1254P Efficacy and safety of tepotinib in patients (pts) with advanced age: VISION subgroup analysis of pts with MET exon 14 (METex14) skipping NSCLC

Abstract

The pt population defined by METex14 skipping is typically elderly, and may be challenging to treat due to comorbidities. In the VISION study (median age 73.1 years [yr; range 41–94]), the selective MET inhibitor tepotinib had an objective response rate of 44.7%, and median duration of response of 11.1 months. We investigated outcomes according to age. Pts with advanced METex14 skipping NSCLC received 500 mg (450 mg active moiety) tepotinib orally once daily. All pts who received tepotinib in Cohorts A (primary analysis) and C (confirmatory) were assessed for safety; pts in Cohort A were assessed for efficacy. Primary endpoint was objective response by independent review committee. Secondary endpoints included duration of response, and safety. Subgroup analysis according to age was predefined. A total of 152 pts were enrolled in Cohort A. Baseline characteristics were similar in pts <75/≥75 yr (n=84/68): 52.4/51.5% were male, 60.7/41.2% had a history of smoking, 70.2/76.5% had ECOG PS 1, 89.3/82.4% had adenocarcinoma histology, and 44.0/47.1% were treatment-naïve. Efficacy in pts <75 or ≥75 yr is shown (Table). Of 124 patients who discontinued tepotinib, 47 received subsequent treatments; the majority were <75 yr (n=36; 76.6%). A total of 255 pts were assessed for safety. In pts <75/≥75 yr (n=146/109), treatment-related adverse events (TRAEs) occurred in 87.7/84.4%, Grade ≥3 TRAEs occurred in 18.5/33.9%, and TRAEs led to discontinuation in 7.5/14.7%. The most common TRAE, peripheral edema, occurred in 56.2% of pts <75, and 51.4% of pts ≥75 yr.Table: 1254PEfficacy (IRC)Patients <75 years (n=84)Patients ≥75 years (n=68)Best objective response, n (%)Complete response00Partial response41 (48.8)27 (39.7)Stable disease19 (22.6)20 (29.4)Progressive disease17 (20.2)9 (13.2)Not evaluable7 (8.3)12 (17.6)Objective response rate,48.839.7% (95% CI)(37.7, 60.0)(28.0, 52.3)Disease control rate,71.469.1% (95% CI)(60.5, 80.8)(56.7, 79.8)Median duration of response,12.410.1months (95% CI)(8.4, not estimable)(5.8, 18.5)Median progression-free survival,10.38.6months (95% CI)(8.2, 12.1)(6.9, 12.4)Data cut-off: July 1, 2020.CI, confidence interval; IRC, independent review committee. Open table in a new tab Data cut-off: July 1, 2020. CI, confidence interval; IRC, independent review committee. Tepotinib demonstrated robust and durable efficacy in elderly pts, with a manageable safety profile, and a low proportion of TRAEs leading to discontinuation. Given the vulnerability of pts of advanced age, prioritization of effective and convenient targeted therapies in this population is warranted.