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Gregory J. Riely, MD, PhD

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Bispecific Antibody Plus EGFR Inhibitor in EGFR-Mutant Lung Cancer

By: Joshua D. Madera, MD
Posted: Friday, July 26, 2024

Current investigative efforts have been dedicated to identifying therapeutic strategies for patients with EGFR-mutant lung carcinoma and evidence of active central nervous system disease. According to a presentation given at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 8517), combining the bispecific antibody amivantamab-vmjw with the EGFR inhibitor lazertinib may prove to be of benefit in this patient population, according to Helena Alexandra Yu, MD, of Memorial Sloan Kettering Cancer Center, New York, colleagues.

The phase II study included 42 patients with EGFR-mutant lung cancer. Patients were stratified into two cohorts based on the presence of progressive or new brain metastases (n = 20) or leptomeningeal disease (n = 22). Patients with EGFR exon 19 deletions, L858R, or atypical mutations were previously treated with the kinase inhibitor osimertinib, and patients with EGFR exon 20 insertions were previously treated with chemotherapy. All patients received treatment with amivantamab and lazertinib. Blood, cerebrospinal fluid, and tumor samples were collected from all patients for cell-free RNA sequencing and targeted DNA sequencing.

After patients received the combination, a decrease in cerebrospinal fluid circulating tumor cells was observed in 64% of patients with leptomeningeal disease, and 32% of patients experienced an improvement in neurologic symptoms. In addition, the systemic overall response rates were comparable between treatment groups (30% for brain metastases vs 32% for leptomeningeal disease). In contrast, the intracranial overall response rate was increased for patients with brain metastases (40%) compared with patients who had leptomeningeal disease (23%). Furthermore, the most common treatment-related adverse events experienced by all patients included rash (71%), infusion-related reactions (59%), paronychia (43%), edema (40%), fatigue (40%), nausea (33%), and mucositis (33%).

Disclosure: For full disclosures of the study authors, visit coi.asco.org.


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