Emerging Treatment Paradigms for Advanced Lung Cancer - Episode 15

Available Therapies for ALK-Rearranged NSCLC


Mark A. Socinski, MD: Yeah. Before we close, I want to get a perspective on the ALK-positive patient. And I’m going to ask MJ, in my practice alectinib is the standard of care for the newly diagnosed ALK patient. You agree or disagree?

Mohammad Jahanzeb, MD: I agree. The NCCN [National Comprehensive Cancer Network] Guidelines have put in now 4 options in the first line and even let crizotinib in those options, which may appear all in the United States. Why would you leave the losing arm, and it wasn’t a close loss by wide margin as an option? But I think NCCN views itself as a global organization and not every country has anything other than crizotinib available. But I think that brigatinib is proving to be a bigger player and we need to wait for maturity of the data to some degree. But if all other things are equal, then everything that equals small things that important I usually say in both cars color is important. So if all other things are equal, taking 4 pills twice a day versus one pill once a day can make that difference.

Mark A. Socinski, MD: Convenience for benefit.

Mohammad Jahanzeb, MD: Yes.

Mark A. Socinski, MD: Others agree, alectinib for the most part?

John V. Heymach, MD, PhD: Yeah, I mean the alectinib data is really fantastic, a huge gain for patients. You know the brigatinib data, what we’ve seen from the ALTA[-1L] first-line study, at least in data that’s been presented so far, the PFS [progression-free survival] for alectinib versus crizotinib was 0.47. For brigatinib it’s 0.49. So those are 2 very similar values. So I agree with MJ’s point that small things may make a difference. But the good news is that we’ve got really good drugs now for first-line therapy.

Mark A. Socinski, MD: A lot of drugs for a small percentage of that population. Leora, we talked a lot about EGFR resistance and that sort of thing. What’s you take on the ALK population in terms of pattern of resistance? Should we be retesting? What should we be looking for, all those sorts of things.

Leora Horn, MD, MSc, FRCPC: So I think we should be retesting. You know we do have lorlatinib now, and if retesting is just not an option, you can’t biopsy, it is the one drug that we know targets D1202R well. And G01202R is the most predominant mechanism that we’re seeing of resistance to alectinib as well as brigatinib. And it’s, it has been up until now the most difficult one to target. I think that if a patient can get a biopsy, be it liquid or tissue, that that would be the preferred thing to do and we can figure out what their mechanism of resistance is, and base on that target the next drug. But it’s, we have lots of different agents to choose from. Luckily, those patients are on therapy so having them hurry up and wait is not as bad. And the NCCN has included lorlatinib as a potential option in that space. So patients who progressed on the second-generation TKI [tyrosine kinase inhibitor].

Transcript Edited for Clarity