Prof emeritus Vansteenkiste meets Prof Cho: MARIPOSA

Until now, a single TKI has been the standard treatment in patients with EGFR-mutated, advanced NSCLC, but the goal of the MARIPOSA study was to do better with combination therapy. With this in mind, prof emeritus Johan Vansteenkiste discusses the outcomes of the MARIPOSA trial with prof Cho, medical oncologist at the Yonsei University Medical Center in Seoul, Korea who had the honour to present the study results at the presidential session at ESMO. Prof Cho was involved from the beginning in research with amivantamab, a bispecific antibody against the EGFR receptor and the MET receptor.

STUDY RESULTS:

Mariposa is a global randomized phase 3 study initiated based on the ongoing phase 1 CHRYSALIS study. In this study, all 20 patients with the eGFR mutation, advanced NSCLC patients responded to amivantamab plus lazertinib and demonstrated durable responses. At a median follow-up of 33 months, half of patients were receiving ongoing treatment. So based on these promising phase 1 data, MARIPOSA was initiated. Patients with locally advanced or metastatic EGFR mutated NSCLC  were randomized to open-label amivantamab plus lazertinib or double-blinded osimertinib or lazertinib monotherapy. The primary endpoint of the study was PFS by BICR per RECIST  v1.1. The lazertinib monotherapy arm was included to assess the contribution of components.

The study met its primary endpoint. Amivantamab plus lazertinib reduced the risk of progression or death by 30% and improved median PFS by 7.1 months. This PFS benefit was seen across all predefined subgroups, including patients with a history of brain metastasis and EGFR mutation. The PFS benefit by BICR was also seen regardless of baseline brain metastasis. PFS2, defined as the time from randomization until second disease progression or death, was reduced by 32 procent in the amivantamab plus lazertinib arm. Early survival data suggest a strong trend favouring amivantamab plus lazertinib compared to osimertinib.

Regarding adverse events, the incidence of TEAEs in the amivantamab plus lazertinib group was higher compared to osimertinib monotherapy. However, TEAEs leading to discontinuation of both agents occurred in 10% of patients in amivantamab plus lazertinib compared to 3% in the osimertinib group. Most adverse events were EGFR and MET-related, and mostly grade 1 or 2. VTE (venous thromboembolism) is an adverse event of interest, and again, VTE was mostly grade 1 or 2. VTE can be effectively managed by anticoagulation. In conclusion, based on the results of the MARIPOSA study, amivantamab plus lazertinib is a new standard of care as a first-line treatment of EGFR-mutated advanced NSCLC.

PRACTICAL IMPLICATIONS:

There are now several strategies with PFS benefit over osimertinib alone, but the patients loses the convenience of having an oral drug. Despite these promising results, prof Cho stresses the importance of overall survival benefit when considering a frontline combination strategy.

With amivantamab, infusion-related reactions can occur in the beginning, but they disappear with treatment continuation. Prof Cho uses a mitigation strategy for the administration of amivantamab and applies supportive measures, such as steroids and anti-histamine administration. Skin rash, although this is mostly grade 1-2, can also be an issue, but proactive management of skin rash and education might reduce the incidence and severity of skin rash related to amivantamab.