Background
c-Met (MET) protein overexpression (OE) is associated with poor prognosis in non-small cell lung cancer (NSCLC) and is being investigated as a therapeutic target and predictive biomarker.
This ongoing, retrospective, US real-world study assesses c-Met OE by immunohistochemistry (IHC) on archived tissue samples from patients (N=500) with metastatic nonsquamous NSCLC at Caris Life Sciences™ and links patient data to the ConcertAI Real-World Data 360™ (RWD360) database. Patients who had archived tissue samples from up to 24 months prior to study initiation were included. Results are reported as c-Met protein OE positive (≥25% tumor cells at 3+ intensity) and high c-Met protein OE (≥50% at 3+) relative to low/no c-Met protein OE (<25% tumor cells or at <3 intensity). Concurrence of c-Met OE with MET amplification (METAmp), METex14 skipping mutations, and PD-L1 positivity (≥50% staining by IHC) is presented. We report results from an interim analysis (IA).
Of 148 eligible patients, 31 (20.9%) were c-Met protein OE positive. Samples were collected primarily at time of diagnosis, while median archived sample age at MET IHC assessment was 18 months. A total of 144 patients were linkable with RWD360 and included in the IA (29 c-Met OE positive; 115 c-Met OE negative). Median follow-up from first line (1L) start (c-Met OE positive, c-Met OE negative) was 255 and 236 days; median age at 1L start was 71 and 70 years. Among patients assessed for biomarker overlap, the positivity rates (c-Met OE positive [n=31], c-Met OE negative [n=115]) were: METAmp, 3.2% (95% CI: 0.1%–16.7%) and 0.9 % (P=0.38); METEx14 skipping, 12.9% (95% CI: 3.6%–29.8%) and 2.6% (P=0.04); PD-L1 ≥50%, 58.1% (95% CI: 39.1%–75.5%) and 20.9% (P≤0.01). When examining overall survival from 1L therapy start, a greater proportion of patients with high c-Met OE (8/13, 61.5%) had a death event compared with patients with c-Met negative OE (29/75, 38.7%), suggesting negative prognostic value of c-Met protein OE.
The IA outcomes are consistent with high prevalence of c-Met OE relative to other MET aberrations. Completed analysis of the entire cohort (N=500) will characterize the potential negative prognostic value of c-Met OE with longer follow-up.