Opinion
Video
Addressing the Impact of Platinum Shortages in mNSCLC Treatment
Experts address the impact of platinum shortages, 4-cycle platinum chemotherapy, and available treatments beyond platinum chemotherapy.
Mark Socinski, MD: In terms of the duration of cytotoxic chemotherapy and platinum-based chemotherapy: Are you a 4-cycle guy?
Martin Dietrich, MD, PhD: Well, you know, we’ve run into a problem in reality, and that is that biomarkers repeat their message between the metastatic and the neoadjuvant space. So in order to buy time, we often give 1 cycle of chemotherapy to allow us to do a biomarker analysis and then, depending on the biomarkers, proceed accordingly. I think that 4 cycles is kind of the standard of care. I wouldn’t necessarily expect that much of a difference. But pragmatically speaking, what we’ve done is we’ve added 1 cycle of chemotherapy without immunotherapy. Got biomarker results. And then as we moved forward, we either augmented to chemo IO [immunotherapy] or, depending on the stage and the biomarker scenario, into other directions. But one of the concerns that we have is that the neoadjuvant data looked so compelling and that we’re closing the door for our targeted therapy. So we’re going to have 2 agents in the near future approved in the adjuvant setting, with osimertinib for EGFR mutations and alectinib for ALK fusions. [And that will make it] very difficult to convince patients—as we do in the metastatic setting—to hold off on immunotherapy until the full biomarker profile is clarified, especially when a patient is interested in going for surgery. And many of these cases are resectable, but just because they’re resectable doesn’t mean that we should resect them. I think the neoadjuvant power of immunotherapy there was remarkably more interesting than the one in the adjuvant setting.
Mark Socinski, MD: Just as an aside. Has the platinum shortage impacted you at all?
Martin Dietrich, MD, PhD: I think it affected all of us. We prioritized it for curative-intent patients. And we certainly made judgment calls about dosing and other factors. But it’s [something] I don’t think that any oncologist really was able to evade completely. We’ve had some adjustments. We used more immunotherapy-only regimens, especially combination immunotherapy-only regimens, so there has been certainly an adaptation. But I think fortunately now at this point we’re beyond that shortage.
Mark Socinski, MD: As you well remember, the IO agents were initially second-line drugs, and we moved them into the first line in combination with the standard chemotherapy…. And there’s been such a change in outcome as a result of combining IO with chemotherapy. The vast majority of trials, with the exception of a few, excluded EGFR, ALK, maybe a few others…. So it was hard to get a sense of the benefit of that approach in the driver population we saw at ASCO [American Society of Clinical Oncology] this year. The keynote, I can’t remember the number [of the study] but [it enrolled patients who were] EGFR mutation positive. So that was essentially a negative trial. There are some nuances about it, but let’s take it as a negative trial. So in your mind, chemo versus chemo plus IO, which do you favor in the driver…population?
Martin Dietrich, MD, PhD: Well, I think it depends on the driver. I think there’s a very clear understanding for me that EGFR in the single-agent PD-1 setting is probably not appropriately matched. Now, you mentioned the exceptions and I only really know of one and that’s the IMPower 150 study that had EGFR and ALK patients included. And I’m not quite sure if it’s the PD-1 or the anti-VEGF impact or the combination of both, and that is really mechanistically driving a benefit. But I think it is a reasonable observation to see this. I think the standard of care is for the most part, if it’s a driver mutation, especially for ALK and not quite as clear for EGFR, to omit the immunotherapy unless it’s a different mutation like a BRAF or a c-MET mutation, which are not really covered by label. But biologically we have some gray zone considerations.
Mark Socinski, MD: Right, and KRAS would be another one of those sorts of things.
Transcript is AI-generated and edited for clarity and readability.
