Asians with MET exon 14 skipping NSCLC achieve durable response with tepotinib

The MET inhibitor tepotinib demonstrates clinically meaningful antitumour activity, with durable efficacy and manageable safety profile in Asian nonsmall cell lung cancer (NSCLC) patients with MET mutations associated with exon 14 skipping, as shown in the subset analysis of the single-arm, phase II VISION study.

Among the 106 Asian patients enrolled in VISION, the objective response rate (ORR) was 57.5 percent (95 percent confidence interval [CI], 47.6–67.1), with a median duration of response (DOR) of 18.5 months (95 percent CI, 10.4–not estimable), reported Dr James Yang from the National Taiwan University Cancer Center, Taipei City, Taiwan.

MET exon 14 skipping mutations were detected by tissue biopsy in most patients (78 percent) and by both tissue and liquid biopsies in 25 patients (24 percent), Yang said at ESMO Asia Congress 2022. But whether the mutations were detected by liquid or tissue biopsy, the response rate was consistent (60.2 percent in the tissue group and 58.3 percent in the liquid group, respectively).

Moreover, factors such as age, sex, smoking history, histology (adenocarcinoma vs squamous), ECOG PS, brain metastases, and line of therapy did not influence response with tepotinib, he added.

For other efficacy outcomes in the overall Asian cohort, the median disease control rate (DCR) was 80.2 percent (95 percent CI, 71.3–87.3), median progression-free survival was (PFS) was 13.8 months (95 percent CI, 9.6–19.9), and median overall survival (OS) was 23.7 months (95 percent CI, 19.3–not estimable). [ESMO Asia Congress 2022, abstract 321MO]

Yang noted small differences between the tissue- and liquid-biopsy detection groups. For example, patients with mutations detected by liquid biopsy had a slightly lower DCR (72.9 percent vs 84.3 percent), longer median DOR (18.5 vs 13.4 months), and shorter median PFS (11.0 vs 14.7 months) and OS (19.9 vs 26.8 months).

Among the 50 patients (47.2 percent) who received tepotinib in the first-line setting, the drug also showed robust and durable effects. The ORR was 66.0 percent, median PFS was 14.8 months, and median DOR and OS were not reached.

In terms of safety, the patients were able to stay on tepotinib with dose modifications and interruptions, according to Yang.

Treatment-related adverse events (TRAEs) occurred in the vast majority (95.3 percent) of patients, with 38.7 percent having grade ≥3 events. TRAEs led to dose reduction in 30.2 percent of patients, dose interruption in 47.2 percent, and permanent discontinuation in 13.2 percent; none resulted in death. Most common TRAEs were peripheral oedema (65.1 percent), creatinine elevation (42.5 percent), and hypoalbuminaemia (40.6 percent).

The Asian subset of VISION included 38 patients from Japan, 20 from South Korea, 12 from Taiwan, 30 from China, and six outside Asia. Their median age was 70.5 years, and 39.6 percent were women. A total of 43.4 percent patients had smoking history, 79.2 percent had adenocarcinoma, and 73.6 percent had ECOG PS 1. All patients received tepotinib at 500 mg (450 mg active moiety) once daily.

The findings in this Asian subset echo that in the overall VISION population, Yang said, adding that the overall data support the use of tepotinib in first or subsequent lines of therapy for Asian NSCLC patients with MET exon 14 skipping mutations.