Close-up on HER2 alterations in advanced NSCLC

The National Comprehensive Cancer Network and International Association for the Study of Lung Cancer have said there may be advantages to doing tissue and liquid characterization in parallel, he said. “But everything comes with a cost, and in our institution, tissue assay is still preferable, particularly in the initial diagnosis. But we are starting to do more and more liquid biopsies in parallel.”

In disease monitoring, liquid has potential benefits, though more data are needed to show advantages over imaging and other modalities, he said. In therapy, too, “its clinical relevance is still to be demonstrated in clinical research.”

The AMP/ASCO/CAP guideline for interpreting and reporting sequence variants says tier one (variants with strong clinical significance) and tier two (variants with potential clinical significance) biomarker status should be reported with an interpretive comment, and HER2 mutations are currently a tier two biomarker in metastatic NSCLC, with level C evidence, defined as: “FDA-approved therapies for different tumor types or investigational therapies. Multiple small published studies with some consensus” (Li MM, et al. J Mol Diagn. 2017;19[1]:4–23).

Reporting of HER2 mutation status should be uniform, contain consistent nomenclature, and include the key information needed to inform clinical decisions. “And, yes, reports should show HER2 mutation status alongside driver mutations and actionable biomarkers,” Dr. Hirsch said. NGS reports should be annotated properly in the electronic health record. And if reports are from an external laboratory, the HER2 mutation status should be noted or highlighted in the list of other clinically relevant biomarkers for patients with metastatic NSCLC.

Dr. Hirsch said he found “shocking” the MYLUNG Consortium data, reported in 2021 at the virtual ASCO annual meeting and most recently in Lung Cancer (Robert NJ, et al. Lung Cancer. 2022;166:197–204), that only 46 percent of patients with metastatic NSCLC had five or more guideline-recommended biomarker results available before first-line treatment was selected. “For me personally,” he said, “it was a shocking experience to learn that testing for five important predictive biomarkers when we have approved drugs occurs in less than 50 percent of patients with advanced NSCLC.”

Within the US Oncology Network of more than 1,000 providers, 90 percent of patients were found to have had at least one test performed for ALK, BRAF, EGFR, ROS1, or PD-L1, according to the MYLUNG (Molecularly Informed Lung Cancer Treatment in a Community Cancer Network) Consortium data presented in 2021. But only 46 percent had testing for all five.

In a poster session at this year’s ASCO annual meeting in June, further findings were reported (Robert NJ, et al. J Clin Oncol. 2022;40[suppl 16]:91300. doi:10.1200/JCO.2022.40.16_suppl.9130). In a retrospective observational chart review study of patients with metastatic NSCLC whose first-line treatment was initiated between April 1, 2018 and March 31, 2020, MYLUNG Consortium researchers examined patient factors associated with rates of biomarker testing. They concluded: “Black or African American race, smaller practice size, Southern practice, and squamous cell histology were significantly associated with lower comprehensive biomarker testing rates.”

“We need to act on it, and we need to act very quickly,” Dr. Hirsch said of the data reported in 2021. “There is a clear need for education, particularly in community practices,” he said. “That is very clear. Most of our patients today, if not all, should have molecular testing.”

“So the bottom line: education, education, education. I cannot repeat it enough.”

Sherrie Rice is editor of CAP TODAY. The full webinar is at captodayonline.com.