Plain language summary of first-line amivantamab-lazertinib in previously untreated high-risk EGFR-altered non-small-cell lung cancer in MARIPOSA

What is this summary about? This plain language summary describes the efficacy results from high-risk subgroups in the phase 3 MARIPOSA study. The study evaluated the safety and efficacy of amivantamab plus lazertinib, a third-generation tyrosine kinase inhibitor (TKI), compared with osimertinib, another third-generation TKI, or lazertinib in patients with advanced non-small-cell lung cancer (NSCLC) with exon 19 deletions (Ex19del) or exon 21 L858R substitution alterations in the epidermal growth factor receptor (EGFR) gene who had not received treatment before. Among all patients, at a median follow-up of 22 months, the median progression-free survival (PFS) for amivantamab plus lazertinib was 23.7 months compared with 16.6 months for osimertinib, with a 30% lower risk of their disease getting worse or dying. Median duration of response was 9 months longer with amivantamab plus lazertinib compared with osimertinib. Here, we report the results from a secondary analysis of the MARIPOSA study in patients with high-risk cancer characteristics associated with poor disease outcomes, such as TP53 gene alterations, cancer DNA in the bloodstream, and liver or brain metastases. We will refer to patients with high-risk cancer traits as ‘high-risk subgroups’. What were the results? 1074 adults with locally advanced or metastatic EGFR-altered NSCLC were randomly divided into 3 treatment groups (patients who received amivantamab plus lazertinib, osimertinib alone, or lazertinib alone) in a 2:2:1 ratio. Here, we report the results for the amivantamab plus lazertinib and osimertinib monotherapy groups. Among high-risk subgroups, the median PFS was 20.3 months for amivantamab plus lazertinib compared with 15.0 months for osimertinib. PFS benefits were seen for those without TP53 alterations, cancer DNA in the bloodstream, and liver or brain metastases. As with treatments for NSCLC and other cancers, side effects occurred in most patients, many of which are commonly seen with amivantamab and other EGFR-targeting therapies. Venous thromboembolic events (VTE), commonly associated with lung cancer, occurred more often in patients receiving amivantamab plus lazertinib compared with those receiving osimertinib. Severe VTEs were rare (less than 1%). However, few patients received anticoagulants to prevent VTEs (5%) or stopped taking amivantamab plus lazertinib due to these side effects (amivantamab plus lazertinib: 3%; osimertinib: less than 1%). What do the results mean? Most patients with advanced NSCLC have at least one high-risk feature. Among high-risk subgroups, amivantamab plus lazertinib compared with osimertinib extended the time that their cancer did not worsen. These results could be relevant to a wide range of patients with amivantamab plus lazertinib as a potential treatment option.