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. 2019 Apr;11(4):1347-1354.
doi: 10.21037/jtd.2019.03.61.

Difference in central nerve system metastasis during gefitinib or erlotinib therapy in patients with EGFR-mutated non-small cell lung cancer: a retrospective study

Kazushi Yoshida  1 , Shintaro Kanda  1 , Hideaki Shiraishi  1 , Keiko Goto  1 , Kota Itahashi  1 , Yasushi Goto  1 , Hidehito Horinouchi  1 , Yutaka Fujiwara  1 , Hiroshi Nokihara  1 , Noboru Yamamoto  1 , Yuichiro Ohe  1
Affiliations

Difference in central nerve system metastasis during gefitinib or erlotinib therapy in patients with EGFR-mutated non-small cell lung cancer: a retrospective study

Kazushi Yoshida et al. J Thorac Dis. 2019 Apr.

Abstract

Background: Central nervous system (CNS) metastasis is a poor prognostic factor in patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation EGFR-mutant NSCLC and is associated with a deteriorated quality of life (QOL). Some clinical studies have suggested a possible difference in the incidence of CNS metastasis between EGFR-mutant NSCLC patients treated with gefitinib and erlotinib, both of which are classified as first-generation EGFR tyrosine kinase inhibitors (TKIs). However, the difference in the incidence of CNS metastasis between patients receiving these two drugs has not yet been sufficiently well investigated. We analyzed the frequency of occurrence/progression of CNS metastasis in EGFR-mutant NSCLC patients treated with erlotinib and gefitinib as the first-line treatment.

Methods: We analyzed the incidence of CNS metastasis, frequency of progression of CNS metastasis and the treatment outcomes in EGFR-mutant patients who received gefitinib or erlotinib as the first-line EGFR-TKI treatment. CNS progressive disease (PD) was defined as progression of CNS metastasis during EGFR-TKI treatment. We also evaluated the progression-free survival (PFS), CNS-PFS, and overall survival (OS) of the patients who received each of the two drugs.

Results: A total of 170 patients were enrolled in the study, of which 144 had received gefitinib, and 26 had received erlotinib. The frequency of CNS PD in the erlotinib group tended to be lower than that in the gefitinib group (11.5% vs. 29.9%, P=0.06). In patients with no existing CNS metastasis at the start of the EGFR-TKI treatments, the incidence of CNS PD was significantly lower in the erlotinib group than that in the gefitinib group (4.8% vs. 24.5%, P=0.04). A re-biopsy after failure of EGFR-TKI treatment was performed in 48 patients. The incidence of EGFR T790M tended to be higher among patients with CNS PD than in those without CNS PD, although the difference was not statistically significant (66.7% vs. 40.4%; P=0.23).

Conclusions: The incidence of progression of CNS metastasis during erlotinib treatment was lower than that during gefitinib treatment. In addition, the difference in the incidence in patients without existing CNS metastasis at the time of start of EGFR-TKI treatment was significantly lower in the patients treated with erlotinib than in those treated with gefitinib.

Keywords: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI); central nervous system (CNS) metastasis; non-small cell lung cancer (NSCLC).

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Conflict of interest statement

Conflicts of Interest: S Kanda received research funding from AstraZeneca, Ono Pharmaceutical and AbbVie, and honoraria from AstraZeneca, Ono Pharmaceutical, Bristol-Myers Squibb, and Chugai. Y Goto has held consulting/advisory roles for Eli Lilly, Chugai, Taiho Pharmaceutical, Boehringer Ingelheim, Pfizer and Novartis, served on the speakers’ bureaus for AstraZeneca, Eli Lilly, Chugai, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, Bristol-Myers Squibb, Pfizer, MSD, Shionogi Pharma and Novartis, and received research funding from AbbVie, Eli Lilly, Taiho Pharmaceutical, Bristol-Myers Squibb and Ono Pharmaceutical. H Horinouchi has received research funding from Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Genomic Health, Merck Serono, MSD, Novartis, Ono Pharmaceutical and Taiho Pharmaceutical, and received honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Eli Lilly, Kyowa Hakko Kirin, MSD, Novartis, Ono Pharmaceutical and Taiho Pharmaceutical. Y Fujiwara has received research funding from AbbVie, AstraZeneca, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Incyte, Merck Serono, MSD and Novartis, served on the speakers’ bureaus from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Ono Pharmaceutical, Taiho Pharmaceutical and Sysmex, and held consulting/advisory roles for AstraZeneca, Bristol-Myers Squibb, Novartis and Ono Pharmaceutical. H Nokihara has received research finding form Merck Serono, Pfizer, Taiho Pharmaceutical, Eisai, Chugai, Eli Lilly, Novartis, Daiichi Sankyo, GlaxoSmithKline, Yakult, Quintiles, Astellas Pharma, AstraZeneca, Boehringer Ingelheim and Ono Pharmaceutical, and received honoraria from AstraZeneca, Ono Pharmaceutical, Eli Lilly, Bristol-Myers Squibb and Chugai. N Yamamoto has received research funding from Astellas, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Janssen pharmaceutical, Kyowa Hakko Kirin, Novartis, Ono Pharmaceutical, Pfizer, Quintiles, Taiho Pharmaceutical, and Takeda; and served on speakers' bureaus from AstraZeneca, Bristol-Myers Squibb, Chugai, Eli Lilly, Ono Pharmaceutical and Pfizer, and held consulting/advisory roles for Boehringer Ingelheim, Cimic, Eisai, OncoTherapy Science, Otsuka, and Takeda. Y Ohe has received research funding from AstraZeneca, Bristol-Myers Squibb, Chugai, Dainippon-Sumitomo, Eli Lilly, Ignyta, Kyorin, MSD, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical and Takeda, and received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Eli Lilly, Kyorin, MSD, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical and Takeda. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
PFS and OS between CNS PD-negative group vs. CNS PD-positive group. CNS, central nervous system; PD, progressive disease; PFS, progression free survival; OS, overall survival.
Figure 2
Figure 2
PFS and OS between gefitinib and erlotinib treatment groups. PFS, progression free survival; OS, overall survival.
Figure 3
Figure 3
PFS and OS between gefitinib and erlotinib treatment groups in patients without CNS metastasis before EGFR-TKI treatment. PFS, progression free survival; OS, overall survival; CNS, central nervous system; EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor.
Figure 4
Figure 4
Time to CNS PD between gefitinib and erlotinib treatment groups. NA, not applicable; CNS, central nervous system; PD, progressive disease.
See this image and copyright information in PMC

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