Advances in Targeted Therapies for Non-Small Cell Lung Cancer - Episode 3

Broad Molecular Testing Use in Adenocarcinoma versus Squamous Cell Carcinoma

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Drs Shiller and Piotrowska discuss use of broad genomic profiling according to the patient’s histologic subtype of NSCLC.

Joel Neal, MD, PhD: As we think about these biomarkers in lung cancer, what do we notice? What's our pre-test probability of thinking about whether patients have actionable biomarkers early on in the diagnosis? Dr Piotrowska, Zosia, what do you think about in terms of adenocarcinoma versus squamous and ordering these complex next generation panels that Michelle talked about?

Zosia Piotrowska, MD: I think many of these biomarkers are most commonly seen in adenocarcinomas. We certainly know that to be true for EGFR and ALK and ROS1 and the KRAS mutations and others. The guidelines say absolutely it's essential to do broad molecular testing in patients with advanced adenocarcinoma, but I would say that some of these can arise in squamous cell carcinomas as well. We rarely but can see mutations in EGFR and ALK and others in squamous cell carcinomas. Sometimes these are tumors that are more of an adenosquamous histology where we may sample a site that's squamous but there may be other parts of the tumor that are adenocarcinoma. Some of the other markers like MET exon 14 skipping for example can be seen in various histologies: adenocarcinoma, squamous, sarcomatoid. In my practice I actually generally will think about ordering broad molecular testing in all of my non-small cell lung cancer patients regardless of histology whether it be adenocarcinoma or squamous cell carcinoma. I think it's especially important if you have patients with squamous cell carcinoma who may have some kind of unusual demographics for example a light or no smoking history, younger age, and things like that. Really, I don't think in this day and age, one should be faulted for ordering broad molecular testing in advanced non-small cell lung cancer for any histology. I'm curious how Dr Shiller views that from a path perspective.

Michelle Shiller, DO, AP/CP, MGP: So, I couldn't agree with you more Zosia, and I will say that I'm lucky that where I practice at Baylor [University] that there's a reflex standing order at the time that non-small cell lung cancer is diagnosed, we go ahead and reflex to broad genomic profiling. I do think that represents a best practice and I'll also mention just like what you were saying, there was that paper that was published in the JCO in February of 2022, this year. It was issued as a provisional clinical opinion and was a joint paper for the Association for Molecular Pathology and ASCO [American Society of Clinical Oncology], recommending that all advanced cancers or metastatic cancers see broad genomic profiling. So, a very well written paper, it talks about the economics of it and so on. Certainly, with non-small cell lung cancer that is definitely one where we would expect and hope that that would be something that's embraced throughout the country for any patient who has such a diagnosis so certainly agree with you completely.