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.

8645 Background: Metastatic non-small cell lung cancer (mNSCLC) remains a leading cause of cancer-related deaths, with MET exon 14 skipping mutations (METex14) identified as a key oncogenic driver in 1%–4% of cases. MET tyrosine kinase inhibitors (TKI) such as capmatinib and tepotinib have demonstrated efficacy in clinical trials, leading to FDA approval in any treatment line. This study aims to compare first-line (1L) survival outcomes with MET TKI versus immune checkpoint inhibitors ± chemotherapy (IO ± Chemo). Methods: 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. Results: 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). Conclusions: 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.