The Impact of EGFR Mutation Status and Brain Metastasis for Non-Small Cell Lung Cancer Treated with Ramucirumab plus Docetaxel

被引:7
作者
Furuya, Naoki [1 ]
Ito, Kentaro [2 ]
Sakaguchi, Tadashi [1 ,2 ]
Hida, Naoya [3 ]
Kakinuma, Kazutaka [1 ]
Morikawa, Kei [1 ]
Inoue, Takeo [1 ]
Komase, Yuko [3 ]
Hataji, Osamu [2 ]
Mineshita, Masamichi [1 ]
机构
[1] St Marianna Univ, Div Resp Med, Dept Internal Med, Sch Med, Kawasaki, Kanagawa, Japan
[2] Matsusaka Municipal Hosp, Resp Ctr, Matsusaka, Japan
[3] St Marianna Univ, Div Resp Med, Yokohama City Seibu Hosp, Sch Med, Yokohama, Kanagawa, Japan
关键词
Non-small cell lung cancer; Ramucirumab; Docetaxel; EGFRmutation; Brain metastasis; CHEMOTHERAPY; GROWTH; TRIAL; REVEL; VEGF;
D O I
10.1159/000507050
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objectives:Currently, combination therapy of ramucirumab (RAM) + docetaxel (DOC) must play a more important role as a second-line treatment. Epithelial growth factor receptor (EGFR) mutation accounts for around 50% of oncogenic driver mutations in patients with advanced non-small cell lung cancer (NSCLC) in Asian subsets. The number of brain metastases (BM) is relatively higher in EGFR mutation-positive patients compared to EGFR wild-type patients. The objective of this study is to evaluate the efficacy of RAM + DOC focusing on EGFR mutation and BM.Methods:We retrospectively reviewed consecutive advanced NSCLC patients who received combination therapy of RAM + DOC at three institutions. A total of 112 patients with NSCLC were enrolled for efficacy analyses. We evaluated the efficacy of RAM + DOC for EGFR-mutated NSCLC with endpoints including progression-free survival (PFS), time to treatment failure (TTF) and overall survival.Results:Median PFS was 5.7 months for the EGFR mutant group compared with 3.6 months for the EGFR wild-type group (HR 0.53, 95% CI 0.32-0.87;p= 0.01). Median TTF was 5.1 months for the EGFR mutant group compared with 2.8 months for the EGFR wild-type group (HR 0.53, 95% CI 0.33-0.85;p= 0.007). Median PFS and TTF of the EGFR mutant group was significantly longer than median PFS and TTF of the EGFR wild-type group. The multivariate analysis identified EGFR mutation status as an independent favorable factor of PFS. In subset analyses of BM, median PFS of the EGFR mutant group (2.8 months) was significantly shorter than that of the EGFR wild-type group (5.1 months) (HR 7.27, 95% CI 1.78-29.68;p= 0.002).Conclusion:This study revealed that EGFR mutation status and BM might be predictive or prognostic factors for PFS.
引用
收藏
页码:661 / 668
页数:8
相关论文
共 25 条
[1]  
Cancer Genome Atlas Research Network, 2018, Nature, V559, pE12, DOI [10.1038/nature13385, 10.1038/s41586-018-0228-6]
[2]   Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer [J].
Gandhi, L. ;
Rodriguez-Abreu, D. ;
Gadgeel, S. ;
Esteban, E. ;
Felip, E. ;
De Angelis, F. ;
Domine, M. ;
Clingan, P. ;
Hochmair, M. J. ;
Powell, S. F. ;
Cheng, S. Y. -S. ;
Bischoff, H. G. ;
Peled, N. ;
Grossi, F. ;
Jennens, R. R. ;
Reck, M. ;
Hui, R. ;
Garon, E. B. ;
Boyer, M. ;
Rubio-Viqueira, B. ;
Novello, S. ;
Kurata, T. ;
Gray, J. E. ;
Vida, J. ;
Wei, Z. ;
Yang, J. ;
Raftopoulos, H. ;
Pietanza, M. C. ;
Garassino, M. C. .
NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (22) :2078-2092
[3]   Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial [J].
Garon, Edward B. ;
Ciuleanu, Tudor-Eliade ;
Arrieta, Oscar ;
Prabhash, Kumar ;
Syrigos, Konstantinos N. ;
Goksel, Tuncay ;
Park, Keunchil ;
Gorbunova, Vera ;
Dario Kowalyszyn, Ruben ;
Pikiel, Joanna ;
Czyzewicz, Grzegorz ;
Orlov, Sergey V. ;
Lewanski, Conrad R. ;
Thomas, Michael ;
Bidoli, Paolo ;
Dakhil, Shaker ;
Gans, Steven ;
Kim, Joo-Hang ;
Grigorescu, Alexandru ;
Karaseva, Nina ;
Reck, Martin ;
Cappuzzo, Federico ;
Alexandris, Ekaterine ;
Sashegyi, Andreas ;
Yurasov, Sergey ;
Perol, Maurice .
LANCET, 2014, 384 (9944) :665-673
[4]   Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis [J].
Hicklin, DJ ;
Ellis, LM .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (05) :1011-1027
[5]   Impact of Epidermal Growth Factor Receptor Mutation on Clinical Outcomes of Nintedanib Plus Docetaxel in Patients with Previously Treated Non-Small Cell Lung Cancer from the Korean Named Patient Program [J].
Hong, Sook-Hee ;
An, Ho Jung ;
Kim, Kihyun ;
Lee, Seung Sei ;
Lee, Yun-Gyoo ;
Yuh, Young-Jin ;
Park, Cheon ;
Chae, Yee Soo ;
Jang, Tae-Won ;
Kang, Jin-Hyoung .
ONCOLOGY, 2019, 96 (01) :51-58
[6]   EGFR mutation status on brain metastases from non-small cell lung cancer [J].
Hsu, Fred ;
De Caluwe, Alex ;
Anderson, David ;
Nichol, Alan ;
Toriumi, Ted ;
Ho, Cheryl .
LUNG CANCER, 2016, 96 :101-107
[7]   Autocrine VEGF Signaling Synergizes with EGFR in Tumor Cells to Promote Epithelial Cancer Development [J].
Lichtenberger, Beate M. ;
Tan, Poi Kiang ;
Niederleithner, Heide ;
Ferrara, Napoleone ;
Petzelbauer, Peter ;
Sibilia, Maria .
CELL, 2010, 140 (02) :268-279
[8]   Gefitinib or Chemotherapy for Non-Small-Cell Lung Cancer with Mutated EGFR. [J].
Maemondo, Makoto ;
Inoue, Akira ;
Kobayashi, Kunihiko ;
Sugawara, Shunichi ;
Oizumi, Satoshi ;
Isobe, Hiroshi ;
Gemma, Akihiko ;
Harada, Masao ;
Yoshizawa, Hirohisa ;
Kinoshita, Ichiro ;
Fujita, Yuka ;
Okinaga, Shoji ;
Hirano, Haruto ;
Yoshimori, Kozo ;
Harada, Toshiyuki ;
Ogura, Takashi ;
Ando, Masahiro ;
Miyazawa, Hitoshi ;
Tanaka, Tomoaki ;
Saijo, Yasuo ;
Hagiwara, Koichi ;
Morita, Satoshi ;
Nukiwa, Toshihiro .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 362 (25) :2380-2388
[9]   Management of Brain Metastases in Tyrosine Kinase Inhibitor-Naive Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer: A Retrospective Multi-Institutional Analysis [J].
Magnuson, William J. ;
Lester-Coll, Nataniel H. ;
Wu, Abraham J. ;
Yang, T. Jonathan ;
Lockney, Natalie A. ;
Gerber, Naamit K. ;
Beal, Kathryn ;
Amini, Arya ;
Patil, Tejas ;
Kavanagh, Brian D. ;
Camidge, D. Ross ;
Braunstein, Steven E. ;
Boreta, Lauren C. ;
Balasubramanian, Suresh K. ;
Ahluwalia, Manmeet S. ;
Rana, Niteshkumar G. ;
Attia, Albert ;
Gettinger, Scott N. ;
Contessa, Joseph N. ;
Yu, James B. ;
Chiang, Veronica L. .
JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (10) :1070-+
[10]   Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial [J].
Mitsudomi, Tetsuya ;
Morita, Satoshi ;
Yatabe, Yasushi ;
Negoro, Shunichi ;
Okamoto, Isamu ;
Tsurutani, Junji ;
Seto, Takashi ;
Satouchi, Miyako ;
Tada, Hirohito ;
Hirashima, Tomonori ;
Asami, Kazuhiro ;
Katakami, Nobuyuki ;
Takada, Minoru ;
Yoshioka, Hiroshige ;
Shibata, Kazuhiko ;
Kudoh, Shinzoh ;
Shimizu, Eiji ;
Saito, Hiroshi ;
Toyooka, Shinichi ;
Nakagawa, Kazuhiko ;
Fukuoka, Masahiro .
LANCET ONCOLOGY, 2010, 11 (02) :121-128