The Future of RET Inhibitors in Non-Small Cell Lung and Thyroid Cancer - Episode 10

How BLU-667 Has Changed the Treatment Landscape

Transcript: Jacob Sands, MD: Regarding BLU-667, we see response rates around 60%, demonstrating a sign of CNS [central nervous system] activity, where we’re seeing responses. It has also shown that it’s been a well-tolerated drug with a few people really coming off because of toxicities and manageable toxicity profile.

Again, we see, compared with multikinase inhibitors, this really outperforms them in such a substantial way with a better-tolerated drug, with more responses, durable responses, and a sign of CNS activity for this drug as well. We’re pushing the field beyond the multikinase inhibitors and now talking about 2 highly selective drugs with impressive efficacy and adverse-effect profiles.

Benjamin Besse, MD, PhD: With the data we have so far, it’s quite difficult to compare the efficacy of selpercatinib to BLU-667. We know that for A to S, 68% for the first 1 and 58% for the second 1. But what really matters for these patient is PFS [progression-free survival]. And we don’t have enough material that’s out about the BLU-667 compound to have the PFS of these patients. In terms of efficacy, we can see that the overall tolerance is quite similar, although there might be some differences, maybe a bit more elevation of amineitis with selpercatinib. And a bit more neutropenia and anemia with BLU-667.

I think that the overall risk-benefit ratio of the 2 drugs will be quite similar. It’s always good to have 2 drugs to target RET, because some of the patients might have an experience, with 1 or the other drug, of grade 3 or 4 toxicity, and it’s good to have a second drug to switch.

Alexander Drilon, MD: Because we’ve seen impressive results from the ARROW trial of pralsetinib or BLU-667 in RET-dependent cancers, I think the approval of this drug—either for thyroid lung cancers or hopefully a tumor-agnostic approval—can be achieved for any of the selective RET inhibitors. I think this would really change the game in terms of giving clinicians a new option for these patients that’s very active and that’s very safe. That hopefully can be used in the first-line setting to treat these patients as it achieves very impressive outcomes, as we’ve discussed.

Marcia Brose, MD, PhD: If approved, BLU-667 would change the treatment landscape in that having an agent that’s very specifically targeting RET with great response rates—doubling what had previously been seen in vandetanib and cabozantinib, with really good tolerable toxicity profiles. I would definitely be using that. Most people will be using that in the first-line setting and no longer waiting for cabozantinib or vandetanib, and those agents will probably fall to second and third line.

Transcript Edited for Clarity