology, where results were presented from the landmark trial that established pembrolizumab (Keytruda, Merck) as superior to standard chemotherapy in the first-line treatment of a specific group of patients with advanced NSCLC, as reported by Medscape Medical News.

The trial, known as KEYNOTE 024, was conducted in untreated patients with advanced NSCLC whose lung cancer biopsy results showed high expression of PD-L1 (≥50% of tumor cells) but no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations.

In these patients, pembrolizumab alone provided superior results to a platinum-containing doublet chemotherapy; median progression-free survival (PFS) was 10.3 vs 6 months (hazard ratio [HR], 0.50).

The secondary endpoint of overall survival (OS) was also significantly improved with pembrolizumab vs chemotherapy. OS at 6 months was 80% vs 72% (HR, 0.60; P = .005).

As a result, the current approach for biomarker testing before any initial treatment of advanced lung cancer is to conduct both molecular analyses and PD-L1 testing, said Dr Reily. The former allows for the identification of targetable mutations, such as EGFR and ALK, and related treatments.

"Biomarker testing for patients with non–small cell lung cancer is critically important, but is a little complicated," he said.

Currently, PD-L1 tests are "all over the map," Dr Riely added, explaining that "everybody has been setting up assays in their lab." In other words, many institutions have decided to do in-house testing instead of sending tissue samples out to a national vendor.

Nevertheless, "there is general concordance of PD-L1 testing," said Dr Riely, who reviewed a study published March 9 in JAMA Oncology that compared four assays that stain for PD-L1 with different antibodies. In that study, there was only one exception to the concordance, he reported, citing the SP142 assay as being the outlier.

Dr Riely also said that new or archival lung tumor samples are equally good for determining expression of PD-L1. "It really doesn't matter," he said.

There is yet another consideration regarding biomarker testing, Dr Riely told the NCCN audience, for NSCLC patients whose tumors are identified as having an EGFR mutation and who are treated with first- or second- generation tyrosine kinase inhibitors (TKIs) but eventually experience clinical progression.

"Test plasma for EGFR T790M," he said. This second round of molecular profiling is needed because EGFR T790M emerges as part of acquired resistance to TKIs.

Among the most recent changes to the NSCLC guidelines is that osimertinib (Tagrisso, AstraZeneca Pharmaceuticals) is now a standard of care for patients with this acquired genetic resistance who had previously been treated with an EGRF inhibitor. In the guidance, this advice moves from a NCCN category 2A to a category 1 recommendation.

Results from the AURA3 trial, presented last October and published simultaneously in the New England Journal of Medicine, showed that in these EGFR T790M patients, osimertinib improved PFS by 5.7 months compared with chemotherapy.

In the guidelines, the same upgrade in category (due to new evidence) also applies to atezolizumab (Tecentriq, Genentech), a PD-L1 inhibitor, for the second- or third-line treatment of NSCLC. The drug was approved for use by the FDA in October of last year.

"Nivolumab, pembrolizumab, and now atezolizumab have similar benefit and toxicity," said Matthew A. Gubens, MD, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, who discussed immunotherapies for lung cancer at the meeting. "Atezolizumab is a worthwhile drug to use in this setting," he summarized.

For once, lung cancer is in the forefront. Dr Matthew Gubens

"This is a talk that couldn't have existed 3 years ago," he also observed, acknowledging rapid change in the field.

Dr Gubens said that lung cancer has long been a forgotten cancer because of the stigma associated with smoking. But he observed that the disease is "immunogenic" and that the new drugs and ongoing clinical trials investigating various combination therapies have generated excitement.

"For once, lung cancer is in the forefront," he said.

Dr Akerley has financial ties with Bristol-Myers Squibb, Genentech, and Novartis. Dr Gubens has ties with multiple pharmaceutical companies, including AstroZeneca, Bristol-Myers Squibb, Merck, Novartis and Pfizer. Dr Riely has disclosed no relevant financial relationships.

National Comprehensive Cancer Network 22nd Annual Conference. Presented March 23, 2017.

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