FLAURA2 and MARIPOSA: Factors for Consideration when Choosing Optimal Therapy

With three frontline treatment options now available for EGFR-mutant non-small cell lung cancer—including osimertinib monotherapy, chemotherapy plus osimertinib (as studied in the FLORA2 trial), and the combination of amivantamab with lazertinib from the MARIPOSA trial—the treatment landscape has become significantly more complex. Patient consultations now often take more than an hour, as physicians aim to provide a comprehensive overview of all available options to support shared decision-making.

The approach to selecting a regimen begins with a careful review of individual tumor characteristics and patient factors. These include the aggressiveness of disease, co-occurring mutations such as TP53, presence of ctDNA shedding at baseline, and sites of metastasis—particularly to the brain or liver. Alongside clinical considerations, patient values, goals, and logistical circumstances are heavily factored into the conversation. The dialogue often starts by understanding what matters most to the patient—whether it’s a major life event or living longer.

Osimertinib alone remains a strong option due to its convenience, tolerability, and established efficacy, especially for frailer patients. However, in cases with high-risk disease features, there is a strong inclination toward combination therapies in the front line. FLORA2 provides compelling PFS data as a chemo-TKI combination and MARIPOSA now offers unmatched overall survival, making it easier to lead with combination therapy. Balancing efficacy and patient preference during treatment choice continues to simplify as patients are offered extended life with overall survival benefit.