36P Indirect comparison of mobocertinib trial data vs real-world data in patients with EGFR exon 20 insertion (ex20ins)+ non-small cell lung cancer (NSCLC)

Abstract

Mobocertinib received accelerated approval by the US FDA for the treatment of adult patients (pts) with locally advanced or metastatic NSCLC with EGFR ex20ins with disease progression on or after platinum-based chemotherapy (platinum), based on the results of a phase I/II single arm trial (NCT02716116). This study indirectly compared overall survival (OS), progression-free survival (PFS), and confirmed overall response rate (cORR) for the mobocertinib trial with real-world data (RWD). Clinical outcomes were compared in platinum-pretreated pts with EGFR ex20ins+ NSCLC treated with mobocertinib 160 mg QD in the second or later line in NCT02716116 (cut-off Nov 2020) vs. real-world treatment from a chart review study in Germany (RWD). RWD included platinum-pretreated pts with Eastern Cooperative Oncology Group (ECOG) 0-1 and no other malignancy in the prior 3 years. Inverse probability of treatment weighting method was used to adjust for group differences in key baseline variables, including age, sex, ECOG, smoking status, brain metastasis, time from advanced diagnosis, and histology. This study included 157 platinum-pretreated pts (n=114 mobocertinib/n=43 RWD; mean age: 60/60 years; male: 34%/21%; brain metastases: 35%/30%; median prior lines; 2/1). RWD platinum-pretreated pts received EGFR tyrosine kinase inhibitor (37%), chemotherapy (mono 26%, doublet 9%), and immunotherapy alone (19%) or combined with doublet chemotherapy (9%). Most baseline variables were balanced after weighting. For mobocertinib vs weighted RWD, cORR was 35% vs 0%, median PFS was 7.3 vs 2.5 months, and median OS was 24.0 vs 9.8 months (Table).Table: 36POutcomeMobocertinib (n = 114)RWDHazard Ratio (95% CI)Unweighted (n = 43)Weighted (n=109)UnweightedWeightedccORR, % (95% CI)35.1a (26.4, 44.6)0%b0%bMedian PFS, mo (95% CI) Log-rank p-value7.3a (5.6, 8.8)3.0 (2.0, 4.4)2.5 (1.5, 3.4)0.33 (0.22, 0.50) <0.0010.28 (0.17, 0.46) <0.001Median OS, mo (95% CI) Log-rank p-value24.0 (14.6, 28.8)11.3 (8.9, 14.5)9.8 (4.3, 13.3)0.49 (0.31, 0.77) 0.0030.48 (0.27, 0.86) 0.018a cORR and PFS: per investigator’s assessment using RECIST 1.1 b Tumor response was evaluated by review of radiologic images based on RECIST v1.1. c Inverse probability of treatment weighting with regression adjustment for time from advanced diagnosis. CI, confidence interval Open table in a new tab a cORR and PFS: per investigator’s assessment using RECIST 1.1 b Tumor response was evaluated by review of radiologic images based on RECIST v1.1. c Inverse probability of treatment weighting with regression adjustment for time from advanced diagnosis. CI, confidence interval Among platinum-pretreated pts with EGFR ex20ins+ NSCLC, mobocertinib showed significantly higher cORR, and prolonged PFS and OS compared to treatment in the real-world setting, with or without weighting to match baseline variables.