Christian Rolfo, MD, PhD, Icahn School of Medicine, Mount Sinai Medical Center, New York, New York, discusses results from the phase 2 VISION trial comparing the use of liquid and tissue biopsies to detect MET exon 14 skipping mutations among patients with advanced non-small cell lung cancer.

Results demonstrated that both liquid and tissue biopsies are effective ways to detect MET exon 14 skipping mutations in this patient population. However, liquid biopsies may be better in identifying patients with a poorer prognosis and higher tumor load.

Dr Rolfo presented these results at the 2023 ESMO Congress in Madrid, Spain.

Transcript:

Hello, my name is Christian Rolfo, I'm a Professor of Medicine at the Icahn School of Medicine in Mount Sinai and Associate Director for Clinical Research at the Center of Thoracic Oncology in Mount Sinai, New York, [New York]. I had the pleasure to present at ESMO on behalf of co-authors the data on the liquid biopsy and tissue biopsy for identification of the MET exon skipping mutation in advanced non-small cell lung cancer and those are the data coming from the analysis from the phase 2 VISION study on tepotinib.

We know that tepotinib is a highly selective MET inhibitor and is approved as treatment for advanced metastatic MET exon 14 skipping mutation non-small cell lung cancer. The VISION study originally is one of the first studies that enrolled patients based on the detection of oncogenic alterations in liquid and in tissue or in liquid biopsy, and the liquid biopsy were complementary to tissue biopsies to enable the assessment of these alterations. VISION, the trial, showed robust data of durable efficacy of tepotinib in the treatment-naive and previously-treated patients, and this efficacy was also detected for patients who have tissue or liquid biopsy with trends to better time-dependent end points in tissue biopsy-positive patients.

To understand these differences, we evaluated the patients' characteristics and outcomes in the VISION trial according to the MET exon skipping mutation positivity in both tissue and liquid biopsy, as well in circulating tumor DNA burden. In tissue biopsy-positive patients with much baseline liquid-based result, efficacy was analyzed in according also to the liquid biopsy status. We used the assay at the baseline that is the Guardant360. The disposition of the patients was 7,936 patients assessed during the previous screening and we find in these patients 5.9% of them have MET exon 14 skipping mutations in tissue and or liquid biopsy. From 313 patients enrolled, 208 were tissue biopsy-positive and 178 were liquid biopsy-positive. Among the tissue biopsy-positive, 106 of these patients were liquid biopsy-negative and 74 liquid biopsy-positive. The tissue biopsy patients had lower disease burden with lower median sum of the lesion diameters short axis, and fewer patients with the last 3 target or not target lesion—this is important to know because also health-related quality of life baseline was better in tissue versus liquid biopsy-positive patients, so this speaking about the difference in the kind of patients that are positive in liquid biopsy.

The analysis of the tissue-positive patients with matched liquid biopsy results shown to be meaningful during the efficacy of tepotinib in treatment-naive and previously-treated patients, and that is regardless of the liquid biopsy status. Specifically in tissue biopsy-positive patients, there were trends to longer independent end points in patients with negative liquid biopsy results, and in tissue-positive liquid biopsy-negative patients who received first-line tepotinib, the median duration of response was not estimated and the median progression-free survival was around 22.1 months with a median overall survival of 32.7 months.

The analysis according to the baseline circulating tumor DNA burden that was performed at 165 patients with Guardant360 liquid biopsy, we found that it was undetectable in 25 patients and detectable in 140 patients. More of the patients in the detectable than undetectable group have at least 3 target or no target lesion, and the patients with detectable circulating DNA have a shorter progression-free survival and overall survival than those who have the undetectable circulating tumor DNA.

In conclusion, we can say that tepotinib has a robust, durable activity in treatment-naive and previously treated patients, that it was more favorable in MET exon 14 skipping mutation when it was undetectable in the blood, that is confirming the data that we have on ctDNA patients that seems to be doing better in general in outcomes.

The tissue and liquid biopsy are both suitable for complementary approach and that was confirming also the approach that we put together in the IASLC statement paper on liquid biopsy to detect in this case, the MET exon 14 skipping. However, liquid biopsy may select patients with worse prognosis potentially due to the greater disease burden at the baseline—this is very important as we saw in the disposition of the patients. The difference in populations identified by tissue and liquid biopsy should be considered when we interpret the trial data that we are presenting.

Source:

Rolfo C, Obrate Grupp AM, Menzel C, et al. Liquid biopsies (LBx) and tissue biopsies (TBx) for identifying MET exon 14 (METex14) skipping in advanced NSCLC: Analyses from the phase II VISION study of tepotinib. Presented at ESMO Annual Congress; October 20-24, 2023; Madrid, Spain. 1382P