Comparison of clinical outcomes of patients with METDex14 NSCLC treated with first-line capmatinib in the GEOMETRY mono-1 study with those of a cohort of real-world patients

Capmatinib (Tabrecta®) is an orally bioavailable, highly potent and selective MET inhibitor (METi). Data from the GEOMETRY mono-1 study, a non-randomized, phase 2 trial of capmatinib in patients (pts) with MET exon 14 skipping mutation (METΔex14) metastatic NSCLC, demonstrated an objective response rate of 68% in treatment-naïve pts. This retrospective cohort study examined the clinical characteristics, treatment patterns, and clinical outcomes of a cohort of real-world (RW) pts with METΔex14 NSCLC from the Flatiron Health-Foundation Medicine de-identified Clinico-genomic Database. RW progression-free survival (rwPFS) and overall survival (OS) of pts who received first-line chemotherapy and/or immune checkpoint inhibitor therapy in the metastatic setting were compared with RECIST-based PFS and OS of treatment-naive METΔex14 NSCLC pts who received capmatinib in the GEOMETRY mono-1 trial. An inverse odds weighting approach was used as a method of covariate balancing that estimated the Average Treatment effect on the Treated (ATT). Baseline demographics and clinical characteristics are in the table. Median (95% CI) PFS was 12.0 (5.5, 20.7) vs median rwPFS of 6.1 (3.4, 8.1) months for the trial and RW pts, respectively; following ATT weighting, median PFS was 12.0 (5.5, 20.7) vs median rwPFS of 6.2 (3.4, 9.1) months, respectively. Median (95% CI) OS was 20.8 (12.4, not reached [NR]) vs 14.8 (7.7, 26.2) months for the trial and RW pts respectively; following ATT weighting, median OS was 20.8 (12.4, NR) vs 20.0 (7.2, NR) months, respectively. A number of RW pts received METi after progression on first line (n=11, pre-weighting; n=8.8, after ATT-weighting)Table: 1346PReal-world patientsGEOMETRY mono-1 (N = 28)Pre-weighting (N = 41)After ATT-weighting (N = 29.4)Female sex18 (64)19 (46)19.8 (67)Age at treatment start, mean (SD)72.4 (7)74 (8.5)72 (8.2)History of smoking10 (36)26 (63)9.5 (32)HistologySquamous cell carcinoma2 (7)2 (5)2.2 (7)Adenocarcinoma25 (89)38 (93)26.8 (91)Other1(4)1 (2)0.4 (1)Brain metastasis3 (11)10 (24)2.3 (8)ECOG PS at baseline07 (25)9 (22)7.3 (25)121 (75)32 (78)22.1 (75)Index treatment groupPD-L1 monotherapy-6 (15)2.2 (8)PD-L1 + chemotherapy-9 (22)5.5 (19)Platinum-doublet chemotherapy-25 (61)21.6 (73)Single-agent chemotherapy-1 (2)0.1 (0)Trial treatment28 (100)--Results are n (%) unless otherwise stated. Open table in a new tab . Results are n (%) unless otherwise stated. Based on this retrospective RW comparison, capmatinib confers longer PFS vs treatments available as first-line for advanced METΔex14 NSCLC, before and after matching for differences in baseline and clinical characteristics.