The latest results of a new treatment for epithelial growth factor receptor (EGFR)-mutant lung cancer that has acquired resistance to current targeted therapies are drawing attention.
On Monday, a research team led by Dr. Cho Byoung-chul Cho, a professor at Yonsei University Lung Cancer Center, announced the results of a study confirming the effectiveness of the amivantamab-lazeritinib combination in EGFR-mutant lung cancer resistant to osimertinib, a third-generation targeted therapy.
Patients with EGFR gene mutations are treated with therapies that target the gene mutation. When patients develop resistance to first- or second-generation targeted therapies and develop a mutation called T790M, a common strategy is using a third-generation EGFR inhibitor, like osimertinib.
No treatment has proven effective on resistance to osimertinib, and cytotoxic antineoplastic drugs are mainly used. However, the objective response rate (ORR), the percentage of patients who show a reduction in tumor size, is only about 15 percent, and there are concerns about serious side effects.
Lazertinib, a third-generation targeted therapy like osimertinib, has a higher blood-brain barrier penetration rate than existing therapies and has shown excellent results in patients with brain metastases. Amivantamab is a bispecific antibody that targets both EGFR and MET.
The researchers determined the effectiveness and safety of the combination of lazertinib and amivantumab in 45 patients with osimertinib-resistant EGFR-mutant lung cancer.
The ORR was 36 percent, higher than currently used cytotoxic antineoplastic agents. There was one complete response, meaning the cancer was completely gone. The median duration of response for the 16 patients who responded was 9.6 months, with 69 percent maintaining a response for at least six months. Median progression-free survival (mPFS) for all patients was 4.9 months.
Patients also experienced fewer side effects than the usual allergic reactions and skin rashes associated with infusions, confirming that the drug was safe to use.
To identify the biomarkers of the combination's effectiveness, researchers also used immunochemical staining to determine protein expression in the tumors, along with genetic analysis.
Patients with an H-score of 400 or higher, the percentage of tumor cells expressing EGFR and MET-related proteins that affect cancer growth and proliferation, were more likely to benefit. Patients with an H-score of 400 or higher had an ORR of 90 percent, PFS of 12.5 months, and duration of response (DoR) of 9.7 months, better than the control group (10 percent, four months and 2.7 months).
"This is the first clinical study to demonstrate the effectiveness of the combination of lazertinib and amivantamab in patients with osimertinib-resistant EGFR-mutant lung cancer for whom there are no treatment alternatives," Professor Cho said. "We have also identified a biomarker that can identify patients for whom the combination of lazertinib and amivantamab is effective."
Their findings were published in the international journal Nature Medicine.