Evaluating the Effectiveness of Lenvatinib in a Real-World Study for RAI-Refractory DTC

Francis P. Worden, MD, professor of medicine at the University of Michigan Rogel Cancer Center, Ann Arbor, Michigan, discusses the background of a study evaluating lenvatinib (Lenvima) for the treatment of patients with radioiodine (RAI)-refractory differentiated thyroid cancer, including in those with BRAF-mutated, wild-type and BRAF untested tumors.

Transcription:

0:09 | This was a real-world experience. As background, we know that the SELECT trial [NCT01321554] showed an improvement in progression-free survival over placebo by about 5 times the difference. Since then, there have not been any other agents that have come forward that have been more effective than lenvatinib. Now is the time for us to start looking at lenvatinib in a real-world setting to see how the drug is being used, are the doses appropriate, are [patients] staying on therapy or when are they coming off therapy?

0:52 | Interestingly enough, we noticed overwhelmingly that in our real-world experience that we published at the end of December last year, that the majority of the [patients], when we surveyed providers from all around the country who treat patients [with thyroid cancer] who were refractory to iodine, the starting dose for the vast majority of [patients] was 24 mg, and that response rates were somewhere around 72%, which was higher than in the SELECT trial. That makes sense because we are not actually controlling for the time to progression or the RECIST criteria that is involved in a clinical study. The majority of [patients] were able to maintain their therapy at 24 mg with some dosage adjustments, and then [patients] came off for progression or for toxicity. This told us that the drug is being used appropriately and [patients] are garnering a response from a treatment when they have RAI-refractory disease.

2:02 | The big controversy now in thyroid cancers when they become refractory is treatment. We now know from next-generation sequencing assays that we have driver mutations that are mutually exclusive. In papillary thyroid cancers, in particular, we know about 50% to maybe 65% or so of patients who have these cancers have a driver mutation that is BRAF. Others include RET, NTRK, [and] RAS...A patient who has a BRAF mutation is going to have these other mutations.

3:00 | With selpercatinib [Retevmo], treating fusions that are RET fusions that are driving differentiated thyroid cancer, or NTRK with the use of larotrectinib [Vitrakvi] or entrectinib [Rozlytrek], we know that we can get nice responses with those drugs and [adverse] effect profiles that are manageable. Oftentimes, those drugs are used first when we identify those driver mutations. There is in some ways a controversy where folks may identify a BRAF mutation and saying now that we have to darafenib [Tafinlar] and tremetinib [Mekinist] available by an agnostic approval from the FDA for patients who have BRAF V600E-driven tumors that we can use these.

4:05 | However, a study done out of MD Anderson, a multicenter study, showed that response rates either with darafenib plus trametinib or darafenib by itself are somewhere between 30% and 35% as compared to the 60% or 70% that we see with lenvatinib. So, the question comes up, is it better to use lenvatinib in someone who is BRAF-positive vs automatically going to a MEK inhibitor and a BRAF inhibitor? That was kind of the background to this study.