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The Clinical Value of Comprehensive Genomic Profiling


Expert perspective on clinical and personal improvements in cancer care made available by appropriate use of comprehensive genomic profiling.


David R. Gandara, MD: The value of comprehensive genomic profiling can’t be overstated. Non–small cell lung cancer is a poster child for the use of broad-based testing, but this is coming on rapidly and strongly in several other tumor types. Let’s say you’re a practicing oncologist. You’re seeing a new patient with stage IV adenocarcinoma of the lung. Your choices are to treat empirically—with immunotherapy plus or minus chemotherapy, more the combination of chemotherapy and immunotherapy—or to wait until the results of the next-generation sequencing come back. Having a rapid turnaround time facilitates that.

The mistake that’s made is the patient is started on immunotherapy and chemotherapy before the results of the molecular testing come back. When it does come back, it shows a highly favorable oncogene, such as an EGFR mutation. The problem then is stopping the immunotherapy component and starting the patient on the TKI [tyrosine kinase inhibitor] because growing evidence suggests that the efficacy of the TKI is not only diminished by that prior exposure even briefly to checkpoint immunotherapy, but the adverse-effect profile of the TKI is also increased. For instance, interstitial pneumonitis. All the guidelines recommend waiting if possible. If it’s a true emergency, rapidly progressive disease, or falling performance status, an oncologist needs to start treatment emergently. This is less than 10% in advanced-stage non–small cell lung cancer. The recommendation is to start with chemotherapy alone, so you avoid that subsequent negative interaction if you have to switch to a TKI.

For a newly diagnosed patient with advanced-stage non–small cell lung cancer, once I explain to them that we have a variety of options for their treatment and some of these could be quite effective. If we find an abnormality in the cancer that’s specific to them, we’ll be able to individualize therapy, and this will be a much better outcome. There’s a better chance of them responding even in the long term. When I tell them that, I say that we could start empirical therapy, but I don’t recommend that. I recommend we do the testing and wait, and 100% of patients say, “I want something for me.” In other words, that’s why I came to you: I want precision medicine. They may say personalized medicine or individualized. Patients are very proactive about this. Before we had liquid biopsy and we said, “We’re going to send off your tissue.” We don’t know if it’s adequate or if we’re going to need a new biopsy. Even then, they were enthusiastic about it. But if I say, “I’m going to send you downstairs, and we’re going to draw a tube of blood today,” and I expect the results within 1 week, that’s incredible. Patients are the biggest advocate for this testing.

Transcript edited for clarity.

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