The impact of and strategies for addressing less frequent mutations in NSCLC treatment decisions, emphasizing actionable alterations and timely interventions in challenging scenarios.
Charu Aggarwal, MD, MPH: Dr Kaushal [Parikh], I’ll come to you next. Do you actively look for less frequent mutations and fusions when you look at reports? How do you go about interpreting them?
Kaushal Parikh, MD: As far as the actionable mutations are concerned, the uncommon or less common mutations can often still be actionable, as we’ll discuss later. These are even more valuable in the resistant setting after first-line treatment. I have had patients have a BRAF fusion as a resistance mechanism and an EGFR fusion as a resistance mechanism to…the…frontline osimertinib. So these hold more and more value in [the] first test and even more in second- and third-line settings where these patients can develop what may seemingly be not actionable—but is an actionable—alteration, however uncommon it might be.
Charu Aggarwal, MD, MPH: Dr [Nagashree] Seetharamu, are there situations where you will start treatment while you’re waiting for results, and what factors play into your decision to begin?
Nagashree Seetharamu, MD: Great question. So this sometimes happens in a hospital setting when patients are admitted and they’re very sick. The NGS [next-generation sequencing] testing usually takes time, and we may not have time to wait for liquid biopsy results, or it comes back as ND [not detected] as you mentioned. For the most part, I think we’re able to wait until we get the results, but occasionally we may have to act, or we get a result we can’t really rely on like an undetectable type of result, and we may have to get started on some treatment.
Usually in that situation, I start with chemotherapy. I do not add immunotherapy [IO] for the most part. If there’s an actionable mutation that comes along in a subsequent report, then I am much more comfortable switching over. Even in patients who have a known history of tobacco use, patient profiling perhaps may not be the best way because I’ve seen EGFR mutations even in patients who have had significant tobacco use history.
Charu Aggarwal, MD, MPH: I think it’s incredibly important to just reiterate the fact that we should not be basing our treatment results or treatment options on PD-L1 results alone. And I think it’s just incredibly important to use a strategy where you have to come in, maybe use chemotherapy, but hold IO so that we can avoid the risk of IO-related toxicities, especially if we have to be in a situation to introduce a TKI [tyrosine kinase inhibitor]. This has been a great discussion.
Transcript edited for clarity.