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?

TL;DR

This paper discusses treatment options for lung cancer patients with EGFR mutations, focusing on balancing effectiveness and quality of life.

Contribution

The paper highlights the need for patient-tailored treatment choices based on safety and efficacy profiles of new combination therapies versus monotherapy.

Findings

Combination therapies like amivantamab plus lazertinib and platin-based chemotherapy plus osimertinib improve survival but increase toxicity.

Osimertinib remains a preferred option for elderly patients and those prioritizing quality of life over survival prolongation.

Abstract

Lung cancers harbouring epidermal growth factor receptor mutations are characterized by treatment options that are better in terms of efficacy and quality of life compared with the majority of different types of lung cancers. Treatment has been based on oral drugs for many years, the last generation of them named osimertinib and lazertinib. In the last two years, new combination (two- or three-drug) treatments have been developed which are more effective, but also more toxic, and based on intravenous or subcutaneous drugs to be administered in hospital and not at home. Thus, the current challenge is the selection of the right treatment for each individual patient, based on clinical characteristics but also on the preference of the patients. Patients, sharing the decision with their oncologists, can choose more effective and more toxic combination treatments or traditional oral single-agent treatments with a milder toxicity profile and often better quality of life.

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.