The Future of RET Inhibitors in Non-Small Cell Lung and Thyroid Cancer - Episode 9

ESMO 2019 LIBRETTO-001 Trial Updates

Transcript:Marcia Brose, MD, PhD: At the ESMO [European Society for Medical Oncology] 2019 Annual Meeting, an update of the LIBRETTO-001 study for differentiated thyroid cancer and medullary thyroid cancer was presented, and the partial response was in the upper 50% range, 57% to 59%. That includes a couple of patients who actually had complete responses. And that’s really significant because in the other drugs that we’ve used that are FDA approved, we hadn’t seen any complete responses.

So right off the bat we have something new. One, a very high response rate in the upper 50% range, as opposed to in the 20% or 30%, which were just lower. And in addition to what we have now, what was very exciting is that the progression-free survival curve showed that it still hasn’t been reached and the minimum at this point is at least 11 months. That’s really a very good progression-free survival because these patients in the phase III were really getting at least 11 months on average. To have it be a minimum of 11 months really is saying that the progression-free survival is going to be long, and probably longer than what we’ve seen so far. We’ll have to wait and see what the final is.

Of course, you can’t compare these phase IIs to phase IIIs that have happened before, but these are still very promising results.

As far as the efficacy that was presented at ESMO 2019 for the LOXO-292 study, what we’ve continued to see is primarily grade 1 toxicity and some grade 2. And if you look only at the results for what is considered attributable to the drug, we’re talking almost no grade 2s with less than a couple percent and almost a few grade 1s—a few more, but still this is absolutely remarkable, with no grade 3s whatsoever. The toxicity is considerably better than what we’ve seen before, as well as efficacy that’s also vastly improved over what we’ve seen before.

I think the approval of LOXO-292 and BLU-667, the specific RET inhibitors, will change the landscape. Because when you have agents that are doubly efficacious with a much better toxicity profile, you’re going to want to give those drugs up front. I think for those patients who are eligible, because they either are differentiated thyroid cancer patients, papillary particularly, with a RET fusion, or if they’re medullary with a point mutation for whatever reason—sporadic or hereditary—those are patients I’m going to want to find out about up front; do testing as soon as I know they’re going to need a kinase inhibitor; and if they do have the inhibitor, in my clinic they will be getting these in the first-line setting.

Benjamin Besse, MD, PhD: If I look at the other molecularly selected non—small cell lung cancer [NSCLC], such as the EGFR mutation, as soon as an EGFR inhibitor was approved, the uptake was very quick. Because the difference in term of efficacy of toxicity compared with platinum based, these drugs are very lucky to be prescribed.

As in other molecularly selected in NSCLC such as EGFR and ALK, a selective TKI has been approved. The uptake has been very high because for a patient, it will be much better to have an oral drug with very few toxicities compared to a platinum-based chemotherapy, and the outcome is much better with the selective inhibitor.

Alexander Drilon, MD: The approval of selpercatinib for RET-fusion-positive lung cancer patients would represent a major advancement, especially because to date there’s no approved targeted therapy for these patients, and it would represent the first drug ever approved for this indication. This has a huge impact on the treatment community because these patients make up approximately 1% to 2% of non—small cell lung cancers. Meaning it’s almost the same number of patients who have ROS1-rearranged lung cancers. This would be a very big deal for us.

Transcript Edited for Clarity