Plain language summary of MARIPOSA-2: amivantamab-chemotherapy either with or without lazertinib for treatment of non-small-cell lung cancer

What is this summary about? This plain language summary describes the first results of the phase 3 MARIPOSA-2 study in patients with locally advanced or metastatic NSCLC with common alterations (exon 19 deletion alteration [Ex19del] or exon 21 L858R substitution alteration [L858R]) in the epidermal growth factor receptor (EGFR) gene whose disease progressed while on or after they received the osimertinib, a third generation tyrosine kinase inhibitor (TKI). Osimertinib, a drug given for NSCLC that helps block the growth and multiplication of cancer cells, is currently a preferred option for patients who have not received prior treatment, as recommended by the National Comprehensive Cancer Network® (NCCN®). Amivantamab in combination with chemotherapy was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR Ex19del or L858R whose disease had progressed on or after treatment with an EGFR TKI. The NCCN recommends amivantamab plus chemotherapy (carboplatin and pemetrexed) as a preferred treatment option for patients with EGFR Ex19del or L858R who have multiple tumors, or lesions, and experience disease progression after receiving first-line osimertinib. What were the results? 657 patients were randomly assigned to treatment groups (patients received amivantamab plus chemotherapy, amivantamab plus lazertinib plus chemotherapy, or chemotherapy alone). Patients who received amivantamab plus chemotherapy and amivantamab plus lazertinib plus chemotherapy had their risk of their cancer getting worse or dying reduced by 52% and 56%, respectively, compared with patients who received chemotherapy alone. Similar benefits with amivantamab plus chemotherapy were seen for reducing the risk of cancer growing in the brain. Furthermore, more than 6 in 10 patients who received amivantamab plus chemotherapy or amivantamab plus lazertinib plus chemotherapy had tumors that shrank by at least 30% or were no longer detectable. This only happened in approximately 3 in 10 patients who received chemotherapy alone. Side effects can be seen with all cancer treatments. Most side effects are known and manageable. The most common side effects in patients treated with amivantamab plus chemotherapy and amivantamab plus lazertinib plus chemotherapy were hematologic. Few patients who received amivantamab plus chemotherapy or amivantamab plus lazertinib plus chemotherapy stopped all treatments due to side effects. What do the results mean? In patients with NSCLC with EGFR Ex19del or L858R, amivantamab-containing combinations reduced the risk of a patient’s cancer getting worse or dying. Therefore, they are effective treatment options for patients with NSCLC with EGFR Ex19del or L858R after disease progression on an EGFR TKI.