Efficacy and safety of crizotinib plus bevacizumab in ALK/ROS-1/c-MET positive non-small cell lung cancer: an open-label, single-arm, prospective observational study

被引:1
作者
Huang, Ziwei [1 ,2 ]
Xiong, Qi [2 ]
Cui, Zhi [2 ]
Tao, Haitao [2 ]
Zhang, Sujie [2 ]
Wang, Lijie [2 ]
Cui, Pengfei [2 ]
Chen, Shixue [2 ]
Huang, Di [1 ]
Yang, Bo [2 ]
Hu, Yi [2 ]
机构
[1] Nankai Univ, Sch Med, Weijin Rd 94, Tianjin 300071, Peoples R China
[2] Gen Hosp Chinese PLA, Dept Oncol, Fuxing Rd 28, Beijing 100853, Peoples R China
来源
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH | 2021年 / 13卷 / 03期
关键词
Crizotinib; bevacizumab; ALK; ROS-1; c-MET; brain metastasis; GROWTH-FACTOR RECEPTOR; BRAIN METASTASES; VEGF-A; RESISTANCE; SURVIVAL; ANGIOGENESIS; CHEMOTHERAPY; BENEFIT; EGFR;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Crizotinib is a tyrosine kinase inhibitor (TKI) effective in ALK/ROS-1/c-MET positive non-small cell lung cancer (NSCLC) patients. Bevacizumab is an antiangiogenic monoclonal antibody, and improves clinical benefit of NSCLC in combination with EGFR-TKIs or chemotherapy. However, the efficacy and safety of crizotinib plus bevacizumab in treating naive ALK/ROS-1/c-MET positive NSCLC patients have not been studied. Methods: In this open-label, single-arm, prospective observational study, locally advanced or metastatic ALK rearrangement/ROS-1 fusion/c-MET amplification NSCLC patients were treated with crizotinib (250 mg orally twice daily) and bevacizumab (7.5 mg/kg intravenous every three weeks) until disease progression or intolerant toxicity or death. Primary end point was progressive free survival (PFS), secondary end points were duration of response (DOR), overall response rate (ORR), disease control rate (DCR) and safety. Patients receiving >= 1 cycle of treatment were evaluated. Findings: Fourteen patients were eligible for analyzing between June 2016 and October 2017. There were 12 patients with ALK rearrangement, 1 patient with ROS-1 fusion, and 1 patient with c-MET amplification. The median follow-up time was 42.8 months. The median PFS and DOR of the patients with ALK rearrangement were 13.9 and 14.8 months respectively. Of the 12 patients, 7 gained partial response, 5 gained stable disease. The ORR and DCR were 58.3% and 100%. The PFS were 12.9 months and 1.9 months for patient with ROS-1 fusion or c-MET amplification. The most two common treatment-related adverse events were fatigue (28.6%) and rash (21.4%). 3 patients discontinued therapy because of liver damage or hemoptysis. Interpretation: This study demonstrated that crizotinib plus bevacizumab showed benefit in treating naive ALK rearrangement NSCLC patients, and the toxicity was relatively tolerant. Our results suggested that crizotinib plus bevacizumab might be a promising treatment strategy in ALK/ ROS-1/c-MET positive NSCLC patients.
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收藏
页码:1526 / 1534
页数:9
相关论文
共 35 条
[1]   Nonsmall cell lung carcinoma: diagnostic difficulties in small biopsies and cytological specimens [J].
Bubendorf, Lukas ;
Lantuejoul, Sylvie ;
de langen, Adrianus J. ;
Thunnissen, Erik .
EUROPEAN RESPIRATORY REVIEW, 2017, 26 (144)
[2]   Efficacy and safety of crizotinib in patients with advanced c-MET-amplified non-small cell lung cancer (NSCLC) [J].
Camidge, D. Ross ;
Ou, Sai-Hong Ignatius ;
Shapiro, Geoffrey ;
Otterson, Gregory Alan ;
Villaruz, Liza Cosca ;
Villalona-Calero, Miguel Angel ;
Iafrate, A. John ;
Varella-Garcia, Marileila ;
Dacic, Sanja ;
Cardarella, Stephanie ;
Zhao, Weiqiang ;
Tye, Lesley ;
Stephenson, Patricia ;
Wilner, Keith D. ;
James, Leonard Philip ;
Socinski, Mark A. .
JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (15)
[3]   Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor-resistant human lung adenocarcinoma [J].
Cascone, Tina ;
Herynk, Matthew H. ;
Xu, Li ;
Du, Zhiqiang ;
Kadara, Humam ;
Nilsson, Monique B. ;
Oborn, Carol J. ;
Park, Yun-Yong ;
Erez, Baruch ;
Jacoby, Joerg J. ;
Lee, Ju-Seog ;
Lin, Heather Y. ;
Ciardiello, Fortunato ;
Herbst, Roy S. ;
Langley, Robert R. ;
Heymach, John V. .
JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (04) :1313-1328
[4]   Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer [J].
Choi, Young Lim ;
Takeuchi, Kengo ;
Soda, Manabu ;
Inamura, Kentaro ;
Togashi, Yuki ;
Hatano, Satoko ;
Enomoto, Munehiro ;
Hamada, Toru ;
Haruta, Hidenori ;
Watanabe, Hideki ;
Kurashina, Kentaro ;
Hatanaka, Hisashi ;
Ueno, Toshihide ;
Takada, Shuji ;
Yamashita, Yoshihiro ;
Sugiyama, Yukihiko ;
Ishikawa, Yuichi ;
Mano, Hiroyuki .
CANCER RESEARCH, 2008, 68 (13) :4971-4976
[5]   Clinical Experience With Crizotinib in Patients With Advanced ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastases [J].
Costa, Daniel B. ;
Shaw, Alice T. ;
Ou, Sai-Hong I. ;
Solomon, Benjamin J. ;
Riely, Gregory J. ;
Ahn, Myung-Ju ;
Zhou, Caicun ;
Shreeve, S. Martin ;
Selaru, Paulina ;
Polli, Anna ;
Schnell, Patrick ;
Wilner, Keith D. ;
Wiltshire, Robin ;
Camidge, D. Ross ;
Crino, Lucio .
JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (17) :1881-1888
[6]   Crizotinib resistance: implications for therapeutic strategies [J].
Dagogo-Jack, I. ;
Shaw, A. T. .
ANNALS OF ONCOLOGY, 2016, 27 :42-50
[7]   Epidermal growth factor receptor in tumor angiogenesis [J].
Ellis, LM .
HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA, 2004, 18 (05) :1007-+
[8]   Non Small Cell Lung Cancer [J].
Ettinger, David S. ;
Akerley, Wallace ;
Bepler, Gerold ;
Blum, Matthew G. ;
Chang, Andrew ;
Cheney, Richard T. ;
Chirieac, Lucian R. ;
D'Amico, Thomas A. ;
Demmy, Todd L. ;
Ganti, Apar Kishor P. ;
Govindan, Ramaswamy ;
Grannis, Frederic W., Jr. ;
Jahan, Thierry ;
Jahanzeb, Mohammad ;
Johnson, David H. ;
Kessinger, Anne ;
Komaki, Ritsuko ;
Kong, Feng-Ming ;
Kris, Mark G. ;
Krug, Lee M. ;
Le, Quynh-Thu ;
Lennes, Inga T. ;
Martins, Renato ;
O'Malley, Janis ;
Osarogiagbon, Raymond U. ;
Otterson, Gregory A. ;
Patel, Jyoti D. ;
Pisters, Katherine M. ;
Reckamp, Karen ;
Riely, Gregory J. ;
Rohren, Eric ;
Simon, George R. ;
Swanson, Scott J. ;
Wood, Douglas E. ;
Yang, Stephen C. .
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK, 2010, 8 (07) :740-+
[9]   VEGF-A: a critical regulator of blood vessel growth [J].
Ferrara, Napoleone .
EUROPEAN CYTOKINE NETWORK, 2009, 20 (04) :158-163
[10]   Bevacizumab Prevents Brain Metastases Formation in Lung Adenocarcinoma [J].
Ilhan-Mutlu, Ayseguel ;
Osswald, Matthias ;
Liao, Yunxiang ;
Goemmel, Miriam ;
Reck, Martin ;
Miles, David ;
Mariani, Paola ;
Gianni, Luca ;
Lutiger, Beatrix ;
Nendel, Viktor ;
Srock, Stefanie ;
Perez-Moreno, Pablo ;
Thorsen, Frits ;
von Baumgarten, Louisa ;
Preusser, Matthias ;
Wick, Wolfgang ;
Winkler, Frank .
MOLECULAR CANCER THERAPEUTICS, 2016, 15 (04) :702-710