OBJECTIVES: To assess the relative efficacy and safety of amivantamab vs. mobocertinib in patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (Exon20ins) mutations by conducting unanchored matching-adjusted indirect comparisons (MAIC) using patient-level data from CHRYSALIS and aggregate data from the mobocertinib trial NCT02716116.

METHODS: Inclusion/exclusion criteria and outcome definitions were broadly similar in both trials. The CHRYSALIS primary efficacy (n=81; median follow-up=14.5 months) and safety (153; 9.9 months) populations were compared with mobocertinib in the Platinum Pretreated Patients cohort (114; 14.2 months). Populations were matched on prior therapies, ECOG, histology, brain metastases, age, race, gender and smoking history. Weighted Cox and logistic regression models were used to estimate relative efficacy of time-to-event (HR for progression-free survival [PFS IRC], overall survival [OS]) and binary (reported as relative response rates (RRR) for overall response [ORR IRC], and relative risk (RR) for adverse events [AE]) endpoints.

RESULTS: MAIC estimates of relative efficacy for amivantamab vs. mobocertinib were: PFS: HR=1.09 [95%CI: 0.69, 1.71]; OS: HR=0.70 [0.39, 1.24]); ORR: RRR=1.73 [0.84, 3.58]. 15 of 23 all-grade treatment-related AE reported for mobocertinib occurred significantly less with amivantamab, with largest differences for diarrhea (RR=0.12 [0.07,0.23]), decreased appetite (0.23 [0.11,0.49]), nausea (0.52 [0.31,0.88]), vomiting (0.24 [0.11,0.52]), dry skin (0.42 [0.42,0.73]), increased levels of creatinine (0.02 [0.00,0.12]), lipase (0.04 [0.01,0.30]) and amylase (0.04 [0.01,0.32]). Dermatitis (2.55 [1.64,3.97]) and increased ALT (2.24 [1.05,4.77]) occurred significantly more with amivantamab. Grade 3+ treatment-related, treatment-emergent, and serious AEs were significantly less frequent with amivantamab: RR=0.44 [0.16;0.54], 0.72 [0.25;0.91], and 0.61 [0.42;0.91], respectively. Sensitivity analyses from different datacuts with different duration of follow-up showed consistent results.

CONCLUSIONS: The MAIC suggests that amivantamab has similar efficacy and more favorable safety profile in comparison with mobocertinib in EGFR Exon20ins NSCLC.