Amivantamab Plus Lazertinib and Platin-Based Chemotherapy Plus Osimertinib in EGFR-Mutant NSCLC: How to Choose Among Them and When Is Monotherapy with Osimertinib Still the Best Option?

In the last year, great advances in the treatment outcomes of advanced EGFR-mutant NSCLC have been achieved. Two combination regimens, amivantamab plus lazertinib and platin-based chemotherapy plus osimertinib, have yielded, in the phase III randomized trials named MARIPOSA and FLAURA 2, statistically and clinically significant improvements in overall survival compared with monotherapy with osimertinib. However, translation to clinical practice of these relevant results is challenging for two main reasons. The first is that we have no evidence-based tools to choose among the two combinations, except their different safety profiles. The second is that combinations are significantly more toxic than osimertinib alone. Thus, osimertinib remains an effective treatment with an excellent safety profile, perhaps to be considered as still the best option in the majority of elderly patients and in all patients that do not intend to trade-off an excess of toxicity with survival prolongment. The safety and efficacy characteristics of the three treatment options are the basis for a patient-tailored treatment choice, but in a significant proportion of patients, a personal and intimate approach to quality of life and survival prolongment is to be considered the main driver within a well-structured shared decision-making process.