TY  - EJOU
AU  - Maione, Paolo 
AU  - Palma, Valentina 
AU  - Gridelli, Cesare 

TI  - Lorlatinib and Amivantamab: A Paradigm Shift in <i>EGFR</i> and <i>ALK</i> Positive NSCLC, with More Effective but More Toxic Treatments Requiring a Well-Structured Shared Decision Making
T2  - Oncology Research

PY  - 2026
VL  - 34
IS  - 4
SN  - 1555-3906

AB  - After about 20 years of exciting improvements in treatment efficacy outcomes of advanced epidermal growth factor receptor (<i>EGFR</i>) mutant and anaplastic lymphoma kinase (<i>ALK</i>) 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 <i>EGFR</i> and <i>ALK</i> treatments, we must face the issue of being a step behind in terms of toxicity profile. The combination of amivantamab plus lazertinib in <i>EGFR</i> mutant NSCLC, and lorlatinib in <i>ALK</i> 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.
KW  - Non-small cell lung cancer; shared-decision making; amivantamab; lorlatinib; osimertinib; alectinib; brigatinib

DO  - 10.32604/or.2026.072992