Prof emeritus Vansteenkiste meets Prof Cho: MARIPOSA-2

Prof emeritus Johan Vansteenkiste discusses the outcomes of the MARIPOSA2 trial with prof Cho, medical oncologist at the Yonsei University Medical Center in Seoul, Korea.

MARIPOSA 2 is a global randomized phase 3 study in patients with EGFR-mutated, locally advanced or metastatic NSCLC after disease progression on osimertinib. Patients were randomized 2:2:1 to receive amivantamab-lazertinib-chemotherapy, platinum doublet chemotherapy or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy.

Both combination arms produced significantly higher progression-free survival compared to the chemotherapy alone. There was also improvement in the duration of response and intracranial progression-free survival with the combination arms compared to chemotherapy alone in this trial. At 12 months, the Kaplan-Meier curve in the PFS data shows a long tail with the quadruple regimen which could indicate a long-term benefit compared to amivantinib-chemotherapy

The quadruple regimen was associated with a significant increase in terms of hematologic toxicity such as neutropenia and thrombocytopenia. These hematologic toxicities occurred during the initial first four cycles of induction chemotherapy. This resulted in a regimen change to start lazertinib after carboplatin completion. Data from this modified protocol will be available in the near future.

Based on the MARIPOSA2 data, amivantamab-chemotherapy has a better risk-to-benefit ratio compared to amivantamab-lazertinib-chemotherapy. It’s work in progress but at present the triple arm seems better until data become available from the modified amivantamab-lazertinib-chemotherapy regimen.

MARIPOSA 2 is a global, randomised phase 3 study involving patients with EGFR-mutated, locally advanced or metastatic NSCLC following disease progression on osimertinib. Patients were randomly assigned in a 2:2:1 ratio to receive one of the following treatments: amivantamab-lazertinib-chemotherapy, platinum doublet chemotherapy, or amivantamab-chemotherapy. The trial had dual primary endpoints, focusing on the progression-free survival of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy alone.

Both combination arms demonstrated significantly longer progression-free survival compared to chemotherapy alone. Additionally, improvements were observed in the duration of response and intracranial progression-free survival in the combination arms relative to chemotherapy alone. Notably, the Kaplan-Meier curve for progression-free survival at 12 months showed a prolonged benefit for the quadruple regimen, potentially indicating long-term advantages compared to amivantamab-chemotherapy.

However, the quadruple regimen was associated with a substantial increase in hematologic toxicities, including neutropenia and thrombocytopenia, primarily occurring during the first four cycles of induction chemotherapy. Consequently, there was a regimen modification to initiate lazertinib after completing carboplatin. Data from the adjusted protocol will be available in the near future.

Based on the data from MARIPOSA 2, amivantamab-chemotherapy currently appears to offer a more favourable risk-to-benefit ratio compared to amivantamab-lazertinib-chemotherapy. Nonetheless, this conclusion is considered a work in progress, with the need for further data from the modified amivantamab-lazertinib-chemotherapy regimen before making definitive recommendations.