Advances in Biomarker-Driven Therapy for Advanced NSCLC - Episode 5

The VISION Trial

Briana Contreras

Paul K. Paik, MD

An expert in non-small cell lung cancer discusses the key efficacy and safety findings from the VISION trial of tepotinib in patients with NSCLC and MET exon 14 skipping alterations.

Briana Contreras: Can you share the design of the VISION study, and what kind of patients were included?

Paul K. Paik, MD: The VISION trial was a straightforward phase 2 study of the drug tepotinib given to patients with non–small cell lung cancer. There was randomization, so everyone got the drug, and the primary end point of this was overall response rate. We really wanted to see if there was a good tumor-shrinking signal present in our patients, and this was defined by an independent review committee. There were secondary end points also for investigator-assessed response rates, PFS [progression-free survival], duration of response—the standard things we look for. In terms of eligibility, patients with any kind of non–small cell lung cancer were allowed to participate. This included patients with squamous cell lung cancers; patients with sarcomatoid carcinomas were included also. Patients with asymptomatic brain metastases were also allowed. Patients who had received treatment with brain metastases that were no longer issues were also allowed onto the study.

Briana Contreras: What were the findings on the key efficacy end point?

Paul K. Paik, MD: The findings regarding the key efficacy end point, which was overall response rate, was that for the total cohort the overall response rate was about 46% to 47%, with a median progression-free survival duration—which was the secondary end point—of about 9 months. The VISION study also purposefully looked at the detection of MET exon 14 skipping in liquid biopsies in the blood to see whether that was a predictive biomarker. The study also had, as part of it, a prespecified analysis of patients in terms of the primary end points and secondary end points who had MET exon 14 skipping identified in the tissue and then MET exon 14 skipping identified in the liquid biopsy. Here, an important point that we found was that there were similar efficacy signals in both populations—patients who had exon 14 skipping detected in the blood as well as [those who had it] in the tumor—and there was also consistency in the efficacy across all lines of therapy. Whether you gave tepotinib in the up-front setting or later on, after the standard first-line setting—for example, therapy—the efficacy was similar.

Briana Contreras: What were the key safety findings?

Paul K. Paik, MD: The safety findings for tepotinib were similar to safety findings for other MET inhibitors. There’s a fingerprint that emerges for adverse effects when MET inhibition is delivered to patients. That fingerprint has to do with things like peripheral edema; the rate of peripheral edema that happened to patients with any grade was about 60% in the VISION study, and we have seen similarly high rates of edema with other selective MET inhibitors, like savolitinib and capmatinib. There were other adverse effects that we saw that were associated with MET inhibition, particularly increased creatinine, for example, which we think has to do, in most instances, with the way creatinine is filtered and excreted at the kidney—there’s not really intrinsic damage to the kidney. We saw the development of benign pleural effusions in response to tepotinib, and that’s related to the edema phenomenon, so these infusions can develop that aren’t because of cancer progressions. That’s important to know for the treating oncologist: When you see these, you really need to test to make sure they’re malignant and not benign as an adverse effect for a drug, and that you don’t stop it prematurely. We saw some other adverse effects that we often see: increases in liver transaminases, which really amounted to not much clinically, and then very low rates of pneumonitis, as we see with other drugs.

Transcript edited for clarity.