MSKCC medical oncologist Dr. Greg Riely explains the growing value of a repeat biopsy after the development of acquired resistance in patients with an EGFR mutation.

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So, after initial therapy with EGFR tyrosine-kinase inhibitors, patients often develop — always, really, develop progressive disease, known as resistance, where the tumor has become resistant to therapy. How we manage patients and how we treat their disease, after development of resistance, is a complicated area. One way we can learn a little bit more about a patient’s tumor, and help to refine our decision making, is to do a biopsy of a site of progressive disease.

What we learn from a biopsy really is two-fold. The first, and easiest part, is the pathologist looks at it under the microscope and says, “is this still non-small cell lung cancer, or is this changed?” A relatively rare phenomenon is transformation of non-small cell lung cancer into small cell lung cancer — it happens maybe one to three percent of the time, but it’s a relevant thing to find, and we would adjust chemotherapy as a consequence of this.

Another thing to look for when we biopsy a site of resistance is acquisition of new mutations. One of the most common new mutations identified, it happens in about two-thirds of patients, is a secondary mutation called T790M. The important thing about identifying T790M is that we can now, in clinical trials, and hopefully in the future, with FDA approved drugs, target that T790M mutation with a new drug; we have two new drugs that are being developed now, one is called rociletinib and one is called mereletinib — these are specifically designed to target T790M. Now, importantly, any given biopsy has a chance of finding a mutation that’s present, and it also has a chance of missing it — whether that’s because we biopsied a site that didn’t have that mutation or, for whatever reason, our testing didn’t identify the T790M mutation. I think it’s important to know that as a caveat before going in to re-biopsy, but I do think that biopsying tumors at the time of resistance to EGFR tyrosine-kinase inhibitors does help devise the next best therapy for a patient.