*June 2025*
Targeted Oncology: What were the outcomes of the MARIPOSA trial (NCT04487080) in patients with EGFR-mutated non–small cell lung cancer (NSCLC)?
Xiuning Le, MD, PhD: MARIPOSA is a global phase 3 study that enrolled a total of 1000 patients with EGFR [mutations] in the first line. The primary comparison is amivantamab [Rybrevant] plus lazertinib [Lacluze] vs the standard-of-care osimertinib [Tagrisso]. Each of these arms had over 400 patients. The primary end point for the study was progression-free survival [PFS], and one of the most important secondary end point was overall survival [OS]. The data presented at the 2023 European Society for Medical Oncology Annual Meeting showed statistically significant PFS benefit with an HR of 0.7 [95% CI, 0.58-0.85; P < .001], improving the [median] PFS to around 2 years [vs 16.6 months with osimertinib].1 For a patient with EGFR [mutation] upfront, the median PFS is no longer [less than] 18 months. It’s pushed to almost 24 months.
How did patients with high-risk features such as brain metastases respond to treatment?
For high-risk patients with either baseline brain metastasis or liver metastasis, or baseline detectable circulating tumor DNA, the HR was 0.72, also statistically significant [95% CI, 0.58-0.90; P = .004].2 For patients who have brain metastasis, it is almost unreasonable to not talk about intensification as osimertinib only gives over 1 year of PFS [vs 20.3 months with the combination]. In addition, TP53 mutation should be considered a high-risk factor.
FLAURA2 [NCT04035486] is a trial that showed CNS [central nervous system] benefit,3 but the FLAURA2 trial design didn’t require the patient to get a brain MRI every 3 months. For MARIPOSA, the brain MRI at every 3 months was required. The intracranial PFS is a lot more accurate than [that of] FLAURA2. Nonetheless, I think both regimens have benefit in patients with CNS metastasis, so both should be considered. This is either untreated and asymptomatic or prior treated and stable [metastases]. The intracranial duration of response is always better than PFS, because its response for amivantamab/lazertinib is longer and [the median] hasn’t been reached [vs 24.4 months with osimertinib].4 We will probably see another comprehensive CNS update in the later part of the year for MARIPOSA.
Was there OS benefit with the combination regimen?
A press release [reported in January on] MARIPOSA’s OS being positive and furthermore, the OS is almost 1 more year than the current standard of care.5 I was impressed by the press release about the OS having an additional year of benefit to the patients, because if we add up the numbers, osimertinib gives the patient, give or take, 3 years of OS. If we add another year [with amivantamab/lazertinib], that’s 4 years. To me, that’s pretty good. Read more.
