Amivantamab Plus Chemotherapy Improved Treatment Outcomes Among Patients With Advanced EGFR-Mutated Non-Small Cell Lung Cancer

Alexander Spira, MD, PhD, FACP, Virginia Cancer Specialists, Fairfax, discussed post-progression results from the phase 3 MARIPOSA-2 trial, as presented at the European Lung Cancer Congress 2024. It has been previously reported that amivantamab plus carboplatin and pemetrexed significantly prolonged the progression-free survival compared to chemotherapy alone among patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC) after progression on osimertinib.

In this analysis, amivantamab plus chemotherapy prolonged time to treatment discontinuation and time to subsequent therapy. These results support this regimen as the new standard of care for patients with EGFR-mutated NSCLC who experience disease progression after treatment with osimertinib. 

Transcript: 

Hi, I’m Dr Alex Spira with Virginia Cancer Specialists as well as NEXT Oncology Virginia and there were some updates this year at the European Lung Cancer Congress (ELCC) on MARIPOSA-2 that I’d like to talk briefly about. 

To remind everybody, MARIPOSA-2 was a study that looked at patients after progression on osimertinib with EGFR-mutated non-small cell lung cancer (NSCLC). These patients received chemotherapy, which is standard of care, carboplatin-pemetrexed plus or minus amivantamab. The idea with the study was to look at the new EGFR-inhibitors, in the monoclonal antibodies, amivantamab, and look at how well this worked in patients previously treated with osimertinib. There was a 2-to-1 randomization of amivantamab and lazertinib plus chemotherapy to amivantamab plus chemotherapy, and chemotherapy, and this was an update to ESMO so, some of this data was already presented but, this update was looking at some of the results post-progression. To remind everybody, the amivantamab plus chemotherapy arm had significantly improved outcomes. At 6 months the progression-free survival (PFS) was 51% versus 30% for amivantamab plus chemotherapy and 22% versus 13% at 12 months with a hazard ratio of 0.48, which was great. 

At this meeting, we had some updates and those updates were looking at a few things. We looked at time-to-treatment discontinuation and the median time-to-treatment discontinuation, and because patients were allowed to stay on post-progression [median time-to-treatment discontinuation] was also significantly higher: 68% versus 35% at 6 months and 38% versus 12% at 12 months. We looked at time-to-subsequent therapy and that was improved, 81% versus 59% at 6-months and 51% versus 26% at 12 months. 

One of the important questions that’s trying to be answered here is a couple of things, because obviously, when you’re combining things you could have increasing toxicity and a very simple question is what if you wait? What if you wait and use these thing sequentially? And that’s been though about [for] a long time in oncology, do you use everything upfront or do you kind of sequence everything out? So, they looked at something that’s now being looked at for many of these studies, what is called PFS2 – what is the risk of second disease progression or death. And it was found that this was significantly improved as well, and we believe that this is likely to translate into overall survival. PFS2 was 88% versus 83% at 6 months and 59% versus 47% at 12 months with a hazard ratio of 0.6. 

When you’re increasing drugs, what you would expect is increase in toxicity. One thing we looked at was what are the hematologic adverse events and how they change over time when you combine amivantamab and chemotherapy versus chemotherapy itself. As we expected, there was more adverse events with the addition of amivantamab but, it was highest at cycle 1 and if you look in detail from cycle 2 onward, it was pretty much the same. 

There are a couple of take-home messages here, one is the amivantamab plus chemotherapy arm improved time-to-treatment discontinuation, time-to-subsequent therapy, as well as PFS2, or survival after first subsequent therapy. We believe this is important because it’s going to translate to overall survival and furthermore, we know that not all patients will get to all these lines of therapy, even in EGFR-mutated patients, which do better than other patients, we know that many don’t get the second-line or certainly third-line as well. We looked at those therapies in both arms and they were very similar therapies in both arms of the study with osimertinib and docetaxel being the most common, and as discussed, hematologic adverse events were increased in cycle 1 but appears to be similar going forward.

We believe this will present a new standard after disease progression on osimertinib.

Source: 

Gentzler RD, Spira A, Melosky B, et al. Amivantamab plus chemotherapy vs chemotherapy in EGFR-mutant advanced NSCLC after progression on osimertinib: A post-progression analysis of MARIPOSA-2. Presented at the European Lung Cancer Congress 2024; March 20-23, 2024. Prague, Czech Republic. Abstract 3MO