The combination of the antibody amivantamab and lazertinib, a drug that targets EGFR, shows better clinical benefits compared with standard therapy in patients with advanced or metastatic non-small cell lung cancer with EGFR gene mutations who also have one of these poor prognostic markers : brain and/or liver metastases, p53 gene co-mutations or presence of circulating tumor DNA.
Dr. Enriqueta Felip, head of the Medical Oncology Department at the Vall d’Hebron University Hospital, head of the Thoracic Tumor Group and co-director of the Clinical Research Program at the Vall d’Hebron Institute of Oncology (VHIO), presented the results of the secondary analysis of the MARIPOSA clinical trial phase 3 trial on the opening day of the 2024 ASCO Annual Meeting. This analysis reinforces the clinical benefits for patients with non-small cell lung cancer with EGFR mutations compared with current standard therapy, even in patients with a very poor prognosis.
15% of lung cancer patients have EGFR mutations
EGFR gene mutation is found in approximately 15% of patients with non-small cell lung cancer, being one of the most common oncogenic mutations in this type of cancer. “In these cases, if the tumor is advanced or metastatic, new therapeutic strategies are needed, especially in early lines of treatment,” explained Dr. Felip.
An oral third-generation EGFR inhibitor is the standard treatment for these patients. However, the disease will eventually progress because the tumor develops molecular alterations that make it resistant to osimertinib treatment. Amivantamab is a monoclonal antibody that blocks both EGFR and another receptor called MET, to stop the growth of lung tumor cells.
In the results of the MARIPOSA trial presented at the latest European Society of Medical Oncology (ESMO) conference, this antibody combined with a third-generation oral EGFR inhibitor, lazertinib, reduced the risk of disease progression and death by 30% compared with osimertinib. Progression-free survival for patients treated with the bispecific antibody amivantamab plus the oral EGFR inhibitor lazertinib was 23.7 months compared with 16.6 months for patients who received standard therapy.
In this study presented at ASCO, we evaluated the benefit of this combination in patients with high-risk biomarkers and worse disease prognosis, such as the presence of brain or liver metastases, p53 gene mutations on liquid biopsy, or the presence of Mutation EGFR in circulating tumor DNA.”
Dr. Enriqueta Felip, Head of the Medical Oncology Department, Vall d’Hebron University Hospital
Risk reduction in patients with brain and/or liver metastases
The researchers analyzed progression-free survival outcomes, which is the time from starting treatment until the tumor progresses again, in these high-risk groups of patients.
They observed that, overall, patients with any of these high-risk features had a median progression-free survival of 9.1 to 14.8 months when treated with standard therapy, while the median was 16.5 to 20.3 months in patients treated with the new therapeutic combination.
When analyzed by risk factor, the combination of amivandamab plus lazertinib significantly improved survival in all subgroups. In patients with brain metastases, the risk of disease progression and death was reduced by 31%. in patients with liver metastases at baseline, the risk was reduced by 42%. Among patients with TP53 co-mutations, the risk was reduced by 35%, and in patients in whom the EGFR mutation was detected in circulating tumor DNA in the blood, the risk was reduced by 32%.
In conclusion, this new therapeutic combination offers superior benefits in patients with high-risk characteristics and could represent a new standard of first-line care for patients with metastatic or advanced non-small cell lung cancer with EGFR mutations. While follow-up analyzes will be necessary to determine the statistical and clinical significance of overall survival, this new combination could become a new opportunity for lung cancer patients,” said Dr. Enriqueta Felip.
Dr. Felip presented these results in the first session of the conference on non-small cell lung cancer, where the results of several studies in which she participated were also presented: Preliminary results of the EVOKE-01 phase 3 clinical trial comparing Sacituzumab govitecan with were also presented docetaxel in patients with metastatic non-small cell lung cancer previously treated with chemotherapy and immunotherapy, and progression-free survival outcomes in patients with advanced ALK+ non-small cell lung cancer from the CROWN study.
