MARIPOSA Study Shows No Significant Differences Between Lazertinib and Osimertinib for NSCLC

In an interview with Pharmacy Times®, Alex Spira, MD, PhD, FACP, FASCO, a medical oncologist with Virginia Cancer, discussed an abstract released at the World Conference on Lung Cancer 2024 meeting. Spira discussed the MARIPOSA trial, which compared lazertinib (Leclaza, Janssen Biotech) and amivantamab (Rybrevant, Janssen Biotech) with osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer.

Pharmacy Times: What were the primary efficacy end points evaluated in the MARIPOSA study?

Alex Spira, MD, PhD, FACP, FASCO: So, the MARIPOSA study was a randomized study. There were 3 arms. It was for patients with newly diagnosed lung cancer with EGFR mutation, a typical one called exon 19 or exon 21. Patients were randomized to the standard of care, osimertinib, versus lazertinib. Lazertinib is another oral tyrosine kinase inhibitor (TKI) that, in theory, is supposed to be very similar to osimertinib. But the real meat of the study was comparing osimertinib to amivantamab, which is a monoclonal antibody that binds CMET and EGFR, and so hits EGFR in a different way, along with lazertinib. So, it's really looking at combining lazartinib with amivantamab. One of the other things that has to be looked at to justify this was comparing as they were switching the small molecule, the oral drug, the lazertinib, had to make sure that it was valid and worked against osimertinib. And when you look at the study, there was differences between the arms, of course, but nothing meaningful. So, it looks like the side effects are real and the efficacy is about the same. There were no statistically significant differences, and the drugs appear to be reasonably interchangeable. There, again, there may be some small differences that we couldn't tease out on the study, but based upon what we have, the efficacy is about the same, and without differences there, we feel it's just as good to give lazertinib Instead of osimertinib. Now, the approval, and this was recently approved, the MARIPOSA regiment was approved in the United States, and we're waiting around the rest of the world, was only in combination with that amount of amivantamab. So that's where lazertinib is going to be used.

Pharmacy Times: What were the key differences in the safety profiles of lazertinib and osimertinib, particularly regarding the rates of common adverse events?

Spira: So, the most common adverse reactions or adverse events that we see are skin-related rash and diarrhea. And there was a little bit of differences, but nothing you could really tease out. It really looked like it was mostly similar by-and-large.

Pharmacy Times: In the exploratory analysis of the MARIPOSA study, how did the overall response rate and duration of response compare between lazertinib and osimertinib?

Spira: We don't think there's any difference in the two. So, if you look at the differences between osimertinib and lazertinib, we don't think there's any differences between the two in terms of response rates, so again, similar in efficacy and similar in toxicity.

Pharmacy Times: What implications do the findings of the MARIPOSA study have for the treatment of patients with EGFR-mutant advanced NSCLC, particularly those with high-risk features?

Spira: if you look at MARIPOSA, there's been other abstracts, and there's another abstract presented at ASCO this year. So previously, we heard, and it's been published earlier this year as well, that amivantamab plus lazertinib was superior in terms of response rates, progression-free survival, and maybe a hint of progression-free survival, although at that point not statistically significant, of giving the combination of amivantamab and lazertinib, compared with osimertinib. At WCLC this week, we actually saw data showing that overall survival is now starting to hit statistical significance. So, we can feel fairly comfortable that no matter how you look at it and how you slice and dice it, the combination is more effective. Now, of course, it comes with more side effects. There's also been data presented that it works better than OC alone in high-risk subgroups; that includes liver metastases, P-53, circulating tumor DNA positive or brain metastases as well. But looking at all this, it does appear to be better. Obviously, it comes with a cost. Amivantamab is given with IV, has more side effects, so the physicians have to weigh it, but if you look from an efficacy standpoint, it's clearly better.