Jonathan W. Goldman, MD, on RET Fusion–Positive NSCLC: Adjuvant Selpercatinib

This is a trial of the adjuvant use of selpercatinib. So it's a RET inhibitor, highly active, CNS penetrant, generally well tolerated, and we hope to see whether this could improve event-free survival after surgery for early-stage lung cancer. There were also some patients that received radiation, but the vast majority got surgery as their primary curative-intent therapy. Patients were enrolled and then randomized 1 to 1 to either get placebo or selpercatinib for up to 3 years. The primary endpoint was event-free survival in the stage II and IIIA population, and we had additional endpoints of the overall survival, the event-free survival, and the overall study population, as well as a blinded independent review of this imaging. The trial overall enrolled 151 patients among those in the stage II and IIIA populations. There were 55 in the placebo arm and 54 in the selpercatinib arm. And the hazard ratio for event-free survival was 0.17. So a really meaningful benefit in preventing and delaying recurrence. We still are waiting on further analysis for overall survival. At this point, there have been three deaths in the placebo arm and none in the selpercatinib arm. The trial did allow for crossover, so that will have to be taken into account. But at this time, we see an event-free survival benefit that's quite significant and very much in line with the other adjuvant targeted therapy trials of osimertinib in the ADAURA trial and alectinib in the ALINA trial. So at this time, we believe that this is practice changing and, excitingly, can be immediately put into practice since selpercatinib is an approved drug. The other analysis included sites of progression. We found that CNS progression and local progression were all reduced with the use of selpercatinib. We also analyzed adverse events on the trial. We found that, in general, the drug was well tolerated. There were dose modifications that were relatively common, dose holds and dose reductions, most commonly for LFT elevations. There are also other toxicities, hypersensitivity syndrome of fever, rash, and LFT elevations that is typically very, very much only at the beginning of treatment and does resolve on a dose hold, and often the drug can be restarted at the same dose. So given that we found the drug was well tolerated and, as I said, led to this very significant event-free survival benefit, we do think that this is immediately practice changing. The drug is already approved. And so I think that when we head back to work next week, I think this will be a good option for our patients in order to prevent recurrence and hopefully improve survival.