Multikinase Inhibitor Overall Survival Advantage

Marcia Brose, MD: We know from the SELECT data that patients who get lenvatinib in the first setting have a progression-free survival of 18 months. However, patients who get it in the second have a progression-free survival of 15 months. So there is a slight advantage to giving lenvatinib in the first-line setting. That said, lenvatinib can very much be used in the second-line setting. It’s very helpful in that regard.

An interesting thing that also happens with lenvatinib—and can happen with other kinase inhibitors as well, but we use it especially with lenvatinib—is that many times, patients at the time of progression have only 1 type, 1 location that’s actually progressing. If that’s the case, let’s say they have 100 other nodules that are responding well to lenvatinib, it could be deemed that the clinical benefit of lenvatinib still exists if we could just control the progressing site. Sometimes that’s possible. Either using a surgery, ablation, or external beam radiation to a particular site. I’ve had many patients for whom the progression-free survival can be doubled or tripled by managing solitary sites down the line that share progression.

At this point it is very useful to use lenvatinib in the first-line setting, but even in the second-line setting it’s very active. Most important, we can really expand the duration of the clinical value of lenvatinib by salvaging it with external beam radiation to solitary nodules that may not respond when the rest of the disease is doing quite well.

It’s well known that there are not many community oncologists out there who are actually trained in the treatment of thyroid cancer. Certainly it wasn’t around when I was in training. It’s also quite rare for patients with thyroid cancer to need an oncologist. For that reason, the first advice I have for a community oncologists, if possible, is to refer the patient to a specialist who actually has experience with both the thyroid cancer and the use of these agents.

Treating patients with thyroid cancer with these agents, even if they’re used to using these agents in other settings, can be quite different, particularly in regard to the duration of treatment. Because the patients are on these drugs for so long, many times for years, it is very important that the practitioner understands how to mitigate the problems that come from the adverse event, how to mitigate the issues with high blood pressure control, how to mitigate the problems that come with diarrhea, how to not only administer Imodium but make sure the patient is tracking it and doing the education required to be successful. Because it doesn’t really help anybody, including the practitioner and the patient, if the patient is miserable for the entire time they are on therapy.

The goal for the patient really needs to be not only control of their disease but a good quality of life. Those people who are giving it in the community maybe haven’t used lenvatinib very long, but they’re in a place where referral is not possible and the patient can’t travel to a site of expertise. Most important, a tip I can give to a community oncologists is to stay in close contact with your patients. Make sure they know their blood pressure and are taking it reliably for several days before they start. And make sure they take it every day, twice a day, maybe even in the first week, so high blood pressure can be addressed quickly and effectively. If you have a good partnership with your patient, you can expect to have a good outcome with these agents and especially with lenvatinib in this setting.

As far as unmet needs in the future, in spite of the good success and sometimes the 1-year to several-years responses with patients with lenvatinib, eventually patients will actually progress. In the case of sorafenib, there were some data that adding everolimus might actually help. We still have an unmet need of knowing what to do after sorafenib and lenvatinib. An ongoing phase 3 trial is addressing whether cabozantinib, another kinase inhibitor that’s approved for medullary thyroid cancer, might be active in the phase 3 that’s coming and going.

Additional studies are looking at whether adding immunotherapy might be helpful. Again, the data and the verdict for that are out, so we’re looking forward to just hearing from that hopefully in the coming year.

Transcript edited for clarity.