Hello, my name is Tejas Patil. I'm a thoracic oncologist at the University of Colorado Cancer Center, and there were a lot of exciting abstracts in oncogene-driven non-small-cell lung cancer at the ASCO 2020.
For the ALK rearranged non-small-cell lung cancer abstracts, there were two that I found interesting to cover. One was the abstract 9518, which I won't cover in great depth other than to say this was an abstract looking at the overall survival results-- five-year overall survival results from alectinib versus crizotinib. And not surprisingly, there was a survival benefit for alectinib, which was 62.5% versus 45.3%.
Plasma samples were taken in patients before enrollment in the trial. So there was 136 from the brigatinib arm and 127 from the crizotinib arm. And they were able to detect the EML ALK4 mutation in plasma to be eligible for the study.
There were three ALK variants that were detected in the plasma, so strain one, two, and three. What was interesting about this study was that variant one was more frequently associated with brain metastases and that variant three had a poor progression-free survival relative to variant one and variant two.
Now, it needs to be said that brigatinib was better than crizotinib for all variants. But when you look within each group, these trends of variant one having more brain metastases and variant three having a poorer progression-free survival held true.
Interestingly, they also looked at TP53 and showed that there's emerging evidence that it's a negative prognostic marker. This has been shown in other tumor subtypes such as EGFR and ROS1.
And so what I thought what was interesting about this study is it highlights the possibility that we may be starting to see certain baseline prognostic markers separate out ALK-positive lung cancer patients into sort of a good ALK group versus a bad ALK group, and understanding these baseline prognostic markers can really help develop more customizable treatments.
The next abstracts I'm going to cover for ASCO 2020 involve the RET oncogenes. This has been a very exciting subgroup given that there are two novel agents-- novel tyrosine kinase inhibitors in this space that have previously never been available for this patient population.
The first abstract I'm going to cover is 9515. This is an abstract looking at pralsetinib, which is the BLU-667 study. Here, the patient population was 116 patients, and it's the study that found that there was an objective response rate of 65%. The duration of response was not reached at this study. And the principal adverse events were elevated AST/ALT elevations, anemia, and hypertension.
And then I'm going to quickly also contrast this with abstract 9615, which is a LOXO study. Now this abstract should be mentioned as a little bit different in that they were very much looking at intracranial efficacy of their drug. So they enrolled 79 patients with RET-positive disease. And what was really impressive was that in the 14 patients that had evaluable disease, it was 93% objective intracranial response rate with an intracranial duration of response of 10.1 months. The adverse events were not reported in this study, but if you look at the same company's product in a different trial, they had very similar adverse events such as elevated AST, ALT, anemia, and hypertension.
And my thoughts when I kind of look at these two products together is that for the BLU-666 study, the interesting fact there was that the objective response rate was similar regardless of which RET fusion partner was looked at. So I thought that was kind of interesting, and that will be an emerging topic moving forward.
For the LOXO trial, what was really impressive is that there's clear intracranial efficacy with this tyrosine kinase inhibitor. It should be mentioned that the BLU-667 study also mentioned intracranial efficacy, but I'll wait to see dedicated intracranial objective response rates in the future.
And finally, I think an important aspect of managing these patients moving forward is really starting to understand mechanisms of resistance. So as these drugs get licensed, it'll be very important moving forward to understand exactly how RET non-small-cell lung cancer adapts to these tyrosine kinase inhibitors and what kind of unique resistance mutations emerge.
The next set of abstracts that I would like to discuss are abstracts related to MET alterations in non-small-cell lung cancer. This has been a very exciting space, and there's been several novel agents introduced that specifically target the MET pathway.
The first abstract, 9519, is a study of capmatinib in MET-amplified patients. This is specifically looking at cohort six from the geometry study. In this, there's a patient population included, MET-amplified patients. And here, that definition of MET-amplification was a gene copy number greater than 10 in patients who were pretreated with one to two lines of therapy.
And what you'll see here is that the response rate to capmatinib in this group in the first line setting was 40%, and in the second line or greater study it was 29%. Similarly, the duration of response was 8.3 months in the first line-- this was within 20 patients that were included for this-- and 7.54 months in the second line. Similarly, PFS was four months in the first line and about 4.17 months in the second line or greater.
So my thoughts on this abstract was that this is an exciting intervention for patients with MET gene amplification. I think an evolving target is that the definition of gene amplification is very tricky, and there are multiple ways of defining it. So you can define it by gene copy number, or you can define it by the ratio of the MET gene to chromosome 7. And I don't think there's a universal consensus on what's the most optimal cutoff for MET gene application. And I think because of that lack of consensus, we're going to see, depending on where you put the cutoff, different outcomes from different clinical trials based on the selection criteria that they use.
Nonetheless, the important takeaway from this trial also is that we see a lot of peripheral edema and nausea, and that's very common with MET inhibitors. And we'll see that in a subsequent abstract that I cover.
Next I'm going to cover abstract 9556. This is looking at primary efficacy for tepotinib. This is in the VISION trial. And here, the patient population is MET exon 14 skipping mutations. This trial enrolled 151 patients. They collected both tissue and plasma-circulating tumor DNA. And in this trial, they separated out the responses based on whether they obtained liquid biopsies versus tissue biopsies.
For the response rate, it was 44% in the patients that had liquid biopsies. That is to say they had MET exon 14 detected via circulating tumor DNA blood. And it was 47% for patients that had tissue biopsies.
The duration of response was approximately the same for both groups. So it was 11.1 months in the liquid-biopsy group and 12.4 months in the tissue-biopsy group. Similarly, the PFS was similar, 8.5 months in the liquid-biopsy groups relative to 11 months in the tissue group.
In this abstract, they also reported immature overall survival data-- so 19.1 months with tepotinib. In addition, they reported intracranial objective response rate of 55% with an intracranial progression-free survival of 10.9 months. I would like to highlight that the emergent treatment-related adverse effects were peripheral edema seen in about 63% of patients with an 11% discontinuation rate.
So my thoughts for this study is that tepotinib is also an exciting novel MET inhibitor. There's demonstration of intracranial objective response rate, which is very encouraging given that the only MET inhibitor that is available currently is crizotinib, which has limited intracranial coverage. I think peripheral edema is going to be a major concern for both capmatinib and tepotinib, and they'll need to be strategies to think about how to make these manageable as various doses are brought into the clinic.