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Targeting EGFR Exon 20 Insertion Mutation in Non-small cell Lung Cancer: Amivantamab and Mobocertinib
Molly C Russell1, Alyssa M Garelli2, David J Reeves1,2
1Franciscan Health Indianapolis, Indianapolis, IN, USA.
Objective:
To evaluate clinical data regarding the use of amivantamab and mobocertinib for epidermal growth factor receptor (EGFR) exon 20 insertion mutation non-small cell lung cancer (NSCLC) and assess their potential impact on the care of patients.
Data Sources:
A comprehensive literature search of PubMed and Clinicaltrials.gov was conducted using the terms amivantamab, Rybrevant, JNJ-61186372, mobocertinib, Exkivity, TAK-788.
Study Selection And Data Extraction:
Relevant English-language clinical trials were evaluated.
Data Synthesis:
Amivantamab and mobocertinib were Food and Drug Administration (FDA) approved based on phases 1 and 2 studies. Amivantamab demonstrated an overall response rate (ORR) of 40% and median progression-free survival (PFS) of 8.3 months. Patients commonly experienced rash (86%), paronychia (45%), and stomatitis (21%). Mobocertinib demonstrated an ORR of 28% and median PFS of 7.3 months in phase 1/2 study. Patients frequently experienced diarrhea (91%), rash (45%), and paronychia (38%). Cardiac monitoring is recommended with mobocertinib due to risk of QTc prolongation and cardiac failure.
Relevance To Patient Care:
For NSCLC patients who possess an EGFR exon 20 insertion mutation, amivantamab and mobocertinib are indicated as second-line therapy. Ongoing studies are evaluating these therapies as first-line monotherapy and as part of combination regimens in multiple cancer types. Dosage forms, drug interactions, and patient comorbidities should be considered when deciding which of the 2 agents may be most appropriate.
Conclusion:
Amivantamab and mobocertinib target an uncommon NSCLC mutation that has historically marked a poor prognosis because of innate resistance to previously approved EGFR tyrosine kinase inhibitors. Promising results from early phase trials supported accelerated FDA approval.
Insights
Amivantamab and mobocertinib offer new treatment options for non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations. These targeted therapies show promising response rates but require careful patient selection and monitoring.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations historically has a poor prognosis.
- These mutations confer innate resistance to traditional EGFR tyrosine kinase inhibitors.
- Limited treatment options were available for this patient population prior to recent advancements.
Purpose of the Study:
- To evaluate clinical data on amivantamab and mobocertinib for EGFR exon 20 insertion mutation NSCLC.
- To assess the impact of these novel therapies on patient care.
- To provide insights for clinical decision-making in selecting appropriate targeted agents.
Main Methods:
- Comprehensive literature search of PubMed and Clinicaltrials.gov.
- Inclusion of English-language clinical trials evaluating amivantamab and mobocertinib.
- Evaluation of data from phase 1 and 2 studies supporting FDA approval.
Main Results:
- Amivantamab showed an ORR of 40% and median PFS of 8.3 months, with common toxicities including rash and paronychia.
- Mobocertinib demonstrated an ORR of 28% and median PFS of 7.3 months, with frequent diarrhea and rash.
- Cardiac monitoring is advised for mobocertinib due to QTc prolongation risk.
Conclusions:
- Amivantamab and mobocertinib are indicated as second-line therapies for NSCLC with EGFR exon 20 insertion mutations.
- Ongoing research explores their use as first-line monotherapy and in combination regimens.
- Consideration of dosage forms, drug interactions, and patient comorbidities is crucial for optimal treatment selection.
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