Real-world effectiveness of MET inhibitors versus immunotherapy ± chemotherapy in 1L for patients with MET exon 14 skipping mutations in non-small cell lung cancer

Patient characteristics and survival outcomes were retrospectively analyzed for METex14 mNSCLC patients who received 1L therapy with either (1) MET TKI (tepotinib and capmatinib) or (2) IO ± Chemo. Patients were excluded if they had EGFR alterations. Data were sourced from ConcertAI's Patient360 and RWD360, datasets sourced from oncology EHR in the US.

Among a total of 344 patients, 174 (50.6%) were > 80 years of age, 94 (87.9%) had non-squamous mNSCLC, 176 (51.2%) were female, and 71 (20.6%) had ECOG PS ≥2. As 1L, 202 received MET TKI, 61 received IO + Chemo, and 81 received IO only. Baseline clinicopathologic features were balanced except for a slightly higher proportion of patients with TPS PD-L1 ≥50 in the IO ± Chemo group (p< 0.05). At a median follow up of 40.7 months (mo), in the overall group median progression-free survival (mPFS) was 6.6 mo (95% CI: 5.8–8.8) and median overall survival (mOS) was 15.5 mo (95% CI: 14.4–18.3). MET TKI yielded a mPFS of 7.8 mo (95% CI: 6.2–9.1) and a mOS of 13.8 mo (95% CI: 11.4–17.6). IO ± Chemo resulted in a mPFS of 5.1 mo (95% CI: 3.7–8.2) and a mOS of 21.9 months (95% CI: 15.5–25.8). The mPFS did not differ significantly between groups (p =0.38), while mOS favored IO ± chemotherapy (p= 0.03). Objective response rate was 61.0% with MET TKI and 50.7% with IO ± Chemo (p= 0.74); disease control rate was significantly higher with MET TKI (77.0% vs 64.8%; p= 0.03). In subgroup analysis, among patients with PD-L1 ≥50, OS was significantly longer with 1L IO ± Chemo compared with MET TKI (22.0 mo, 95% CI: 7.5–34.3 vs. 8.5 mo, 95% CI: 6.6–16.5; p< 0.02). In contrast, among patients with PD-L1 < 50, MET TKI was associated with longer PFS (9.2 mo, 95% CI: 4.2–11.7 vs. 4.9 mo, 95% CI: 2.1–11.0; p= 0.07) although OS was similar (17.6 mo, 95% CI: 9.6–29.6 vs. 14.5 mo, 95% CI: 4.0–23.2; p= 0.57).

Among patients with METex14 mNSCLC, those treated with 1L IO ± Chemo had a better OS compared to those treated with MET TKI. This seems especially valid for patients with PD-L1 ≥50, for whom IO ± Chemo significantly improved OS. However, patients with PD-L1 < 50 showed prolonged PFS when treated with MET TKI. This highlights the need for personalized treatment patterns in this patient population.