Patient Selection for TRKi-Larotrectinib


Marcia Brose, MD, PhD:What has been your experience with larotrectinib patients, and which patients would you consider for larotrectinib treatment?

David Hong, MD:I think that kind of speaks to the question of testing. I’m biased, and I’m in a very specialized academic center, The University of Texas MD Anderson Cancer Center. We try to test as many patients as we can for not onlyNTRKfusion but also other molecular alterations. I do think it’s important to be cognizant of that testing. As next-generation sequencing is becoming more common and cheaper, it’s important—particularly in our metastatic cancer patients—that we try to get those profiles. Not only larotrectinib, but—as you know, Marcia, because you’ve been working on many of these other types of new drugs—there are incredible new drugs that are emerging and can target many of these alterations.

In my opinion, most patients with metastatic cancer should be tested first for not onlyNTRKfusion but other alterations. With that said, I understand logistically in the community, and in so many other countries, that that’s not always possible. One of the questions I get oftentimes from community oncologists is, “Whom do I test? Because I can’t test everybody.” One of the things that I think is clear from the data—patients with lung cancer who really have no other alterations,EGFR,ALK/ROS,BRAF, etc.—are worth getting tested. If you’re doing single-analyte testing, it’s worth sending an NGS [next-generation sequencing], a Foundation Medicine panel, or Caris Life Sciences, or whatever to try to figure if this patient really has anNTRKfusion. And I think you’d be surprised if they find it.

Marcia Brose, MD, PhD:Let me just turn that question a little bit around too. Now you have a patient who has aTRKfusion. Are there any patients you wouldn’t treat with larotrectinib? Or are there specific populations you would give it to or not give it to? Or in what setting, first line, second line, third line? And of course, that’s a very global question because it’s going to depend, I’m sure, on tumor type. Can you talk a little bit about that too?

David Hong, MD:The safety profile is so good, and the efficacy is so profound, I almost feel like you cannot help but give this drug. I suspect that if somebody has significant motor dysfunction, it may not be appropriate to give the drug to those patients. The phase II trial allowed even ECOG 3 [Eastern Cooperative Oncology Group] patients on the trial. I remember this dramatic case of a young woman—who had wildly metastatic papillary thyroid cancer, lung, and bone metastases—was in our inpatient service, literally on a PCA [patient-controlled analgesia] pump for pain, and on oxygen. We were able to get her on a trial, and we started her inpatient. A week and a half later, she walked out of that hospital.

Marcia Brose, MD, PhD:That’s incredible.

David Hong, MD:No pain, no oxygen, and she went back to work as a hairdresser for almost a year and a half. She developed progression, but we put her on LOXO-195, which is the next agent in line that targets these alterations and mutations.

Marcia Brose, MD, PhD:What about on the other side? I know that you and your trial had experience with people who had what we would almost consider a neoadjuvant experience. Can you talk a little bit about those patients?

David Hong, MD:The neoadjuvant setting?

Marcia Brose, MD, PhD:Yeah. In other words, when we talk about, “It was such a good safety profile,” people will start asking, “When do we even start?” Do we even wait for people to be as sick as you’re talking about?

David Hong, MD:I think that’s a relevant question. In the pediatric population, not many but some of the children, for example, with infantile fibrosarcoma, were given larotrectinib. With infantile fibrosarcoma usually, you resect the fibrosarcoma. If you can’t—in many cases you can’t—there’s nothing much you can do other than maybe try chemotherapy. In these situations, we did give the drug, and some of these children were actually able to shrink their tumor. Surgical operations were able to be conducted.

Marcia Brose, MD, PhD:That’s amazing.

David Hong, MD:Yeah, it’s complete response. In the adult setting, I’m not entirely sure if that’s feasible at this point. Maybe there will be in some certain settings. For example, salivary mass tumors.

Marcia Brose, MD, PhD:That’s just what I was thinking, yeah.

David Hong, MD:Oftentimes many of the referrals that we received were patients—who could not get resected by surgery because they were just too complex, wrapped around nerves and bundles—and we put them on study and they had significant shrinkage or massive shrinkage. We didn’t necessarily send any of those patients to surgery because they continued to respond. In fact, I remember 1 patient who continued to respond and went into a complete response. He was a patient who could not get surgical resection of his mass tumors.

Down the line a focused study may be able to be conducted. But right now, I think that’s going to be a little bit difficult to do.

Marcia Brose, MD, PhD:Well, with the data it seems that now more and more we might want to start testing people who have large masses, even if it’s resectable, to consider a couple of months of shrinkage, because maybe their surgeries also might not be so disfiguring, especially in that case that you raised.

Transcript edited for clarity.

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