The SELECT Trial and Differentiated Thyroid Cancer - Episode 4
An overview of how SELECT trial data affected clinical treatment practice for patients with differentiated thyroid cancer.
Lori Wirth, MD: The SELECT trial was a randomized phase 3, multicenter international trial that enrolled almost 400 patients with iodine-refractory DTC [differentiated thyroid cancer] that was progressive within the 14 months prior to enrollment based on RECIST criteria. Patients were randomized to receive lenvatinib vs a placebo in a 2:1 fashion. The patients were followed until they had disease progression that was centrally confirmed, and then when patients were found to have disease progression based on RECIST, they were unblinded. Those that were found to have been on placebo were then allowed crossover to receive the active lenvatinib therapy. The primary end point for the trial was progression-free survival.
In terms of the outcomes, there was a very significant progression-free survival benefit. The placebo arm had a PFS [progression-free survival] of less than 4 months, whereas an updated analysis of the primary end point showed a progression-free survival of 19 months in the patients that were initially randomized to lenvatinib. That significant PFS benefit did lead to FDA approval of lenvatinib for the treatment of iodine-refractory DTC.
At the time, there had been 1 other drug, sorafenib, that had also been FDA approved for the treatment of the same patient population approximately a year earlier. When lenvatinib became available to our patients, it became the go-to drug because of its significant PFS benefit. It’s also worth noting that the overall response rate in the SELECT trial to lenvatinib was 65%. That kind of overall response rate is very good in oncology. We can’t compare the 2 trials—the randomized trial with lenvatinib and the randomized trial with sorafenib—from any statistically significant point of view. The efficacy benefits with SELECT did seem to be greater than those that were seen in the randomized phase 3 trial studying sorafenib.
It was the basis of those initial data that the SELECT trial did change practice; lenvatinib became the go-to therapy for patients with progressive iodine-refractory DTC. One thing I’ll say about changing practices is we realize in the field that these VEGFR multikinase inhibitors do have some adverse events [AEs] associated with them. There is a class-effect AE profile that includes adverse effects such as hypertension, diarrhea, weight loss, and fatigue. These can impact patients while they’re on therapy, particularly if the duration of responses is as long as it is with a drug like lenvatinib.
One additional concern that has emerged in the last few years is a sensitivity to concern for the adverse-effect profile and the impact on patients’ quality of life. Many providers have begun to think about when to initiate a drug like lenvatinib, particularly in patients who have slow-growing disease and are asymptomatic. I can tell you from experience, it’s a difficult decision that needs to be made on a patient-by-patient basis. Some patients are willing to tolerate adverse effects, particularly if there’s positive activity and the drug might help them live longer. Other patients don’t have as much willingness to tolerate an impact on their quality of life. We must be able to talk about our patients and weigh the pros and cons of starting therapy earlier vs holding off and starting therapy a little later.
Transcript edited for clarity.