Medicine Matters oncology

At ASCO 2021, I was part of the data sent updating the ARROW trial, which is the phase I/II study of pralsetinib, formerly BLU-667, in patients with RET fusion-positive non-small-cell lung cancer. At this meeting, we updated the data from ARROW with longer follow-up of almost one and a half years.

And what we see there are consistent with the initial data. This is a highly effective drug. In 216 patients, so a sizable data set, we saw a response rate of 69%, a disease control rate of 92%, and a median duration of response of 22 months. These remarkable numbers were even better in the frontline setting, where the initial response rate was 74%.

Important to remember that as the study was first written, these were only patients ineligible for chemotherapy. And as the study evolved, an amendment allowed patients who were eligible for chemotherapy to receive pralsetinib in the first line setting. If we look at those patients in the true frontline setting, the response rate was an astonishing 88% with disease control rate of 96%, a median duration of response that has not yet been reached.

These are remarkable numbers supporting the accelerated approval of pralsetinib, which was granted by the US FDA December 1, 2020. They support early use of this RET inhibitor. Importantly, to use the drug early, you have to identify-- you have to test for RET early. This is not a common biomarker. About 1% of non-small-cell lung cancer will have a RET fusion. But it is important to test, because this is a clear difference maker.

In addition, the drug was very well tolerated. While there are some toxicities, specifically myelosuppression, neutropenia, lymphopenia, largely paper toxicities in my experience, the drug is overall well tolerated. Those respond well to dose reduction. And only 6% of people in the overall safety population stopped pralsetinib due to a treatment related adverse event. This drug currently approved, in my opinion, appropriate for frontline use for RET fusion-positive non-small-cell lung cancer. And we'll continue to follow as these data mature.

So the ARROW study looked at patients with advanced non-small-cell lung cancer, as we've seen from other studies. Notably, the ADAURA trial, the use of targeted therapy in the adjuvant setting after resection significantly prolonged disease free survival. Would we see the same thing in a RET fusion-positive lung cancer? And clearly, there's no data. It will take a long time to generate that data, given the rarity of these events.

In my practice, I would say that it's logical. A similar benefit would be extended. And because the drug is very well tolerated, I do think it'd be a reasonable consideration. But it'll be quite some time before we have actual data supporting that use in practice. Before that, we will probably have neoadjuvant data. And ongoing neoadjuvant effort is looking at RET kinase inhibitors for resectable lung cancer, any perioperative space. So that will lend us some information. For the time being, we'll have to use our clinical judgment.