Effectiveness of standard treatments in non-small-cell lung cancer with METexon14 skipping mutation: a real-world study
Creators: name: Furqan, Muhammad
name: Karanth, Siddharth
name: Goyal, Ravi K
name: Cai, Beilei
name: Rombi, Julien
name: Davis, Keith L
name: Caro, Nydia
name: Saliba, Teddy
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Medicine
subject: Immunology
subject: FOS: Clinical medicine
subject: Cancer
subject: Science Policy

description: <b>Aim:</b> To assess real-world clinical outcomes with standard therapies for advanced non-small-cell lung cancer (aNSCLC) with METexon14 skipping mutation (METex14). <b>Methods:</b> In an oncologists-led retrospective review of medical records, data were abstracted and analyzed for patients initiating first-line (1L) systemic therapy after 1 January 2017. <b>Results:</b> In total 287 aNSCLC patients with METex14, the real-world best overall response rate was 73.4% for capmatinib (n = 146), 68.8% for immunotherapy (IO) monotherapy (n = 48), 52.0% for chemotherapy (CT, n = 30), and 54.8% for IO + CT (n = 63). As compared with capmatinib, patients receiving IO (hazard ratio [HR]: 1.57; 95% CI: 0.77–3.20; p = 0.220), CT (HR: 2.41; 95% CI: 1.19–4.85; p = 0.014) and IO + CT (HR: 2.33; 95% CI: 1.35–4.04; p = 0.003) had higher rates of progression. Further, patients receiving CT (HR: 4.43; 95% CI: 1.54–12.75; p = 0.006) and IO + CT (HR: 3.53, 95% CI: 1.41-8.85; p = 0.007) had higher rates of mortality than patients receiving capmatinib. <b>Conclusion:</b> The study showed better clinical outcomes with capmatinib than other standard therapies in 1L setting for aNSCLC harboring METex14. <b>Real-world study that investigated the outcomes of different therapies used to treat non-small-cell lung cancer patients with mesenchymal-epithelial transition exon 14 skipping mutation</b> A real-world study that investigated clinical outcomes in patients with diagnosis of advanced non-small-cell lung cancer (aNSCLC) with mesenchymal-epithelial transition exon 14 (METex14) skipping–a rare form of genetic mutation–who received treatment with one of the commonly used therapies for this disease: immunotherapy, chemotherapy, immunotherapy + chemotherapy combination and capmatinib, which is a highly selective inhibitor of MET tyrosine kinase protein involved in the growth of cancer cells. The study showed that, in general, patients treated with capmatinib as the frontline therapy more frequently achieved a clinical response in the form of complete tumor resolution or tumor shrinkage, had a lower risk of disease worsening and lived longer than patients who were treated with immunotherapy, chemotherapy or immunotherapy + chemotherapy combination. This study suggests that capmatinib is effective in treating patients with aNSCLC with METex14 skipping who have not been treated with another anticancer therapy previously. It provides evidence to support the use of capmatinib in the frontline setting and may inform clinical decision-making in routine practice. This real-world study of clinical outcomes showed capmatinib to be effective in first-line treatment of patients with advanced/metastatic NSCLC with MET exon 14 skipping mutation. Capmatinib, a tyrosine kinase inhibitor, was the first targeted therapy approved by the US FDA for METex14 patients with advanced non-small-cell lung cancer (aNSCLC). Capmatinib has shown significant efficacy in clinical studies; however, data on capmatinib activity in comparison with other standard therapies when treating patients with aNSCLC harboring METex14, particularly from the real-world settings, are limited. This study conducted a medical record review to assess real-world clinical outcomes of patients with METex14 in aNSCLC treated with capmatinib, or immunotherapy (IO) and/or chemotherapy (CT) at various sites in the USA. Study reviewed 287 patient charts, of whom 146 patients received capmatinib, 48 received IO monotherapy, 30 received CT and 63 received IO + CT as their first-line (1L) for aNSCLC. The study population was approximately 71% male; 49.1% were Non-Hispanic White, with a median duration of follow-up of 11 months from aNSCLC diagnosis and 10 months from the 1L therapy initiation, and most patients (63.1%) had stage IV NSCLC at 1L therapy initiation. Capmatinib in aNSCLC with MET exon 14 had higher real-world overall response rate (73.4% [95% CI: 65.2–80.5%]) and longer time to treatment discontinuation (median- 19.1 months [95% CI: 12.4–not estimable (NE)]), real-world progression-free survival (Median–NE) and overall survival (Median–NE) compared with other standard of care therapies. Multivariable cox regression models indicated that after controlling for demographic and clinical characteristics, 1L CT and IO + CT versus capmatinib had significantly higher rates of treatment discontinuation, progression and mortality. This study provides evidence to support the use of capmatinib in 1L treatment of patients with aNSCLC/mNSCLC with MET exon 14 skipping mutation.