Erlotinib and bevacizumab in elderly patients ≥75 years old with non-small cell lung cancer harboring epidermal growth factor receptor mutations

被引:7
作者
Aoshima, Yoichiro [1 ]
Karayama, Masato [1 ,2 ]
Inui, Naoki [1 ,3 ]
Yasui, Hideki [1 ]
Hozumi, Hironao [1 ]
Suzuki, Yuzo [1 ]
Furuhashi, Kazuki [1 ]
Fujisawa, Tomoyuki [1 ]
Enomoto, Noriyuki [1 ]
Nakamura, Yutaro [1 ]
Mikamo, Masashi [4 ]
Matsuura, Shun [5 ]
Kusagaya, Hideki [6 ]
Kaida, Yusuke [7 ]
Uto, Tomohiro [8 ]
Hashimoto, Dai [9 ]
Matsui, Takashi [10 ]
Asada, Kazuhiro [11 ]
Suda, Takafumi [1 ]
机构
[1] Hamamatsu Univ, Dept Internal Med, Sch Med, Div 2, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan
[2] Hamamatsu Univ, Dept Clin Oncol, Sch Med, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan
[3] Hamamatsu Univ, Dept Clin Pharmacol & Therapeut, Sch Med, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan
[4] Hamamatsu Med Ctr, Dept Resp Med, 328 Tomitsuka, Hamamatsu, Shizuoka 4328580, Japan
[5] Fujieda Municipal Gen Hosp, Dept Resp Med, 4-1-11 Surugadai, Fujieda, Shizuoka 4268677, Japan
[6] Shizuoka Saiseikai Hosp, Dept Resp Med, 1-1-1 Oshika, Shizuoka 4228527, Japan
[7] Ensyu Hosp, Dept Resp Med, 1-1-1 Chuou, Hamamatsu, Shizuoka 4300929, Japan
[8] Iwata City Hosp, Dept Resp Med, 513-2 Ohkubo, Iwata 4388550, Japan
[9] Seirei Hamamatsu Gen Hosp, Dept Resp Med, 2-12-12 Sumiyoshi, Hamamatsu, Shizuoka 4308558, Japan
[10] Seirei Mikatahara Gen Hosp, Dept Resp Med, 3453 Mikatahara Cho, Hamamatsu, Shizuoka 4338558, Japan
[11] Shizuoka Prefectural Gen Hosp, Dept Resp Med, 4-27-1 Kita Ando, Shizuoka 4200881, Japan
关键词
Bevacizumab; Elderly patients; Epidermal growth factor receptor mutation; Erlotinib; Targeted therapy; OPEN-LABEL; 1ST-LINE TREATMENT; CHEMOTHERAPY; MULTICENTER; EFFICACY; OSIMERTINIB; CARBOPLATIN; COMBINATION; PACLITAXEL; ANTIBODY;
D O I
10.1007/s10637-020-00988-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The efficacy and safety of combination therapy with erlotinib and bevacizumab in elderly patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) gene mutations are unknown. Elderly patients aged >= 75 years old with advanced or recurrent NSCLC andEGFRmutations (exon 19 deletion or L858R mutation in exon 21) received erlotinib (150 mg, daily) and bevacizumab (15 mg/kg on day 1 of a 21-day cycle) until disease progression or the occurrence of unacceptable toxicities. The primary endpoint was progression-free survival from enrollment. Twenty-five patients were enrolled in this study, and the median age was 80 years. Fifteen (60.0%) and 10 patients (40.0%) had exon 21 L858R mutations and exon 19 deletions, respectively. The median progression-free survival from enrollment was 12.6 months [95% confidence interval (CI): 8.0-33.7 months]. The objective response rate was 88.0% [95% CI: 74.0%-99.0%], and the disease control rate was 100% [95% CI: 88.7%-100%]. Grade 3 or higher adverse events occurred in 12 patients (48.0%), and rash and nausea were the most common. Grade 3 or higher bevacizumab-related toxicities occurred in 4 (16.0%) patients, including proteinuria (n = 2), gastrointestinal perforation (n = 1) and pneumothorax (n = 1). A dose reduction of erlotinib and cessation of bevacizumab was required in 16 (64.0%) and 18 patients (72.0%), respectively. Erlotinib and bevacizumab combination therapy showed a minimal survival benefit with frequent dose reductions and/or treatment discontinuations in elderly patients withEGFR-positive NSCLC.
引用
收藏
页码:210 / 216
页数:7
相关论文
共 29 条
[1]  
[Anonymous], NCCN Clinical Practice Guidelines in Oncology: Breast Cancer
[2]   Revacizumab-induced transient remodeling of the vasculature in neuroblastoma xenografts results in improved delivery and efficacy of systemically administered chemotherapy [J].
Dickson, Paxton V. ;
Hamner, John B. ;
Sims, Thomas L. ;
Fraga, Charles H. ;
Ng, Catherine Y. C. ;
Rajasekeran, Surender ;
Hagedorn, Nikolaus L. ;
McCarville, M. Beth ;
Stewart, Clinton F. ;
Davidoff, Andrew M. .
CLINICAL CANCER RESEARCH, 2007, 13 (13) :3942-3950
[3]   New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) [J].
Eisenhauer, E. A. ;
Therasse, P. ;
Bogaerts, J. ;
Schwartz, L. H. ;
Sargent, D. ;
Ford, R. ;
Dancey, J. ;
Arbuck, S. ;
Gwyther, S. ;
Mooney, M. ;
Rubinstein, L. ;
Shankar, L. ;
Dodd, L. ;
Kaplan, R. ;
Lacombe, D. ;
Verweij, J. .
EUROPEAN JOURNAL OF CANCER, 2009, 45 (02) :228-247
[4]   Aging and cancer: Issues of basic and clinical science [J].
Ershler, WB ;
Longo, DL .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1997, 89 (20) :1489-1497
[5]   Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer [J].
Ferrara, N ;
Hillan, KJ ;
Gerber, HP ;
Novotny, W .
NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (05) :391-400
[6]   Chemotherapy for elderly patients with non-small cell lung cancer - A review of the evidence [J].
Gridelli, C ;
Shepherd, FA .
CHEST, 2005, 128 (02) :947-957
[7]   Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial [J].
Herbst, Roy S. ;
Ansari, Rafat ;
Bustin, Frederique ;
Flynn, Patrick ;
Hart, Lowell ;
Otterson, Gregory A. ;
Vlahovic, Gordana ;
Soh, Chang-Heok ;
O'Connor, Paula ;
Hainsworth, John .
LANCET, 2011, 377 (9780) :1846-1854
[8]   Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study [J].
Hosomi, Yukio ;
Morita, Satoshi ;
Sugawara, Shunichi ;
Kato, Terufumi ;
Fukuhara, Tatsuro ;
Gemma, Akihiko ;
Takahashi, Kazuhisa ;
Fujita, Yuka ;
Harada, Toshiyuki ;
Minato, Koichi ;
Takamura, Kei ;
Hagiwara, Koichi ;
Kobayashi, Kunihiko ;
Nukiwa, Toshihiro ;
Inoue, Akira ;
Kudoh, S. ;
Nagao, K. ;
Nakai, Y. ;
Yoshioka, T. ;
Harada, M. ;
Isobe, T. ;
Kasai, T. ;
Oizumi, S. ;
Kamimura, M. ;
Watanabe, S. ;
Okamoto, H. ;
Shingyoji, M. ;
Osaki, Y. ;
Hasegawa, Y. ;
Koyama, S. ;
Isobe, H. ;
Morikawa, N. ;
Ishida, T. ;
Ishii, Y. ;
Takiguchi, Y. ;
Watanabe, H. ;
Kurokawa, H. ;
Sunaga, N. ;
Mori, Y. ;
Tabata, T. ;
Nakagawa, T. ;
Kuyama, S. ;
Kiura, K. ;
Usui, K. ;
Soejima, K. ;
Nishitsuji, M. ;
Kinoshita, I ;
Taima, K. ;
Nishimura, N. ;
Kishi, K. .
JOURNAL OF CLINICAL ONCOLOGY, 2020, 38 (02) :115-+
[9]   Phase II study of erlotinib in elderly patients with non-small cell lung cancer harboring epidermal growth factor receptor mutations [J].
Inoue, Yusuke ;
Inui, Naoki ;
Asada, Kazuhiro ;
Karayama, Masato ;
Matsuda, Hiroyuki ;
Yokomura, Koshi ;
Koshimizu, Naoki ;
Imokawa, Shiro ;
Yamada, Takashi ;
Shirai, Toshihiro ;
Kasamatsu, Norio ;
Suda, Takafumi .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2015, 76 (01) :155-161
[10]   Investigation of the freely available easy-to-use software 'EZR' for medical statistics [J].
Kanda, Y. .
BONE MARROW TRANSPLANTATION, 2013, 48 (03) :452-458