Research Perspectives:

From osimertinib to preemptive combinations

Mikhail V. Blagosklonny _

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Oncotarget. 2024; 15:232-237. https://doi.org/10.18632/oncotarget.28569

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Mikhail V. Blagosklonny1

1 Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA

Correspondence to:

Mikhail V. Blagosklonny, email: [email protected],
[email protected]

Keywords: lung cancer; NSCLC; EGFR; resistance; afatinib; gefitinib; capmatinib

Received: February 23, 2024     Accepted: March 11, 2024     Published: March 15, 2024

Copyright: © 2024 Blagosklonny. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Here, I suggest that while first-line osimertinib extends median progression-free survival (PFS) in EGFR-mutant lung cancer compared to first-generation TKIs, it reduces individual PFS in 15–20% of patients compared to first-generation TKIs. Since detecting a single resistant cell before treatment is usually impossible, osimertinib must be used in all patients as a first-line treatment, raising median PFS overall but harming some. The simplest remedy is a preemptive combination (PC) of osimertinib and gefitinib. A comprehensive PC (osimertinib, afatinib/gefitinib, and capmatinib) could dramatically increase PFS for 80% of patients compared to osimertinib alone, without harming anyone. This article also explores PCs for MET-driven lung cancer.

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