Comparative Effectiveness of Mobocertinib and Standard of Care in Patients with NSCLC with EGFR Exon 20 Insertion Mutations: An Indirect Comparison
Cette étude compare les données d'un essai de phase I/II évaluant l'efficacité du mobocertinib et les données américaines de vie réelle évaluant l'efficacité des traitements standard chez des patients atteints d'un cancer du poumon non à petites cellules présentant des mutations de l'EGFR par insertion de l'exon 20
Introduction: Mobocertinib is a novel, first-in-class, irreversible, oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) designed to selectively target in-frame EGFR exon 20 insertions (ex20ins). Comparative effectiveness data for mobocertinib versus real-world treatments are lacking in this rare population. This study compared data for mobocertinib reported in a Phase I/II single-arm clinical trial with an external control group consisting of patients who received available treatment in the real-world setting in the United States (US). Materials and Methods: The mobocertinib group included platinum-pretreated patients with advanced EGFR ex20ins non-small cell lung cancer (NSCLC) receiving mobocertinib 160 mg QD in an ongoing, single-arm, phase 1/2 clinical trial (NCT02716116; n=114). The real-world data (RWD) group included platinum-pretreated patients with advanced EGFR ex20ins-mutant NSCLC from the Flatiron Health database (n=50). Inverse probability treatment weighting based on the propensity score method controlled for potential confounding between groups. Confirmed overall response rate (cORR), progression-free survival (PFS), and overall survival (OS) were compared between groups. Results: After weighting, baseline characteristics were balanced. Patients in the RWD group received EGFR TKI (20%), immuno-oncology therapy (40%), or any regimens containing chemotherapy (40%) in the second- or later-line setting. In the mobocertinib and RWD groups, respectively, cORR was 35.1% and 11.9% (odds ratio: 3.75 [95% confidence interval (CI): 2.05, 6.89]); median PFS was 7.3 and 3.3 months (hazard ratio: 0.57 [95% CI: 0.36, 0.90]); and median OS was 24.0 and 12.4 months (hazard ratio: 0.53 [95% CI: 0.33, 0.83]) after weighting. Discussion: Mobocertinib showed substantially improved outcomes versus an external control group using available therapies in platinum-pretreated patients with EGFR ex20ins-mutant NSCLC. In the absence of comparative evidence from randomized trials, these findings help elucidate potential benefits of mobocertinib in this rare population.