An Adjusted Treatment Comparison Comparing Amivantamab Versus Real-World Clinical Practice in Europe and the United States for Patients with Advanced Non-Small Cell Lung Cancer with Activating Epidermal Growth Factor Receptor Exon 20 Insertion Mutations

Abstract

Introduction: Patients with advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC) with Exon 20 insertion mutations (Exon20ins) have poor prognoses, exacerbated by a previous lack of specific treatment guidelines and unmet need for targeted therapies. Amivantamab, an EGFR and MET bispecific antibody, demonstrated efficacy and tolerability in patients with advanced EGFR-mutated NSCLC with Exon20ins following platinum-based therapy in CHRYSALIS (NCT02609776; Cohort D+). Since CHRYSALIS was single-arm, individual patient data (IPD)-based adjusted analyses versus similar patients in real-world clinical practice (RWCP) were conducted to generate comparative evidence.

Methods: RWCP cohorts were derived from seven European and US real-world sources, comprising patients fulfilling CHRYSALIS Cohort D+ eligibility criteria. Amivantamab was compared with a basket of RWCP treatments. Differences in prognostic characteristics were adjusted for using inverse probability weighting (IPW; average treatment effect among the treated [ATT]). Balance between cohorts was assessed using standardized mean differences (SMDs). Overall response rate (ORR; investigator- [INV] and independent review committee-assessed [IRC]), overall survival (OS), progression-free survival (PFS; INV and IRC) and time-to-next treatment (TTNT) were compared. Binary and time-to-event endpoints were analyzed using weighted logistic regression and proportional hazards regression, respectively.

Results: Pre-adjustment, baseline characteristics were comparable between cohorts. IPW ATT-adjustment improved comparability, giving closely matched characteristics. ORR (INV) was 36.8% for amivantamab versus 17.0% for the adjusted EU + US cohort (response rate ratio [RR]: 2.16). Median OS, PFS (INV) and TTNT were 22.77 versus 12.52 months (hazard ratio [HR]: 0.47; p < 0.0001), 6.93 versus 4.17 months (HR: 0.55; p < 0.0001) and 12.42 versus 5.36 months (HR: 0.44; p < 0.0001) for amivantamab versus the adjusted EU + US cohort, respectively. Results were consistent versus EU- and US-only cohorts, and when using IRC assessment.

Conclusion: Adjusted comparisons demonstrated significantly improved outcomes for amivantamab versus RWCP, highlighting the value of amivantamab in addressing unmet need in patients with advanced EGFR Exon20ins NSCLC following platinum-based therapy.

Trial registration: CHRYSALIS: NCT02609776.

Keywords: Adjusted comparison; Amivantamab; Exon 20 insertion mutations; Non-small cell lung cancer; Real-world clinical practice.

Fig. 1

Kaplan–Meier curve for OS for CHRYSALIS versus EU + US cohort (amivantamab vs. unadjusted and adjusted RWCP). ATT average treatment effect among the treated, HR hazard ratio, IPW inverse probability weighting, OS overall survival, RWCP real-word clinical practice

Fig. 2

Kaplan–Meier curve for PFS (INV) for CHRYSALIS versus EU + US cohort (amivantamab vs. unadjusted and adjusted RWCP). ATT average treatment effect among the treated HR: hazard ratio, INV investigator-assessed, IPW inverse probability weighting, PFS progression-free survival, RWCP real-word clinical practice

Fig. 3

Kaplan–Meier curve for TTNT for CHRYSALIS versus EU + US cohort (amivantamab vs. unadjusted and adjusted RWCP). ATT average treatment effect among the treated, HR hazard ratio, IPW inverse probability weighting, RWCP real-word clinical practice, TTNT time-to-next treatment