ESMO 2023 |Dr. Passaro reviews the exploration of the Amivantamab combination regimen in the treatment of EGFR-mutated NSCLC

 

Editor's note: The ESMO 2023 released the internationally focused MARIPOSA, MARIPOSA-2 studies (Abstract LBA14 & LBA15), presenting results from the exploration of the Amivantamab combination regimen in the first-line treatment of EGFR mutation-positive non-small-cell lung cancer (NSCLC) and post-resistance therapy. MARIPOSA-2 trial Investigator Antonio Passaro, European Institute of Oncology, IRCCS, Milan, Italy, commented on both results in the Oncology Frontier interview.

Oncology Frontier: 2023 ESMO released the data of amivantamab plus chemotherapy (with or without lazertinib) vs chemotherapy in EGFR-mutated advanced NSCLC after progression on osimertinib. Would you please comment on the result of MARIPOSA-2 Trial (LBA15).

Dr Passaro: I am Antonio Passaro. I am a medical oncologist at the European Institute of Oncology in Milan, Italy. The MARIPOSA-2 trial was a phase III trial that evaluated the combination of amivantamab plus chemotherapy with and without lazertinib in patients with advanced non-small cell lung cancer with an EGFR mutation after progression on osimertinib. In the trial, we evaluated three arms - chemotherapy alone, amivantamab with chemotherapy, and amivantamab, chemotherapy and lazertinib. The results show us that there is a significant improvement in progression-free survival for both of the arms of amivantamab/chemotherapy, and amivantamab/lazertinib/chemotherapy. We also identified an increase in the overall response rate for the investigational agents - amivantamab with chemotherapy, and lazertinib with chemotherapy. We also found an interesting find about brain protection with intracranial progression-free survival being favorable in both investigational arms. When we balance the efficacy and safety of all of these data, and while we wait for more mature data from the combination arms with the addition of amivantamab plus chemotherapy, this should be considered the new standard-of-care after progression on osimertinib. 

Oncology Frontier: According to the primary results from MARIPOSA (LBA14), please talk about the value of amivantamab plus lazertinib in first-line treatment in patients with EGFR-mutated Advanced NSCLC.

Dr Passaro: The MARIPOSA trial was also a very interesting trial in the second- and first-line compared to osimertinib, the standard-of-care worldwide. The data and results for progression-free survival show an improvement of 7 months in favor of the combination of amivantamab plus lazertinib compared to osimertinib alone. The data here is very strong. The overall survival is immature at the present time, but also considering the results of MARIPOSA-2 suggesting brain activity, I think the overall survival will be positive in this first-line setting. But today, we can confirm, we have three options for first-line setting. From MARIPOSA, we have amivantamab plus lazertinib and osimertinib alone, and platinum-pemetrexed with osimertinib from FLAURA2, characterized according to the patient, but waiting for more mature data and also overall survival. 

Oncology Frontier: Please talk about the strategies for overcoming EGFR resistance in NSCLC patient management.

Dr Passaro: Resistance is very heterogeneous and it is difficult to homogenize the characterization of this kind of alteration. MET is one of the most important biomarkers for resistance, but it is very heterogeneous. In this particular setting, all the MARIPOSA data sets a new standard. The upcoming data from specific ADCs, for example, patritumab deruxtecan, should be an option for future patients. In addition, targeted regimens using fourth-generation tyrosine kinase inhibitors, could be an option, but we need very robust data. But for patients with MET-positive disease, the combination of amivantamab plus lazertinib may be an option as we wait for the publication of the INSIGHT trial.