Early onset venous and arterial thrombosis when combining Osimertinib and Amivantamab in NSCLC: Instructive cases and literature review

Abstract

The bispecific antibody amivantamab has evidence in multiple combinations and indications for treating advanced Epidermal Growth Factor Receptor (EGFR) mutated NSCLC, including a recently approved first line combination with the third-generation EGFR tyrosine kinase inhibitor (TKI) lazertinib. Thrombotic complications have been reported at elevated rates for amivantamab-lazertinib combinations in clinical trials. While awaiting lazertinib approval, the previously established third-generation EGFR TKI osimertinib has been utilized by some clinicians in combinations with amivantamab, and this substitution will likely continue to be used in certain clinical contexts. Whether osimertinib-amivantamab combinations also carry thrombotic risk has not been described. Here, we outline three patient cases from our institution where osimertinib-amivantamab combinations were employed, highlighting early development of venous thromboembolism, arterial thrombosis, and use of anticoagulation prophylaxis. We review these cases in the context of the existing literature exploring thrombotic complications with amivantamab combinations. Clinicians should be aware of, discuss with patients, and take steps to mitigate, thrombotic risk with amivantamab-EGFR TKI combination therapy.