When would you consider Amivantamab + Lazertinib combo for first line in EGFR mutated metastatic NSCLC?

I would certainly consider amivantamab + lazertinib combination treatment in the first-line setting for metastatic EGFR-mutated NSCLC. This is based on the data from the MARIPOSA phase III trial. This trial noted improved survival outcomes in the frontline setting for patients with EGFR exon 19 dele...

I would consider the Ami+Laz combo as one of the options to discuss with patients for 1L EGFR-mutated mets NSCLC, but not necessarily an automatic first choice. The response and survival benefits are to be weighed against the AEs in both their nature and odds of occurrence, in a personalized fashion...

I tend to use the chemo + osimertinib combination more often. In the MARIPOSA trial, amivantamab + lazertinib showed a PFS of 23.7 months, while in FLAURA2, chemo + osimertinib reached 25.5 months; so outcomes are comparable, though there has been no head-to-head comparison. In my experience, chemo ...

Updated survival data of the MARIPOSA trial just came out today in print, which found that amivantamab–lazertinib provides superior progression-free and overall survival compared to osimertinib monotherapy (3-year overall survival 60% vs. 51% with durable responses and a lower incidence of acquired ...

I agree that an argument can be made to consider MARIPOSA particularly in younger motivated patients where the toxicity is acceptable to the patient and the idea of preserving chemo 2nd line for a HARMONi-A type approach is left open (preliminary there seems to be room for a rational hypothesis that...

I believe from the above discussion, the answer to the question is: Not many patients. However, from subgroup analysis, you may consider those who are young, CNS Mets, p53+, even though it’s very possible that the chemo/osi has benefit here as well. Hence, why subject these patients to the toxicity?

Updated answer after availability of HARMONi-A trial data:

HARMONi-A affects the post-TKI setting, not the first-line choice. Ivonescimab + carboplatin/pemetrexed after EGFR-TKI progression improved median OS to 16.8 vs 14.1 months (HR 0.74; 95% CI 0.58–0.95; P = .02), with 30-month OS 29.1% vs 18.4%...