Efficacy of Mobocertinib and Amivantamab in Patients With Advanced Non-Small Cell Lung Cancer With EGFR Exon 20
Sai-Hong Ignatius Ou1, Thibaud Prawitz2, Huamao M Lin3
1Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, CA.
Introduction:
Exon 20 insertions (ex20ins) mutations of the EGFR gene account for 1% to 2% of all non-small-cell lung cancers (NSCLCs). Targeted therapies have been developed to treat this cancer type but have not been studied in head-to-head trials. Our objective was to use a matching-adjusted indirect comparison (MAIC) to assess the efficacy of mobocertinib and amivantamab in patients with NSCLC EGFR ex20ins mutations who were previously treated with platinum-based chemotherapy.
Materials And Methods:
An unanchored MAIC was conducted to estimate the treatment effects of mobocertinib and amivantamab using individual-level data from the mobocertinib phase I/II single-arm trial (NCT02716116) and published data from the amivantamab single-arm CHRYSALIS trial (NCT02609776). Confirmed overall response rate (cORR), progression-free survival (PFS), overall survival (OS), and duration of response (DoR) were assessed.
Results:
Both trials were comparable in terms of study population, study design, and outcome definitions and included 114 patients who received mobocertinib and 114 patients who received amivantamab. After MAIC weighting, all reported baseline characteristics were balanced between mobocertinib and amivantamab. The weighted odds ratio (OR) [95% confidence interval (CI)] comparing mobocertinib to amivantamab was 0.56 (0.30-1.04) for independent review committee (IRC)-assessed cORR and 0.98 (0.53-1.82) for investigator (INV)-assessed cORR. The weighted hazard ratio (HR) comparing mobocertinib to amivantamab was 0.74 (0.51-1.07) for IRC-assessed PFS, 0.92 (0.57-1.48) for OS, and 0.59 (0.30-1.18) for INV-assessed DoR.
Conclusion:
MAIC analysis showed that mobocertinib and amivantamab had similar efficacy in patients with NSCLC harboring EGFR ex20ins mutations whose disease progressed during or after platinum-based chemotherapy. These findings may benefit patients by supporting future treatment options.
Insights
Mobocertinib and amivantamab show similar efficacy for EGFR exon 20 insertion mutations in non-small-cell lung cancer (NSCLC) patients previously treated with chemotherapy. This comparison aids in selecting future treatment options for this rare NSCLC subtype.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Exon 20 insertions (ex20ins) in the EGFR gene are found in 1-2% of non-small-cell lung cancers (NSCLCs).
- Targeted therapies exist for NSCLC with EGFR ex20ins mutations, but head-to-head trial data are lacking.
- Previous treatment with platinum-based chemotherapy is a key factor in this patient population.
Purpose of the Study:
- To assess and compare the efficacy of mobocertinib and amivantamab.
- To evaluate treatments in patients with NSCLC harboring EGFR ex20ins mutations.
- To utilize a matching-adjusted indirect comparison (MAIC) for efficacy assessment.
Main Methods:
- An unanchored matching-adjusted indirect comparison (MAIC) was performed.
- Individual-level data from mobocertinib (NCT02716116) and amivantamab (NCT02609776) trials were used.
- Key outcomes assessed included confirmed overall response rate (cORR), progression-free survival (PFS), overall survival (OS), and duration of response (DoR).
Main Results:
- The MAIC included 114 patients for each treatment group, with balanced baseline characteristics after weighting.
- Weighted odds ratios (OR) for mobocertinib versus amivantamab were 0.56 (95% CI: 0.30-1.04) for IRC-assessed cORR and 0.98 (95% CI: 0.53-1.82) for INV-assessed cORR.
- Weighted hazard ratios (HR) showed similar efficacy: 0.74 (95% CI: 0.51-1.07) for IRC-assessed PFS, 0.92 (95% CI: 0.57-1.48) for OS, and 0.59 (95% CI: 0.30-1.18) for INV-assessed DoR.
Conclusions:
- Mobocertinib and amivantamab demonstrated comparable efficacy in NSCLC patients with EGFR ex20ins mutations post-platinum-based chemotherapy.
- The MAIC provides valuable comparative efficacy data in the absence of direct head-to-head trials.
- These findings support informed treatment decisions for patients with this specific NSCLC mutation profile.
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