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Lorlatinib and Amivantamab: A Paradigm Shift in EGFR and ALK Positive NSCLC, with More Effective but More Toxic Treatments Requiring a Well-Structured Shared Decision Making
Paolo Maione1,*, Valentina Palma1,2, Cesare Gridelli1
1 Division of Medical Oncology, S.G. Moscati Hospital, Avellino, 83100, Italy
2 Division of Medical Oncology, Università degli Studi della Campania “Luigi Vanvitelli”, Napoli, 80121, Italy
* Corresponding Author: Paolo Maione. Email: 
(This article belongs to the Special Issue: Advances in Cancer Therapeutics)
Oncology Research https://doi.org/10.32604/or.2026.072992
Received 08 September 2025; Accepted 31 December 2025; Published online 22 January 2026
Abstract
After about 20 years of exciting improvements in treatment efficacy outcomes of advanced epidermal growth factor receptor (EGFR) mutant and anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC), also combined with a progressively better safety profile, from chemotherapy to new generation tyrosine kinase inhibitors (TKIs) (osimertinib, alectinib, brigatinib), the recent MARIPOSA and CROWN trials have changed this trend. For the first time in the history of EGFR and ALK treatments, we must face the issue of being a step behind in terms of toxicity profile. The combination of amivantamab plus lazertinib in EGFR mutant NSCLC, and lorlatinib in ALK rearranged NSCLC, has improved efficacy outcomes as never before. The story would be easy and totally positive if these two innovative, amazing treatments were not associated with new peculiar features in safety profiles that must be discussed with patients, because they potentially affect their quality of life. When treating these patient populations, the peculiar safety profiles of amivantamab plu lazertinib and lorlatinib require a well-structured shared decision making, “where and when”, both the high probability of a longer survival and the risk of worse quality of life must be well announced and explained to our patients before the shared final treatment choice.
Keywords
Non-small cell lung cancer; shared-decision making; amivantamab; lorlatinib; osimertinib; alectinib; brigatinib
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