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. 2019 Jun;11(6):2350-2360.
doi: 10.21037/jtd.2019.06.03.

Impact of clinical features on the efficacy of osimertinib therapy in patients with T790M-positive non-small cell lung cancer and acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors

Yasuhiro Kato  1   2 , Yukio Hosomi  1 , Kageaki Watanabe  1 , Makiko Yomota  1 , Shoko Kawai  1 , Yusuke Okuma  1   3 , Kaoru Kubota  2 , Masahiro Seike  2 , Akihiko Gemma  2 , Tatsuru Okamura  1
Affiliations

Impact of clinical features on the efficacy of osimertinib therapy in patients with T790M-positive non-small cell lung cancer and acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors

Yasuhiro Kato et al. J Thorac Dis. 2019 Jun.

Abstract

Background: Osimertinib exhibits good efficacy in patients with T790M-positive non-small cell lung cancer (NSCLC) and acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). Compared with the clinical trials, in real-world clinical practice, osimertinib must be administered to older patients and those with poor Eastern Cooperative Oncology Group performance status (ECOG-PS). Therefore, we investigated the association between osimertinib efficacy/safety and PS score, age, and other clinical features in patients with T790M-positive NSCLC.

Methods: We reviewed all patients with T790M-positive NSCLC and acquired resistance to initial EGFR-TKIs who were administered osimertinib between March 2016 and January 2018 at the Tokyo Metropolitan Cancer and Infectious Diseases Center in Komagome Hospital, Japan.

Results: In total, 31 patients, including 8 young (<65 years) and 23 elderly (≥65 years) patients, were included in the study. Of these, 10 (32.3%) patients had poor PS scores. The progression-free survival (PFS) was significantly shorter in young patients was than elderly patients [3.5 vs. 6.4 months, P=0.041; hazard ratio (HR), 2.41]. The overall survival (OS) of the young patients tended to be shorter than that of the elderly patients (5.3 vs. 19.4 months, P=0.067; HR, 2.58). The PFS (9.1 vs. 5.5 months; P=0.071; HR, 0.38) and the OS (not reached vs. 6.6 months, P=0.061; HR, 0.39) were shorter in patients with poor ECOG-PS than those with good ECOG-PS. The toxic effects of osimertinib were manageable. By multivariate analysis, both age and ECOG-PS were independent predictors of osimertinib efficacy.

Conclusions: Poor ECOG-PS and younger age were associated with lower efficacy of osimertinib in T790M-positive NSCLC.

Keywords: EGFR-TKI; Lung cancer; Threonine790Methionine; epidermal growth factor receptor (EGFR); osimertinib.

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Conflict of interest statement

Conflicts of Interest: Y Hosomi, Y Okuma, K Kubota, M Seike and A Gemma have received honoraria from AstraZeneca. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Impact of age. Progression-free survival (A) and overall survival (B) of patients with T790M-positive non-small cell lung cancer treated with osimertinib.
Figure 2
Figure 2
Impact of performance status. Progression-free survival (A) and overall survival (B) of patients with T790M-positive non-small cell lung cancer treated with osimertinib.
Figure 3
Figure 3
Univariate analysis of associations between outcomes and clinical features. PFS, progression-free survival; OS, overall survival; CNS, central nervous system.
Figure 4
Figure 4
Multivariate analysis of associations between outcomes and age or performance status. PFS, progression-free survival; OS, overall survival.
See this image and copyright information in PMC

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