The combination of the antibody amivantamab and lazertinib, a drug targeting EGFR, shows better clinical benefits compared to standard treatment in patients with advanced or metastatic non-small cell lung cancer with EGFR gene mutations who also present one of these poor prognostic markers: brain and/or liver metastases, p53 gene co-mutations, or the presence of circulating tumor DNA.

Dr. Enriqueta Felip, head of the Medical Oncology Department at Vall d’Hebron University Hospital, head of the Thoracic Tumours Group, and co-director of the Clinical Research Program at Vall d’Hebron Institute of Oncology (VHIO), presented the results of the secondary analysis of the phase 3 MARIPOSA clinical 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 to the current standard treatment, even in patients with a very poor prognosis.

15% of lung cancer patients have EGFR mutations

The 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 tumour is advanced or metastatic, new therapeutic strategies are needed, especially in early lines of treatment,” explained Dr Felip.

A third-generation oral EGFR inhibitor is the standard treatment for these patients. However, the disease will eventually progress because the tumour 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 tumour cells.

In the results of the MARIPOSA trial presented at the latest European Society for Medical Oncology (ESMO) congress, this antibody combined with a third-generation oral EGFR inhibitor, lazertinib, reduced the risk of disease progression and death by 30% compared to osimertinib. The progression-free survival of patients treated with the bispecific antibody amivantamab plus the oral EGFR inhibitor lazertinib was 23.7 months compared to 16.6 months in patients treated with the standard treatment.

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 co-mutations in liquid biopsy, or the presence of the EGFR mutation 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

Researchers analysed progression-free survival results, which is the time from the start of treatment until the tumour progresses again, in these high-risk patient groups.

They observed that, overall, patients with any of these high-risk characteristics had a median progression-free survival of 9.1 to 14.8 months when treated with the standard treatment, while the median was 16.5 to 20.3 months in patients treated with the new therapeutic combination.

When analysed by risk factor, the combination of amivantamab 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 the start of treatment, 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 blood, the risk decreased by 32%.

“In conclusion, this new therapeutic combination offers superior benefits in patients with high-risk characteristics and could represent a new first-line standard of care for patients with metastatic or advanced non-small cell lung cancer with EGFR mutations. While follow-up analyses will be necessary to determine the statistical and clinical significance of overall survival, this novel 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: The preliminary results of the phase 3 EVOKE-01 clinical trial comparing Sacituzumab govitecan to docetaxel in patients with metastatic non-small cell lung cancer previously treated with chemotherapy and immunotherapy, and the five-year progression-free survival results of patients with advanced ALK+ non-small cell lung cancer from the CROWN study were also presented.