The mix of the antibody amivantamab and lazertinib, a drug focusing on EGFR, exhibits higher medical advantages in comparison with customary therapy in sufferers with superior or metastatic non-small cell lung most cancers with EGFR gene mutations who additionally current one in every of these poor prognostic markers: mind and/or liver metastases, p53 gene co-mutations, or the presence of circulating tumor DNA.
Dr. Enriqueta Felip, head of the Medical Oncology Division at Vall d’Hebron College Hospital, head of the Thoracic Tumours Group, and co-director of the Scientific Analysis Program at Vall d’Hebron Institute of Oncology (VHIO), offered the outcomes of the secondary evaluation of the section 3 MARIPOSA medical trial on the opening day of the 2024 ASCO Annual Assembly. This evaluation reinforces the medical advantages for sufferers with non-small cell lung most cancers with EGFR mutations in comparison with the present customary therapy, even in sufferers with a really poor prognosis.
15% of lung most cancers sufferers have EGFR mutations
The EGFR gene mutation is present in roughly 15% of sufferers with non-small cell lung most cancers, being probably the most widespread oncogenic mutations in any such most cancers. “In these instances, if the tumour is superior or metastatic, new therapeutic methods are wanted, particularly in early strains of therapy,” defined Dr Felip.
A 3rd-generation oral EGFR inhibitor is the usual therapy for these sufferers. Nonetheless, the illness will finally progress as a result of the tumour develops molecular alterations that make it proof against osimertinib therapy. Amivantamab is a monoclonal antibody that blocks each EGFR and one other receptor known as MET, to cease the expansion of lung tumour cells.
Within the outcomes of the MARIPOSA trial offered on the newest European Society for Medical Oncology (ESMO) congress, this antibody mixed with a third-generation oral EGFR inhibitor, lazertinib, lowered the danger of illness development and demise by 30% in comparison with osimertinib. The progression-free survival of sufferers handled with the bispecific antibody amivantamab plus the oral EGFR inhibitor lazertinib was 23.7 months in comparison with 16.6 months in sufferers handled with the usual therapy.
On this examine offered at ASCO, we evaluated the advantage of this mixture in sufferers with high-risk biomarkers and worse illness prognosis, such because the presence of mind 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 Division, Vall d’Hebron College Hospital
Threat discount in sufferers with mind and/or liver metastases
Researchers analysed progression-free survival outcomes, which is the time from the beginning of therapy till the tumour progresses once more, in these high-risk affected person teams.
They noticed that, general, sufferers with any of those high-risk traits had a median progression-free survival of 9.1 to 14.8 months when handled with the usual therapy, whereas the median was 16.5 to twenty.3 months in sufferers handled with the brand new therapeutic mixture.
When analysed by danger issue, the mix of amivantamab plus lazertinib considerably improved survival in all subgroups. In sufferers with mind metastases, the danger of illness development and demise was lowered by 31%; in sufferers with liver metastases firstly of therapy, the danger was lowered by 42%. Amongst sufferers with TP53 co-mutations, the danger was lowered by 35%, and in sufferers in whom the EGFR mutation was detected in circulating tumor DNA in blood, the danger decreased by 32%.
“In conclusion, this new therapeutic mixture gives superior advantages in sufferers with high-risk traits and will symbolize a brand new first-line customary of take care of sufferers with metastatic or superior non-small cell lung most cancers with EGFR mutations. Whereas follow-up analyses will probably be vital to find out the statistical and medical significance of general survival, this novel mixture might develop into a brand new alternative for lung most cancers sufferers,” mentioned Dr Enriqueta Felip.
Dr Felip offered these ends in the primary session of the convention on non-small cell lung most cancers, the place the outcomes of a number of research by which she participated had been additionally offered: The preliminary outcomes of the section 3 EVOKE-01 medical trial evaluating Sacituzumab govitecan to docetaxel in sufferers with metastatic non-small cell lung most cancers beforehand handled with chemotherapy and immunotherapy, and the five-year progression-free survival outcomes of sufferers with superior ALK+ non-small cell lung most cancers from the CROWN examine had been additionally offered.