Purpose
The phase 3 randomized SQUIRE study revealed significantly longer overall survival (OS) and progression-free survival (PFS) for necitumumab plus gemcitabine and cisplatin (neci+GC) than for gemcitabine and cisplatin alone (GC) in 1,093 patients with previously untreated advanced squamous non-small cell lung cancer (NSCLC). This post hoc subgroup analysis assessed the efficacy and safety of neci+GC among East Asian (EA) patients enrolled in the study.
Materials and Methods
All patients received up to six 3-week cycles of gemcitabine (days 1 and 8, 1,250 mg/m²) and cisplatin (day 1, 75 mg/m²). Patients in the neci+GC arm also received necitumumab (days 1 and 8, 800 mg) until disease progression or unacceptable toxicity. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from stratified Cox proportional hazards models.
Results
In EA patients, there were improvements for neci+GC (n=43) versus GC (n=41) in OS (HR, 0.805; 95% CI, 0.484 to 1.341) and PFS (HR, 0.720; 95% CI, 0.439 to 1.180), consistent with the results for non-EA patients observed in the present study. The overall safety data were consistent between EA and non-EA patients. A numerically higher proportion of patients experienced serious adverse events (AEs), grade ≥ 3 AEs, and AEs with an outcome of death for neci+GC versus GC in EA patients and EA patients versus non-EA patients for neci+GC.
Conclusion
Although limited by the small sample size and post hoc nature of the analysis, these findings are consistent with those of the overall study and suggest that neci+GC offers a survival advantage and favorable benefit/risk for EA patients with advanced squamous NSCLC.
Citations
Citations to this article as recorded by
Phytochemicals intended for anticancer effects at preclinical levels to clinical practice: Assessment of formulations at nanoscale for non-small cell lung cancer (NSCLC) therapy The Hong Phong Nguyen, V. Bharath Kumar, Vinoth Kumar Ponnusamy, Thi Thu Thao Mai, Phuong Tran Nhat, Kathirvel Brindhadevi, Arivalagan Pugazhendhi Process Biochemistry.2021; 104: 55. CrossRef
Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis Irena Ilic, Sandra Sipetic, Jovan Grujicic, Milena Ilic Journal of Oncology Pharmacy Practice.2020; 26(6): 1331. CrossRef
Recent progress in systemic treatment for lung cancer Jeffrey W. Clark, Dan L. Longo Current Opinion in Pulmonary Medicine.2018; 24(4): 355. CrossRef
Necitumumab in the treatment of non-small-cell lung cancer: clinical controversies Vincenzo di Noia, Ettore D’Argento, Sara Pilotto, Giulia Grizzi, Mario Caccese, Roberto Iacovelli, Giampaolo Tortora, Emilio Bria Expert Opinion on Biological Therapy.2018; 18(9): 937. CrossRef
SELECT-3: a phase I study of selumetinib in combination with platinum-doublet chemotherapy for advanced NSCLC in the first-line setting Alastair Greystoke, Nicola Steele, Hendrik-Tobias Arkenau, Fiona Blackhall, Noor Md Haris, Colin R Lindsay, Raffaele Califano, Mark Voskoboynik, Yvonne Summers, Karen So, Dana Ghiorghiu, Angela W Dymond, Stuart Hossack, Ruth Plummer, Emma Dean British Journal of Cancer.2017; 117(7): 938. CrossRef
Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.
Citations
Citations to this article as recorded by
The Potential Impact of Renin–Angiotensin System Inhibitors on Cancer Survival and Recurrence: A Systemic Review and Meta-Analysis Kaneez Fatima, Aayat Ellahi, Mariam Adil, Haider Kashif, Muhammad Uzair, Naela Ashraf, Mehak Barolia, Mujtaba Hyder, Areeba Nakhuda, Michelle Ayub, Sofia Jamil Butt, Ahmed Mustafa Rashid Journal of Cardiovascular Pharmacology.2025; 85(1): 35. CrossRef
Efficacy and Safety of Low-Dose Apatinib Combined with Chemotherapy as Second-Line Treatment for Advanced Gastric Cancer: A Meta-Analysis Liang Wang, Juyuan Li, Huamin Chen Chemotherapy.2024; 69(1): 11. CrossRef
Ononin: A comprehensive review of anticancer potential of natural isoflavone glycoside Ujjawal Sharma, Bunty Sharma, Ambrish Mishra, Anidrisha Sahu, Darin M. Mathkor, Shafiul Haque, Deepika Raina, Seema Ramniwas, Madhu Gupta, Hardeep S. Tuli Journal of Biochemical and Molecular Toxicology.2024;[Epub] CrossRef
Dihydroartemisinin inhibited vasculogenic mimicry in gastric cancer through the FGF2/FGFR1 signaling pathway Huina Wang, Qingzhu Ding, Haihua zhou, Chuanjiang Huang, Guiyuan Liu, Xiaojun Zhao, Zhiyi Cheng, Xiaolan You Phytomedicine.2024; 134: 155962. CrossRef
Randomized phase II study of capecitabine plus cisplatin with or without sorafenib in patients with metastatic gastric cancer (STARGATE) Min‐Hee Ryu, Kyung Hee Lee, Lin Shen, Kun‐Huei Yeh, Changhoon Yoo, Young Seon Hong, Young Iee Park, Sung Hyun Yang, Dong Bok Shin, Dae Young Zang, Won Ki Kang, Ik‐Joo Chung, Yeul Hong Kim, Baek‐Yeol Ryoo, Byung‐Ho Nam, Young Soo Park, Yoon‐Koo Kang Cancer Medicine.2023; 12(7): 7784. CrossRef
Use of ramucirumab for various treatment lines in real-world practice of patients with advanced hepatocellular carcinoma Naoya Kanogawa, Sadahisa Ogasawara, Susumu Maruta, Yotaro Iino, Masamichi Obu, Takamasa Ishino, Keita Ogawa, Sae Yumita, Terunao Iwanaga, Hidemi Unozawa, Miyuki Nakagawa, Kisako Fujiwara, Takafumi Sakuma, Naoto Fujita, Ryuta Kojima, Hiroaki Kanzaki, Keisu BMC Gastroenterology.2023;[Epub] CrossRef
Pazopanib with 5‐FU and oxaliplatin as first line therapy in advanced gastric cancer: A randomized phase‐II study—The PaFLO trial. A study of the Arbeitsgemeinschaft Internistische Onkologie AIO‐STO‐0510 Anica Högner, Salah‐Eddin Al‐Batran, Jens T. Siveke, Mario Lorenz, Prisca Bartels, Kirstin Breithaupt, Peter Malfertheiner, Nils Homann, Alexander Stein, Dietrich Gläser, Ingo Tamm, Axel Hinke, Arndt Vogel, Peter Thuss‐Patience International Journal of Cancer.2022; 150(6): 1007. CrossRef
Diagnostic value of combined prealbumin-to-fibrinogen and albumin-to-fibrinogen ratios in Hp-negative gastric cancer Linyan Zhang, Simeng Qin, Liuyi Lu, Li Huang, Shan Li The International Journal of Biological Markers.2022; 37(1): 66. CrossRef
Tumor vessel normalization and immunotherapy in gastric cancer Xianzhe Yu, Shan He, Jian Shen, Qiushi Huang, Peng Yang, Lin Huang, Dan Pu, Li Wang, Lu Li, Jinghua Liu, Zelong Liu, Lingling Zhu Therapeutic Advances in Medical Oncology.2022;[Epub] CrossRef
Pull the plug: Anti‐angiogenesis potential of natural products in gastrointestinal cancer therapy Yanling Ai, Ziyi Zhao, Hengyi Wang, Xiaomei Zhang, Weihan Qin, Yanlei Guo, Maoyuan Zhao, Jianyuan Tang, Xiao Ma, Jinhao Zeng Phytotherapy Research.2022; 36(9): 3371. CrossRef
Selenium substituted axitinib reduces axitinib side effects and maintains its anti-renal tumor activity Ying Fu, Rengui Saxu, Kadir Ahmad Ridwan, Cai Zhao, Xiangshun Kong, Yao Rong, Weida Zheng, Peng Yu, Yuou Teng RSC Advances.2022; 12(34): 21821. CrossRef
Ferulic Acid: A Natural Phenol That Inhibits Neoplastic Events through Modulation of Oncogenic Signaling Hardeep Singh Tuli, Ajay Kumar, Seema Ramniwas, Renuka Coudhary, Diwakar Aggarwal, Manoj Kumar, Ujjawal Sharma, Nidarshana Chaturvedi Parashar, Shafiul Haque, Katrin Sak Molecules.2022; 27(21): 7653. CrossRef
Upregulation of Linc-ROR Promotes the Proliferation, Migration, and Invasion of Gastric Cancer Cells Through miR-212-3p/FGF7 Axis Yanjun Mi, Yongwen Li, Zhuo He, Donghan Chen, Qingqi Hong, Jun You Cancer Management and Research.2021; Volume 13: 899. CrossRef
Autophagy inhibitor potentiates the antitumor efficacy of apatinib in uterine sarcoma by stimulating PI3K/Akt/mTOR pathway Shucheng Chen, Lan Yao Cancer Chemotherapy and Pharmacology.2021; 88(2): 323. CrossRef
Combined detection of peripheral blood VEGF and inflammation biomarkers to evaluate the clinical response and prognostic prediction of non-operative ESCC Yuanyuan Ma, Xinyu Su, Xin Li, Xiaohui Zhi, Kan Jiang, Jianhong Xia, Hongliang Li, Chen Yan, Liqing Zhou Scientific Reports.2021;[Epub] CrossRef
Tenascin-c knockdown suppresses vasculogenic mimicry of gastric cancer by inhibiting ERK- triggered EMT Xing Kang, En Xu, Xingzhou Wang, Lulu Qian, Zhi Yang, Heng Yu, Chao Wang, Chuanfu Ren, Yizhou Wang, Xiaofeng Lu, Xuefeng Xia, Wenxian Guan, Tong Qiao Cell Death & Disease.2021;[Epub] CrossRef
A novel role for apatinib in enhancing radiosensitivity in non-small cell lung cancer cells by suppressing the AKT and ERK pathways Lin Li, Yuexian Li, Huawei Zou PeerJ.2021; 9: e12356. CrossRef
Ramucirumab after prior sorafenib in patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein: Japanese subgroup analysis of the REACH-2 trial Masatoshi Kudo, Takuji Okusaka, Kenta Motomura, Izumi Ohno, Manabu Morimoto, Satoru Seo, Yoshiyuki Wada, Shinpei Sato, Tatsuya Yamashita, Masayuki Furukawa, Takeshi Aramaki, Seijin Nadano, Kazuyoshi Ohkawa, Hirofumi Fujii, Toshihiro Kudo, Junji Furuse, Hi Journal of Gastroenterology.2020; 55(6): 627. CrossRef
The Correlation between EGFR and Androgen Receptor Pathways: A Novel Potential Prognostic Marker in Gastric Cancer Shahrzad S. Fard, Kioomars Saliminejad, Masoud Sotoudeh, Niloofar Soleimanifard, Shaghayegh Kouchaki, Mansour Yazdanbod, Habibollah Mahmoodzadeh, Ardeshir Ghavamzadeh, Reza Malekzadeh, Bahram Chahardouli, Kamran Alimoghaddam, Seyed H. Ghaffari Anti-Cancer Agents in Medicinal Chemistry.2020; 19(17): 2097. CrossRef
Third- and later-line treatment in advanced or metastatic gastric cancer: a systematic review and meta-analysis Alessandro Rizzo, Veronica Mollica, Angela Dalia Ricci, Ilaria Maggio, Maria Massucci, Fabiola Lorena Rojas Limpe, Francesca Di Fabio, Andrea Ardizzoni Future Oncology.2020; 16(2): 4409. CrossRef
S-1 plus apatinib as first-line palliative treatment for stage IVB gastroesophageal junction adenocarcinoma Chu Zhang, Guang-Mao Yu, Miao Zhang, Dong Liu Medicine.2020; 99(1): e18691. CrossRef
An open label, multicenter, noninterventional study of apatinib in advanced gastric cancer patients (AHEAD-G202) Xiang Wang, Ruixing Zhang, Nan Du, Mudan Yang, Aimin Zang, Likun Liu, Junyan Yu, Jinghua Gao, Junping Zhang, Zhanzhao Fu, Yuchuan Ren, Liwen Ma, Jun Guo, Qingshan Li, Xiaomei Li, Zaiwen Fan, Xiang Song, Zheng Liu, Yan Zhang, Guozhong Li, Zhonghe Yu, Jianf Therapeutic Advances in Medical Oncology.2020;[Epub] CrossRef
The efficacy and safety of Apatinib mesylate in the treatment of metastatic osteosarcoma patients who progressed after standard therapy and the VEGFR2 gene polymorphism analysis Jia-Yong Liu, Bao-Rang Zhu, Yu-Dong Wang, Xin Sun International Journal of Clinical Oncology.2020; 25(6): 1195. CrossRef
Clinical efficacy and safety of apatinib as maintenance treatment in patients with advanced esophageal squamous cell carcinoma Guohui Liu, Yanbo Wang, Chunbo Wang, Yunlong He, Mingyan E Expert Review of Clinical Pharmacology.2020; 13(12): 1423. CrossRef
Effective Treatment of Cytotoxic Agent Refractory Alpha-Fetoprotein-Producing Gastric Cancer with Ramucirumab: a Case Report and Review of the Literature Jun Takada, Hiroshi Araki, Noritaka Ozawa, Tomohiko Sugiyama, Masaya Kubota, Takashi Ibuka, Masahito Shimizu Journal of Gastrointestinal Cancer.2019; 50(3): 556. CrossRef
Pazopanib Monotherapy Is Active in Relapsed and Refractory Metastatic Gastroesophageal Adenocarcinoma and Can Produce Durable Response Vineet Govinda Gupta, Ranga Rao Rangaraju, Rajat Saha, Peush Bajpai Journal of Gastrointestinal Cancer.2019; 50(4): 943. CrossRef
Safety and Tolerability of Anti-Angiogenic Protein Kinase Inhibitors and Vascular-Disrupting Agents in Cancer: Focus on Gastrointestinal Malignancies Letizia Procaccio, Vera Damuzzo, Francesca Di Sarra, Alberto Russi, Federica Todino, Vincenzo Dadduzio, Francesca Bergamo, Alessandra Anna Prete, Sara Lonardi, Hans Prenen, Angelo Claudio Palozzo, Fotios Loupakis Drug Safety.2019; 42(2): 159. CrossRef
VEGFR2 promotes tumorigenesis and metastasis in a pro-angiogenic-independent way in gastric cancer Lian Lian, Xiang-Li Li, Meng-Dan Xu, Xian-Min Li, Meng-Yao Wu, Yan Zhang, Min Tao, Wei Li, Xiao-Ming Shen, Chong Zhou, Min Jiang BMC Cancer.2019;[Epub] CrossRef
STUDY OF VEGF-A AND TGF-Β LEVELS IN BIOPTATES OF SQUAMOUS CELL CARCINOMA OF THE TONGUE AND MOUTH FLOOR MUCOSA IN POLYCHEMOTHERAPY WITH MONOCLONAL ANTIBODIES – CETUXIMAB O. I. Kit, E. M. Frantsiyants, I. V. Neskubina, L. Yu. Vladimirova, A. A. Lyanova, Yu. A. Pogorelova, E. V. Shalashnaya, M. A. Еngibaryan, Yu. S. Sidorenko Research and Practical Medicine Journal.2019; 6(3): 20. CrossRef
Tumor progression-dependent angiogenesis in gastric cancer and its potential application Hsi-Lung Hsieh, Ming-Ming Tsai World Journal of Gastrointestinal Oncology.2019; 11(9): 686. CrossRef
Application effect of apatinib in patients with failure of standard treatment for advanced malignant tumours Guohui Liu, Chunbo Wang, Yunlong He, Mingyan E BMC Pharmacology and Toxicology.2019;[Epub] CrossRef
N-methyl-N-nitro-N-nitrosoguanidine-mediated ING4 downregulation contributed to the angiogenesis of transformed human gastric epithelial cells Yansu Chen, Rui Fu, Mengdie Xu, Yefei Huang, Guixiang Sun, Lichun Xu Life Sciences.2018; 199: 179. CrossRef
GSE1 predicts poor survival outcome in gastric cancer patients by SLC7A5 enhancement of tumor growth and metastasis Keshuo Ding, Sheng Tan, Xing Huang, Xiaonan Wang, Xiaocan Li, Rong Fan, Yong Zhu, Peter E. Lobie, Wenbin Wang, Zhengsheng Wu Journal of Biological Chemistry.2018; 293(11): 3949. CrossRef
Nanoparticles designed to regulate tumor microenvironment for cancer therapy Min Li, Fangrong Zhang, Yujie Su, Jianping Zhou, Wei Wang Life Sciences.2018; 201: 37. CrossRef
Gastric cancer vaccines synthesized using a TLR7 agonist and their synergistic antitumor effects with 5-fluorouracil Xiaodong Wang, Yu Liu, Yuwen Diao, Ningning Gao, Yanyan Wan, Jingjing Zhong, Huali Zheng, Zhulin Wang, Guangyi Jin Journal of Translational Medicine.2018;[Epub] CrossRef
ASO Author Reflections: Efficacy of Adjuvant S-1 Versus XELOX Chemotherapy for Gastric Cancer In-Hwan Kim Annals of Surgical Oncology.2018; 25(S3): 749. CrossRef
Identification of Bone Metastasis-associated Genes of Gastric Cancer by Genome-wide Transcriptional Profiling Mingzhe Lin, Xin Li, Haizhou Guo, Faxiang Ji, Linhan Ye, Xuemei Ma, Wen Cheng Current Bioinformatics.2018; 14(1): 62. CrossRef
Antiangiogenic effects of oridonin Lili Tian, Kangjie Xie, Donglai Sheng, Xiaoqing Wan, Guofu Zhu BMC Complementary and Alternative Medicine.2017;[Epub] CrossRef
The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer Dimakatso Alice Senthebane, Arielle Rowe, Nicholas Ekow Thomford, Hendrina Shipanga, Daniella Munro, Mohammad A. M. Al Mazeedi, Hashim A. M. Almazyadi, Karlien Kallmeyer, Collet Dandara, Michael S. Pepper, M. Iqbal Parker, Kevin Dzobo International Journal of Molecular Sciences.2017; 18(7): 1586. CrossRef
Efficacy and safety for Apatinib treatment in advanced gastric cancer: a real world study Yong Zhang, Chun Han, Juan Li, Li Zhang, Lijie Wang, Sisi Ye, Yi Hu, Li Bai Scientific Reports.2017;[Epub] CrossRef
Angiogenesis and Anti-Angiogenic Therapy in Gastric Cancer Henrik Nienhüser, Thomas Schmidt International Journal of Molecular Sciences.2017; 19(1): 43. CrossRef
Purpose
REVEL demonstrated improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) with docetaxel+ramucirumab versus docetaxel+placebo in 1,253 intent-to-treat (ITT) stage IV non-small cell lung cancer patients with disease progression following platinum-based chemotherapy. Results from the East Asian subgroup analysis are reported.
Materials and Methods
Subgroup analyses were performed in the East Asian ITT population (n=89). Kaplan-Meier analysis and Cox proportional hazards regression were performed for OS and PFS, and the Cochran-Mantel-Haenszel test was performed for response rate.
Results
In docetaxel+ramucirumab (n=43) versus docetaxel+placebo (n=46), median OS was 15.44 months versus 10.17 months (hazard ratio [HR], 0.762; 95% confidence interval [CI], 0.444 to 1.307), median PFS was 4.88 months versus 2.79 months (HR, 0.658; 95% CI, 0.408 to 1.060), and ORR was 25.6% (95% CI, 13.5 to 41.2) versus 8.7% (95% CI, 2.4 to 20.8). Due to increased incidence of neutropenia and febrile neutropenia in East Asian patients, starting dose of docetaxel was reduced for newly enrolled East Asian patients (75 to 60 mg/m2, n=24). In docetaxel+ramucirumab versus docetaxel+placebo, incidence of neutropenia was 84.4% versus 72.7% (75 mg/m2) and 54.5% versus 38.5% (60 mg/m2). Incidence of febrile neutropenia was 43.8% versus 12.1% (75 mg/m2) and 0% versus 7.7% (60 mg/m2).
Conclusion
Results of this subgroup analysis showed a trend favoring ramucirumab+docetaxel for median OS, PFS, and improved ORR in East Asian patients, consistent with ITT population results. Reduction of starting dose of docetaxel in East Asian patients was associated with improved safety.
Citations
Citations to this article as recorded by
Efficacy and outcomes of ramucirumab and docetaxel in patients with metastatic non-small cell lung cancer after disease progression on immune checkpoint inhibitor therapy: Results of a monocentric, retrospective analysis Samuel A. Kareff, Kunal Gawri, Khadeja Khan, Deukwoo Kwon, Estelamari Rodriguez, Gilberto de Lima Lopes, Richa Dawar Frontiers in Oncology.2023;[Epub] CrossRef
Clinical Trial and Real-World Outcomes of Patients With Metastatic NSCLC in the Post-Platinum–Based Chemotherapy Failure Setting Yu Yang Soon, Wesley Furnback, Jin Kim, Po-Ya Chuang, Gordon Chavez, Christina Proescholdt, Cloe Ying Chee Koh JTO Clinical and Research Reports.2023; 4(11): 100579. CrossRef
Safety and effectiveness of ramucirumab and docetaxel: a single-arm, prospective, multicenter, non-interventional, observational, post-marketing safety study of NSCLC in Japan Yucherng Chen, Soshi Nagaoka, Taeko Katayose, Nobuyuki Sekine Expert Opinion on Drug Safety.2022; 21(5): 691. CrossRef
Validity of the Cancer and Aging Research Group Predictive Tool in Older Japanese Patients Hirotaka Suto, Yumiko Inui, Atsuo Okamura Cancers.2022; 14(9): 2075. CrossRef
Cost-effectiveness analysis of pegfilgrastim in patients with non-small cell lung cancer receiving ramucirumab plus docetaxel in Japan Yu Kondo, Tomoya Tachi, Takayoshi Sakakibara, Jun Kato, Aki Kato, Takahito Mizuno, Yoshio Miyake, Hitomi Teramachi Supportive Care in Cancer.2022; 30(8): 6775. CrossRef
Sintilimab versus docetaxel as second‐line treatment in advanced or metastatic squamous non‐small‐cell lung cancer: an open‐label, randomized controlled phase 3 trial (ORIENT‐3) Yuankai Shi, Lin Wu, Xinmin Yu, Puyuan Xing, Yan Wang, Jianying Zhou, Airong Wang, Jianhua Shi, Yi Hu, Ziping Wang, Guangyu An, Yong Fang, Sanyuan Sun, Caicun Zhou, Changli Wang, Feng Ye, Xingya Li, Junye Wang, Mengzhao Wang, Yunpeng Liu, Yanqiu Zhao, Yin Cancer Communications.2022; 42(12): 1314. CrossRef
The Relevance of Docetaxel-related Febrile Neutropenia to Patient-reported Symptoms and the Quality of Life in Japanese, East Asian (Korean, Taiwanese), and Non-East Asian Patients Based on Post-hoc Analyses of Two Randomized Clinical Trials of Docetaxel Yukie Omori, Sotaro Enatsu, Alan J.M. Brnabic, Narayan Rajan, Jin-Yuan Shih, Joo-Hang Kim, Keunchil Park, Akira Inoue Haigan.2019; 59(7): 1140. CrossRef
Current and Emergent Therapy Options for Advanced Squamous Cell Lung Cancer Mark A. Socinski, Coleman Obasaju, David Gandara, Fred R. Hirsch, Philip Bonomi, Paul A. Bunn, Edward S. Kim, Corey J. Langer, Ronald B. Natale, Silvia Novello, Luis Paz-Ares, Maurice Pérol, Martin Reck, Suresh S. Ramalingam, Craig H. Reynolds, David R. S Journal of Thoracic Oncology.2018; 13(2): 165. CrossRef
Therapeutic perspectives for brain metastases in non-oncogene addicted non-small cell lung cancer (NSCLC): Towards a less dismal future? Stefano Frega, Laura Bonanno, Valentina Guarneri, Pierfranco Conte, Giulia Pasello Critical Reviews in Oncology/Hematology.2018; 128: 19. CrossRef
Ramucirumab Safety in East Asian Patients: A Meta-Analysis of Six Global, Randomized, Double-Blind, Placebo-Controlled, Phase III Clinical Trials Chia-Jui Yen, Kei Muro, Tae-Won Kim, Masatoshi Kudo, Jin-Yuan Shih, Keun-Wook Lee, Yee Chao, Sang-We Kim, Kentaro Yamazaki, JooHyuk Sohn, Rebecca Cheng, Yawei Zhang, Polina Binder, Gu Mi, Mauro Orlando, Hyun Cheol Chung Journal of Global Oncology.2018; (4): 1. CrossRef
Crizotinib versus Chemotherapy in Asian Patients with ALK-Positive Advanced Non-small Cell Lung Cancer Makoto Nishio, Dong-Wan Kim, Yi-Long Wu, Kazuhiko Nakagawa, Benjamin J. Solomon, Alice T. Shaw, Satoshi Hashigaki, Emiko Ohki, Tiziana Usari, Jolanda Paolini, Anna Polli, Keith D. Wilner, Tony Mok Cancer Research and Treatment.2018; 50(3): 691. CrossRef
The incidence and risk factors of febrile neutropenia in chemotherapy-naïve lung cancer patients receiving etoposide plus platinum Takumi Fujiwara, Hirotsugu Kenmotsu, Tateaki Naito, Takahisa Kawamura, Nobuaki Mamesaya, Mie Kotake, Haruki Kobayashi, Shota Omori, Kazuhisa Nakashima, Kazushige Wakuda, Akira Ono, Tetsuhiko Taira, Haruyasu Murakami, Katsuhiro Omae, Keita Mori, Masahiro E Cancer Chemotherapy and Pharmacology.2017; 79(6): 1229. CrossRef
The safety and efficacy of ramucirumab in combination with docetaxel in the treatment of lung cancer Valérie Paulus, Virginie Avrillon, Maurice Pérol Expert Review of Anticancer Therapy.2016; 16(11): 1119. CrossRef
Recommendations of the Austrian Working Group on Pulmonary Pathology and Oncology for predictive molecular and immunohistochemical testing in non-small cell lung cancer Helmut H. Popper, Ulrike Gruber-Mösenbacher, Georg Hutarew, Maximilian Hochmair, Gudrun Absenger, Luka Brcic, Leonhard Müllauer, Gerhard Dekan, Ulrike Setinek, Dagmar Krenbek, Michael Vesely, Robert Pirker, Wolfgang Hilbe, Rainer Kolb, Gerald Webersinke, memo - Magazine of European Medical Oncology.2016; 9(4): 191. CrossRef
Purpose
We recently reported on a randomized, open-label, phase 3 trial comparing pemetrexed-cisplatin chemotherapy followed by gefitinib maintenance therapy (PC/G) with gefitinib monotherapy in patients with non-small cell lung cancer (NSCLC). Here, we report on a post hoc subgroup analysis of that study assessing the demographics and disposition of the Korean patient subgroup, and comparing the tolerability of PC/G and gefitinib monotherapy and the tumor response with respect to epidermal growth factor receptor (EGFR) status.
Materials and Methods
Patients, who were ≥ 18 years, chemonaïve, Korean, light ex-smokers/never-smokers with advanced NSCLC, were randomly assigned (1:1) to PC/G or gefitinib monotherapy. Treatment-emergent adverse events (TEAEs) were graded, and tumor response was measured as change in lesion sum from baseline at best response. The study was registered with ClinicalTrials. gov, NCT01017874.
Results
Overall, 111 Korean patients were treated (PC/G, 51; gefitinib, 60). Between-arm characteristics were balanced and similar to those of the overall population. Treatment discontinuations due to adverse events were low (PC/G: 1, 2.0%; gefitinib: 7, 11.7%). Overall, 92 patients (82.9%) reported ≥ 1 TEAE (PC/G, 44; gefitinib, 48); few patients (PC/G, 16; gefitinib, 7) reported severe TEAEs; the most frequent was neutropenia (PC/G arm) and elevated alanine aminotransferase (gefitinib arm). The lesion sum was decreased by PC/G treatment in most patients, regardless of EGFRmutation status, while gefitinib monotherapy reduced the lesion sum in EGFR-positive patients but had no effect in EGFR-negative patients.
Conclusion
Our results confirm that both PC/G and gefitinib were well tolerated in Korean patients,
regardless of EGFR status; however, patients with EGFR wild-type NSCLC may not benefit
from gefitinib monotherapy.
Citations
Citations to this article as recorded by
Gefitinib for advanced non-small cell lung cancer Esther HA Sim, Ian A Yang, Richard Wood-Baker, Rayleen V Bowman, Kwun M Fong Cochrane Database of Systematic Reviews.2018;[Epub] CrossRef
Evidence suggests that combined gemcitabine-cisplatin chemotherapy extends survival in patients with advanced biliary tract cancer (BTC). We conducted a systematic review in order to collate this evidence and assess whether gemcitabine-cisplatin efficacy is influenced by primary tumor site, disease stage, or geographic region, and whether associated toxicities are related to regimen. MEDLINE (1946-search date), EMBASE (1966-search date), ClinicalTrials. gov (2008-search date), and abstracts from major oncology conferences (2009- search date) were searched (5 Dec 2013) using terms for BTC, gemcitabine, and cisplatin. All study types reporting efficacy (survival, response rates) or safety (toxicities) outcomes of gemcitabine-cisplatin in BTC were eligible for inclusion; efficacy data were extracted from prospective studies only. Evidence retrieved from one meta-analysis (abstract), four randomized controlled trials, 12 nonrandomized prospective studies, and three retrospective studies supported the efficacy and safety of gemcitabine-cisplatin for BTC. Median overall survival ranged from 4.6 to 11.7 months, and response rate ranged from 17.1% to 36.6%. Toxicities were generally acceptable and manageable. Heterogeneity in study designs and data collected prevented formal meta-analysis, however exploratory assessments suggested that efficacy did not vary with primary tumor site (gallbladder vs. others), disease stage (metastatic vs. locally advanced), or geographic origin (Asia vs. other). Incidence of grade 3/4 toxicities was not related to gemcitabine dose or cisplatin frequency. Despite individual variation in study designs, the evidence presented suggests that gemcitabine-cisplatin is effective in patients from a diverse range of countries and with heterogeneous disease characteristics. No substantial differences in toxicity were observed among the different dosing schedules of gemcitabine and cisplatin.
Citations
Citations to this article as recorded by
S3-Leitlinie „Diagnostik und Therapie des Hepatozellulären Karzinoms“ – Kurzversion Sabrina Groß, Michael Bitzer, Jörg Albert, Susanne Blödt, Judit Boda-Heggemann, Thomas Brunner, Reiner Caspari, Enrico De Toni, Frank Dombrowski, Matthias Evert, Markus Follmann, Paul Freudenberger, Cihan Gani, Andreas Geier, Eleni Gkika, Martin Götz, Tho Zeitschrift für Gastroenterologie.2024; 62(01): 73. CrossRef
S3-Leitlinie „Diagnostik und Therapie des Hepatozellulären Karzinoms“ – Langversion 4.0 Michael Bitzer, Sabrina Groß, Jörg Albert, Susanne Blödt, Judit Boda-Heggemann, Thomas Brunner, Reiner Caspari, Enrico De Toni, Frank Dombrowski, Matthias Evert, Markus Follmann, Paul Freudenberger, Cihan Gani, Andreas Geier, Eleni Gkika, Martin Götz, Tho Zeitschrift für Gastroenterologie.2024; 62(01): e67. CrossRef
Survival outcome of patient with pT1N0 biliary tract cancer treated with surgery alone Masaaki Kagoura, Shin Kobayashi, Motohiro Kojima, Masashi Kudo, Motokazu Sugimoto, Masaru Konishi, Naoto Gotohda European Journal of Surgical Oncology.2024; 50(3): 107980. CrossRef
S3-Leitlinie „Diagnostik und Therapie biliärer Karzinome“ – Langversion 4.0 Sabrina Groß, Michael Bitzer, Jörg Albert, Susanne Blödt, Judit Boda-Heggemann, Thomas Brunner, Reiner Caspari, Enrico De Toni, Frank Dombrowski, Matthias Evert, Markus Follmann, Paul Freudenberger, Cihan Gani, Andreas Geier, Eleni Gkika, Martin Götz, Tho Zeitschrift für Gastroenterologie.2024; 62(02): e213. CrossRef
S3-Leitlinie „Diagnostik und Therapie biliärer Karzinome“ – Kurzversion Michael Bitzer, Sabrina Groß, Jörg Albert, Susanne Blödt, Judit Boda-Heggemann, Thomas Brunner, Reiner Caspari, Enrico De Toni, Frank Dombrowski, Matthias Evert, Markus Follmann, Paul Freudenberger, Cihan Gani, Andreas Geier, Eleni Gkika, Martin Götz, Tho Zeitschrift für Gastroenterologie.2024; 62(02): 231. CrossRef
Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial Howard A Burris, Takuji Okusaka, Arndt Vogel, Myung Ah Lee, Hidenori Takahashi, Valeriy Breder, Jean-Frédéric Blanc, Junhe Li, Melinda Bachini, Magdalena Żotkiewicz, Jayne Abraham, Nikunj Patel, Julie Wang, Muzammil Ali, Nana Rokutanda, Gordon Cohen, Do-Y The Lancet Oncology.2024; 25(5): 626. CrossRef
Telotristat ethyl, a tryptophan hydroxylase inhibitor, enhances antitumor efficacy of standard chemotherapy in preclinical cholangiocarcinoma models Niranjan Awasthi, Lily Darman, Margaret A. Schwarz, Roderich E. Schwarz Journal of Cellular and Molecular Medicine.2024;[Epub] CrossRef
Clinical and biomarker analyses of sintilimab plus gemcitabine and cisplatin as first-line treatment for patients with advanced biliary tract cancer Tian-mei Zeng, Guang Yang, Cheng Lou, Wei Wei, Chen-jie Tao, Xi-yun Chen, Qin Han, Zhuo Cheng, Pei-pei Shang, Yu-long Dong, He-ming Xu, Lie-ping Guo, Dong-sheng Chen, Yun-jie Song, Chuang Qi, Wang-long Deng, Zhen-gang Yuan Nature Communications.2023;[Epub] CrossRef
S3-Leitlinie Diagnostik und Therapie biliärer Karzinome – Langversion Michael Bitzer, Sabrina Groß, Jörg Albert, Judit Boda-Heggemann, Thomas Brunner, Reiner Caspari, Enrico De Toni, Frank Dombrowski, Matthias Evert, Andreas Geier, Eleni Gkika, Martin Götz, Thomas Helmberger, Ralf-Thorsten Hoffmann, Peter Huppert, Achim Kau Zeitschrift für Gastroenterologie.2023; 61(04): e92. CrossRef
S3-Leitlinie Diagnostik und Therapie biliärer Karzinome Michael Bitzer, Sabrina Groß, Jörg Albert, Judit Boda-Heggemann, Thomas Brunner, Reiner Caspari, Enrico De Toni, Frank Dombrowski, Matthias Evert, Andreas Geier, Eleni Gkika, Martin Götz, Thomas Helmberger, Ralf-Thorsten Hoffmann, Peter Huppert, Achim Kau Zeitschrift für Gastroenterologie.2023; 61(04): 420. CrossRef
Pembrolizumab plus chemotherapy as first-line treatment for advanced biliary tract cancer Susanna Slater, David Cunningham The Lancet.2023; 401(10391): 1826. CrossRef
Anti-Cancer Activity of Verteporfin in Cholangiocarcinoma Jihye L. Golino, Xin Wang, Jing Bian, Benjamin Ruf, Michael Kelly, Baktiar O. Karim, Maggie C. Cam, Changqing Xie Cancers.2023; 15(9): 2454. CrossRef
Very rare metastatic phenomena of biliary tract cancer to the cerebellum: A case report and review of the literature Oadi N. Shrateh, Shadi Abu Saa International Journal of Surgery Case Reports.2023; 111: 108819. CrossRef
Comparison of Efficacy and Safety of Anti-Programmed Cell Death-1 Antibody Plus Lenvatinib and Chemotherapy as First-Line Therapy for Patients with Stage IV Gallbladder Cancer: A Real-World Study in a Chinese Population Tiantian Wu, Changsheng Pu, Qiang Wang, Keming Zhang Biomedicines.2023; 11(11): 2933. CrossRef
Effectivity of Palliative Care Bundle on Advanced Gallbladder Cancer: A Randomised Controlled Trial Kusum K. Rohilla, C. Vasantha Kalyani, Amit Gupta, Manoj Gupta, Nirmal Matella Indian Journal of Palliative Care.2023; 29: 447. CrossRef
Response of cholangiocarcinoma with epigastric metastasis to lenvatinib plus sintilimab: A case report and review of literature Wen-Hui Luo, Shao-Jun Li, Xue-Feng Wang World Journal of Gastrointestinal Oncology.2023; 15(11): 2033. CrossRef
S3-Leitlinie – Diagnostik und Therapie biliärer Karzinome M. Bitzer, S. Voesch, J. Albert, P. Bartenstein, W. Bechstein, S. Blödt, T. Brunner, F. Dombrowski, M. Evert, M. Follmann, C. La Fougère, P. Freudenberger, A. Geier, E. Gkika, M. Götz, E. Hammes, T. Helmberger, R. T. Hoffmann, W. P. Hofmann, P. Huppert, A Zeitschrift für Gastroenterologie.2022; 60(02): e186. CrossRef
S3-Leitlinie: Diagnostik und Therapie biliärer Karzinome M. Bitzer, S. Voesch, J. Albert, P. Bartenstein, W. Bechstein, S. Blödt, T. Brunner, F. Dombrowski, M. Evert, M. Follmann, C. La Fougère, P. Freudenberger, A. Geier, E. Gkika, M. Götz, E. Hammes, T. Helmberger, R. T. Hoffmann, W. P. Hofmann, P. Huppert, A Zeitschrift für Gastroenterologie.2022; 60(02): 219. CrossRef
Verteporfin synergizes the efficacy of anti-PD-1 in cholangiocarcinoma Jianyang Fu, Nicole A McGrath, Jihye Lee, Xin Wang, Gagandeep Brar, Changqing Xie Hepatobiliary & Pancreatic Diseases International.2022; 21(5): 485. CrossRef
Cytotoxic activities of ethanolic crude extracts from fruiting bodies of bamboo mushrooms (Dictyophora spp.) against cholangiocarcinoma cells Pathanin Chantree, Sirilak Chumkiew, Mantana Jamklang, Pongsakorn Martviset Research Results in Pharmacology.2022; 8(1): 33. CrossRef
LAG-3xPD-L1 bispecific antibody potentiates antitumor responses of T cells through dendritic cell activation Eunsil Sung, Minkyung Ko, Ju-young Won, Yunju Jo, Eunyoung Park, Hyunjoo Kim, Eunji Choi, Ui-jung Jung, Jaehyoung Jeon, Youngkwang Kim, Hyejin Ahn, Da-som Choi, Seunghyun Choi, Youngeun Hong, Hyeyoung Park, Hanbyul Lee, Yong-Gyu Son, Kyeongsu Park, Jonghw Molecular Therapy.2022; 30(8): 2800. CrossRef
Toripalimab in advanced biliary tract cancer Wei Li, Yueqi Wang, Yiyi Yu, Qian Li, Yan Wang, Chenlu Zhang, Xiaojing Xu, Xi Guo, Yu Dong, Yuehong Cui, Qing Hao, Lujia Huang, Houbao Liu, Tianshu Liu The Innovation.2022; 3(4): 100255. CrossRef
Selective Internal Radiation Therapy with Yttrium-90 for Intrahepatic Cholangiocarcinoma: A Systematic Review on Post-Treatment Dosimetry and Concomitant Chemotherapy Sedighe Hosseini Shabanan, Nariman Nezami, Mohamed E. Abdelsalam, Rahul Anil Sheth, Bruno C. Odisio, Armeen Mahvash, Peiman Habibollahi Current Oncology.2022; 29(6): 3825. CrossRef
Can patients with gallbladder adenocarcinoma and liver metastases obtain survival benefit from surgery? A population-based study Tianming Gao, Hua Tang, Baohuan Zhou, Dousheng Bai, Shengjie Jin, Chi Zhang, Guoqing Jiang Updates in Surgery.2022; 74(4): 1353. CrossRef
Pharmacophore Based Design of Probable FGFR-1 Inhibitors from the 3D
Crystal Structure of Infigratinib - A Drug Used in the Treatment of
Cholangiocarcinomas Koushik Sarker , Avijit Ghosh , Abhijit Saha, Suvasish Mishra, Subrata Sen Letters in Drug Design & Discovery.2022; 19(4): 314. CrossRef
Cannabidiol and Cannabigerol Inhibit Cholangiocarcinoma Growth In Vitro via Divergent Cell Death Pathways Michael J. Viereckl, Kelsey Krutsinger, Aaron Apawu, Jian Gu, Bryana Cardona, Donovan Barratt, Yuyan Han Biomolecules.2022; 12(6): 854. CrossRef
Idiopathic hyperammonemic encephalopathy secondary to gemcitabine–cisplatin treatment Karlijn Verkerk, Hans-Martin Otten, Alwin D. R. Huitema Cancer Chemotherapy and Pharmacology.2022; 90(5): 417. CrossRef
Enhanced gemcitabine cytotoxicity with knockdown of multidrug resistance protein genes in human cholangiocarcinoma cell lines Jiaqi Yang, David Sontag, Yuewen Gong, Gerald Y Minuk Journal of Gastroenterology and Hepatology.2021; 36(4): 1103. CrossRef
Biliary tract cancer Juan W Valle, R Katie Kelley, Bruno Nervi, Do-Youn Oh, Andrew X Zhu The Lancet.2021; 397(10272): 428. CrossRef
Current Status and Future Perspectives of Perioperative Therapy for Resectable Biliary Tract Cancer: A Multidisciplinary Review Changhoon Yoo, Sang Hyun Shin, Joon-Oh Park, Kyu-Pyo Kim, Jae Ho Jeong, Baek-Yeol Ryoo, Woohyung Lee, Ki-Byung Song, Dae-Wook Hwang, Jin-hong Park, Jae Hoon Lee Cancers.2021; 13(7): 1647. CrossRef
Thoracoscopic metastasectomy is the method of choice in the stepwise treatment of disseminated cholangiocellular carcinoma A.A. Pechetov, A.V. Chzhao, Sh.V. Ragimov, D.A. Volchansky, M.A. Makov, B.N. Gurmikov Onkologiya. Zhurnal imeni P.A.Gertsena.2021; 10(2): 39. CrossRef
IGF2BP1 IS A POOR PROGNOSTIC FACTOR IN EXTRAHEPATIC CHOLANGIOCARCINOMA Hung-Chune Maa, Yi-No Wu INTERNATIONAL JOURNAL OF SCIENTIFIC RESEARCH.2021; : 80. CrossRef
Efficacy and Safety of Gemcitabine Plus Cisplatin as Potential Preoperative Chemotherapy in Locally Advanced Intrahepatic, Perihilar, and Mid-Cholangiocarcinoma Lynn E. Nooijen, Lotte C. Franken, Ali Belkouz, Ikrame Oulad Abdennabi, Marc G. Besselink, Olivier R. Busch, Rutger-Jan Swijnenburg, Heinz-Josef Klümpen, Joris I. Erdmann American Journal of Clinical Oncology.2021; 44(10): 526. CrossRef
Novel biomarkers for cholangiocarcinoma: how can it enhance diagnosis, prognostication, and investigational drugs? Part-1 Ranu S Sinniah, Mark S Shapses, Mohammad Umar Ahmed, Hani Babiker, Sreenivasa R. Chandana Expert Opinion on Investigational Drugs.2021; 30(10): 1047. CrossRef
RRM1 Expression as a Prognostic Biomarker for Unresectable or Recurrent Biliary Tract Cancer Treated with Gemcitabine plus Cisplatin Jung Won Chun, Boyoung Lee, Weon Seo Park, Nayoung Han, Eun Kyung Hong, Eun Young Park, Sung Sik Han, Sang-Jae Park, Tae Hyun Kim, Woo Jin Lee, Sang Myung Woo Journal of Clinical Medicine.2021; 10(20): 4652. CrossRef
Effect of Photodynamic Therapy on Gemcitabine-Resistant Cholangiocarcinoma in vitro and in vivo Through KLF10 and EGFR Yang Yang, Jigang Li, Lei Yao, Lile Wu Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef
Lenvatinib Plus PD-1 Inhibitors as First-Line Treatment in Patients With Unresectable Biliary Tract Cancer: A Single-Arm, Open-Label, Phase II Study Qiyi Zhang, Xingyu Liu, Shumei Wei, Lufei Zhang, Yang Tian, Zhenzhen Gao, Ming Jin, Sheng Yan Frontiers in Oncology.2021;[Epub] CrossRef
Biliäre Karzinome: Zielstrukturen für eine molekulare Systemtherapie Sabrina Voesch, Michael Bitzer, Nisar Peter Malek Deutsches Ärzteblatt Online.2021;[Epub] CrossRef
Treatment of advanced gallbladder cancer: A SEER‐based study Weipu Mao, Fang Deng, Dongyan Wang, Li Gao, Xiuquan Shi Cancer Medicine.2020; 9(1): 141. CrossRef
LINC01714 Enhances Gemcitabine Sensitivity by Modulating FOXO3 Phosphorylation in Cholangiocarcinoma Sheng Shen, Jiwen Wang, Bohao Zheng, Ying Tao, Min Li, Yueqi Wang, Xiaoling Ni, Tao Suo, Houbao Liu, Han Liu, Jiwei Zhang Molecular Therapy - Nucleic Acids.2020; 19: 446. CrossRef
Multi-institutional retrospective analysis of FOLFIRI in patients with advanced biliary tract cancers Jonathan D Mizrahi, Valerie Gunchick, Kabir Mody, Lianchun Xiao, Phanikeerthi Surapaneni, Rachna T Shroff, Vaibhav Sahai World Journal of Gastrointestinal Oncology.2020; 12(1): 83. CrossRef
Low immune index correlates with favorable prognosis but with reduced benefit from chemotherapy in gallbladder cancer Jie Wang, Xiaobo Bo, Changcheng Wang, Yanlei Xin, Lingxi Nan, Rongkui Luo, Lingli Chen, Xiao Shi, Tao Suo, Xiaoling Ni, Han Liu, Sheng Shen, Min Li, Pinxiang Lu, Yueqi Wang, Houbao Liu Cancer Science.2020; 111(1): 219. CrossRef
Multi-institutional retrospective analysis of FOLFIRI in patients with advanced biliary tract cancers Jonathan D Mizrahi, Valerie Gunchick, Kabir Mody, Lianchun Xiao, Phanikeerthi Surapaneni, Rachna T Shroff, Vaibhav Sahai World Journal of Gastrointestinal Oncology.2020; 12(1): 83. CrossRef
Evaluation of NUC-1031: a first-in-class ProTide in biliary tract cancer Mansi Arora, James M. Bogenberger, Amro Abdelrahman, Jennifer L. Leiting, Xianfeng Chen, Jan B. Egan, Aradhana Kasimsetty, Elzbieta Lenkiewicz, Smriti Malasi, Pedro Luiz Serrano Uson, Bolni Marius Nagalo, Yumei Zhou, Marcela A. Salomao, Heidi E. Kosiorek, Cancer Chemotherapy and Pharmacology.2020; 85(6): 1063. CrossRef
NUC-1031 in biliary tract cancer: from bench to bedside and back? Lenka N. C. Boyd, Godefridus J. Peters, Geert Kazemier, Elisa Giovannetti Cancer Chemotherapy and Pharmacology.2020; 85(6): 1011. CrossRef
Targeting cancer stem cells in cholangiocarcinoma (Review) Nicole Mcgrath, Jianyang Fu, Sophie Gu, Changqing Xie International Journal of Oncology.2020; 57(2): 397. CrossRef
Phase 2 study of lenvatinib monotherapy as second-line treatment in unresectable biliary tract cancer: primary analysis results Makoto Ueno, Masafumi Ikeda, Takashi Sasaki, Fumio Nagashima, Nobumasa Mizuno, Satoshi Shimizu, Hiroki Ikezawa, Nozomi Hayata, Ryo Nakajima, Chigusa Morizane BMC Cancer.2020;[Epub] CrossRef
Combined treatment for locally advanced cholangiocellular liver cancer - the case report A. N. Polyakov, Yu. I. Patyutko, A. Yu. Syskova, K. A. Romanova, I. S. Bazin, O. N. Sergeeva, E. R. Virshke, E. S. Makarov, E. Yu. Antonova, A. A. Kirshin, D. V. Podluzhnyi Research and Practical Medicine Journal.2019; 6(4): 158. CrossRef
Translating the ABC-02 trial into daily practice: outcome of palliative treatment in patients with unresectable biliary tract cancer treated with gemcitabine and cisplatin J. Dierks, M. P. Gaspersz, A. Belkouz, J. L. A. van Vugt, R. J. S. Coelen, J. W. B. de Groot, A. J. ten Tije, W. G. Meijer, J. F. M. Pruijt, T. van Voorthuizen, D. J. van Spronsen, M. Rentinck, D. ten Oever, J. M. Smit, H. M. Otten, T. M. van Gulik, J. W. Acta Oncologica.2018; 57(6): 807. CrossRef
Tumor Marker Kinetics as Prognosticators in Patients with Unresectable Gallbladder Adenocarcinoma Undergoing Palliative Chemotherapy Jae Woo Lee, Yong-Tae Kim, Sang Hyub Lee, Jun Hyuk Son, Jin Woo Kang, Ji Kon Ryu, Dong Kee Jang, Woo Hyun Paik, Ban Seok Lee Gut and Liver.2018; 12(1): 102. CrossRef
Tumor-infiltrating mast cells predict prognosis and gemcitabine-based adjuvant chemotherapeutic benefit in biliary tract cancer patients Xiaobo Bo, Jie Wang, Tao Suo, Xiaoling Ni, Han Liu, Sheng Shen, Min Li, Yueqi Wang, Houbao Liu, Jiejie Xu BMC Cancer.2018;[Epub] CrossRef
Revision of bilateral self-expandable metallic stents placed using the stent-in-stent technique for malignant hilar biliary obstruction Jun Hyuk Son, Hee Seung Lee, Sang Hyub Lee, Seungmin Bang, Jinwoo Kang, Woo Hyun Paik, Ji Kon Ryu, Yong-Tae Kim Hepatobiliary & Pancreatic Diseases International.2018; 17(5): 437. CrossRef
Aktueller Therapiealgorithmus des intrahepatischen cholangiozellulären Karzinoms G. Lurje, J. Bednarsch, C. Roderburg, C. Trautwein, U. P. Neumann Der Chirurg.2018; 89(11): 858. CrossRef
Defining the Chance of Statistical Cure Among Patients with Extrahepatic Biliary Tract Cancer Gaya Spolverato, Fabio Bagante, Cecilia G. Ethun, George Poultsides, Thuy Tran, Kamran Idrees, Chelsea A. Isom, Ryan C. Fields, Bradley Krasnick, Emily Winslow, Clifford Cho, Robert C. G. Martin, Charles R. Scoggins, Perry Shen, Harveshp D. Mogal, Carl Sc World Journal of Surgery.2017; 41(1): 224. CrossRef
Comparison of FOLFIRINOX Chemotherapy with Other Regimens in Patients with Biliary Tract Cancers: a Retrospective Study Tulay Kus, Gokmen Aktas, Mehmet Emin Kalender, Alper Sevinc, Celaletdin Camci Journal of Gastrointestinal Cancer.2017; 48(2): 170. CrossRef
SVCT-2 determines the sensitivity to ascorbate-induced cell death in cholangiocarcinoma cell lines and patient derived xenografts Changzheng Wang, Hongwei Lv, Wen Yang, Ting Li, Tian Fang, Guishuai Lv, Qin Han, Liwei Dong, Tianyi Jiang, Beige Jiang, Guangshun Yang, Hongyang Wang Cancer Letters.2017; 398: 1. CrossRef
Prospective multicenter phase II study of gemcitabine plus cisplatin in patients with unresectable gallbladder cancer Yoshiki Hirooka, Takuya Ishikawa, Hiroki Kawashima, Eizaburo Ohno, Koji Nonogaki, Akira Kanamori, Takanori Hirai, Hiroki Uchida, Osamu Shirai, Hideki Ishikawa, Hidemi Goto Cancer Chemotherapy and Pharmacology.2017; 80(1): 119. CrossRef
CA19-9 or CEA Decline after the First Cycle of Treatment Predicts Survival in Advanced Biliary Tract Cancer Patients Treated with S-1 and Cisplatin Chemotherapy Dae-Won Lee, Seock-Ah Im, Yu Jung Kim, Yaewon Yang, Jiyoung Rhee, Im Il Na, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, In Sil Choi, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, Yung-Jue Bang Cancer Research and Treatment.2017; 49(3): 807. CrossRef
Prognostic factors in patients with advanced biliary tract cancer treated with first-line gemcitabine plus cisplatin: retrospective analysis of 740 patients Bum Jun Kim, Jaewon Hyung, Changhoon Yoo, Kyu-pyo Kim, Seong-Joon Park, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dong Wan Seo, Sung Koo Lee, Myung-Hwan Kim, Jin-hong Park, Hyungwoo Cho, Baek-Yeol Ryoo, Heung-Moon Chang Cancer Chemotherapy and Pharmacology.2017; 80(1): 209. CrossRef
Cholangiocarcinoma and its mimickers in primary sclerosing cholangitis Jonghun John Lee, Sebastian T Schindera, Hyun-Jung Jang, Scott Fung, Tae Kyoung Kim Abdominal Radiology.2017; 42(12): 2898. CrossRef
Impact of radiation dose in postoperative radiotherapy after R1 resection for extrahepatic bile duct cancer: long term results from a single institution Byoung Hyuck Kim, Eui Kyu Chie, Kyubo Kim, Jin-Young Jang, Sun Whe Kim, Do-Youn Oh, Yung-Jue Bang, Sung W. Ha Oncotarget.2017; 8(44): 78076. CrossRef
The efficacy and safety of different pharmacological interventions for patients with advanced biliary tract cancer: A network meta-analysis Xin-Fang Sun, Zhi-Kuan He, Jin-Ping Sun, Quan-Xing Ge, Er-Dong Shen Oncotarget.2017; 8(59): 100657. CrossRef
Gemcitabine and cisplatin in inoperable, loco-regionally advanced and metastatic gallbladder cancer: A study from Northern India cancer institute Vineet Talwar, Shubhra Raina, Varun Goel, Dinesh C. Doval International Journal of Hepatobiliary and Pancreatic Diseases.2017; 7(2): 1. CrossRef
Expression levels of ROS1/ALK/c-MET and therapeutic efficacy of cetuximab plus chemotherapy in advanced biliary tract cancer Nai-Jung Chiang, Chiun Hsu, Jen-Shi Chen, Hsiao-Hui Tsou, Ying-Ying Shen, Yee Chao, Ming-Huang Chen, Ta-Sen Yeh, Yan-Shen Shan, Shiu-Feng Huang, Li-Tzong Chen Scientific Reports.2016;[Epub] CrossRef
Chemotherapy for advanced biliary tract carcinoma Lawrence Chen, Chiehfeng Chen, Yun Yen, Ka-Wai Tam Medicine.2016; 95(33): e4584. CrossRef
The role of microRNAs in gallbladder cancer GANGHUA YANG, LEI ZHANG, RUIXIANG LI, LIN WANG Molecular and Clinical Oncology.2016; 5(1): 7. CrossRef
Advances in oncology research have led to identification of tumor-specific biomarkers, some of which are important predictive indicators and ideal targets for novel therapeutics. One such biomarker in non-small cell lung cancer (NSCLC) is the epidermal growth factor receptor (EGFR). Patients with NSCLC who harbor an activating EGFR mutation show a more favorable response to treatment with an EGFR inhibitor, such as gefitinib, erlotinib, or afatinib, than to chemotherapy. The prevalence of EGFR mutations in East Asian patients is higher than that in other populations, and in some clinical settings, patients have been treated with EGFR inhibitors based on clinicopathologic characteristics with no information on EGFR status. However, based on results from a series of studies in which East Asian patients with advanced non-squamous NSCLC were treated with EGFR inhibitors alone or in combination with standard chemotherapy, this may not be the best practice because EGFRmutation status was found to be a key predictor of outcome. Data from these studies highlight the necessity of EGFR testing in determining the most suitable treatment for patients with advanced or metastatic NSCLC.
Citations
Citations to this article as recorded by
Epidermal Growth Factor Receptor Mutation Status and the Impact on Clinical Outcomes in Patients with Non-Small Cell Lung Cancer HM Huang, Y Wei, JJ Wang, FY Ran, Y Wen, QH Chen, BF Zhang Balkan Journal of Medical Genetics.2023; 25(2): 29. CrossRef
EGFR Mutation Status in Lung Adenocarcinoma-Associated Malignant Pleural Effusion and Efficacy of EGFR Tyrosine Kinase Inhibitors Jiyoul Yang, Ok-Jun Lee, Seung-Myoung Son, Chang Gok Woo, Yusook Jeong, Yaewon Yang, Jihyun Kwon, Ki Hyeong Lee, Hye Sook Han Cancer Research and Treatment.2018; 50(3): 908. CrossRef
Traditional Korean Medicine for Skin Toxic Side Effects from Afatinib in a Non-Small Cell Lung Cancer Patient: A Case Report So-hyun Shim, Hee-jeong Seo, Jin-yong Choi, Go-eun Bae, Hyung-bum Seo, So-yeon Kim, Chang-woo Han, Seong-ha Park, Young-ju Yun, In Lee, Jung-nam Kwon, Jin-woo Hong, Jun-yong Choi The Journal of Internal Korean Medicine.2018; 39(5): 973. CrossRef
MET Exon 14 Skipping Mutations in Lung Adenocarcinoma: Clinicopathologic Implications and Prognostic Values Geun Dong Lee, Seung Eun Lee, Doo-Yi Oh, Dan-bi Yu, Hae Min Jeong, Jooseok Kim, Sungyoul Hong, Hun Soon Jung, Ensel Oh, Ji-Young Song, Mi-Sook Lee, Mingi Kim, Kyungsoo Jung, Jhingook Kim, Young Kee Shin, Yoon-La Choi, Hyeong Ryul Kim Journal of Thoracic Oncology.2017; 12(8): 1233. CrossRef
Predicting EGFR mutation status in lung cancer:Proposal for a scoring model using imaging and demographic characteristics Ali Sabri, Madiha Batool, Zhaolin Xu, Drew Bethune, Mohamed Abdolell, Daria Manos European Radiology.2016; 26(11): 4141. CrossRef
Clinicopathologic characteristics of EGFR, KRAS, and ALK alterations in 6,595 lung cancers Boram Lee, Taebum Lee, Se-Hoon Lee, Yoon-La Choi, Joungho Han Oncotarget.2016; 7(17): 23874. CrossRef
The Difference of Clinical Characteristics Between Patients With Exon 19 Deletion and Those With L858R Mutation in Nonsmall Cell Lung Cancer Yaxiong Zhang, Dacheng He, Wenfeng Fang, Shiyang Kang, Gang Chen, Shaodong Hong, Jin Sheng, Jianhua Zhan, Nan Chen, Zhihuang Hu, Cong Xue, Yunpeng Yang, Yuxiang Ma, Tao Qin, Ting Zhou, Yan Huang, Li Zhang Medicine.2015; 94(44): e1949. CrossRef
Purpose
This subgroup analysis of a phase II trial was conducted to assess possible ethnicity-based trends in efficacy and safety in East Asian (EA) and non-EA populations with nonsquamous non-small cell lung cancer (NSCLC).
Materials and Methods
Never-smoker patients (n=240) with locally advanced or metastatic nonsquamous NSCLC included 133 EA patients randomized to pemetrexed supplemented with dexamethasone, folic acid, and vitamin B12 plus erlotinib (pemetrexed-erlotinib) (n=41), erlotinib (n=49), or pemetrexed (n=43), and 107 non-EA patients randomized to pemetrexed-erlotinib (n=37), erlotinib (n=33), or pemetrexed (n=37). The primary endpoint, progression-free survival (PFS), was analyzed using a multivariate Cox model.
Results
Consistent with the results of the overall study, a statistically significant difference in PFS among the three arms was noted in the EA population favoring pemetrexed-erlotinib (overall p=0.003) as compared with either single-agent arm (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29 to 0.79; p=0.004 vs. erlotinib; HR, 0.40; 95% CI, 0.23 to 0.70; p=0.001 vs. pemetrexed). The EA patients treated with pemetrexed-erlotinib achieved a longer median PFS (7.4 months) compared with erlotinib (4.5 months) and pemetrexed (4.0 months). The PFS results also numerically favored pemetrexed-erlotinib in the non-EA population (overall p=0.210) (HR, 0.62; 95% CI, 0.37 to 1.05; p=0.078 vs. erlotinib; HR, 0.75; 95% CI, 0.42 to 1.32; p=0.320 vs. pemetrexed) (median PFS: pemetrexed-erlotinib, 6.7 months; erlotinib, 3.0 months; pemetrexed, 4.4 months).
Conclusion
The PFS results from this subset analysis in both EA and non-EA populations are consistent with the results in the overall population. The PFS advantage for pemetrexed-erlotinib is significant compared with the single agents in EA patients.
Citations
Citations to this article as recorded by
Association of Hypokalemia Incidence and Better Treatment Response in NSCLC Patients: A Meta-Analysis and Systematic Review on Anti-EGFR Targeted Therapy Clinical Trials Jiawei Zhou, Jianling Bai, Yuanping Yue, Xin Chen, Theis Lange, Dongfang You, Yang Zhao Frontiers in Oncology.2022;[Epub] CrossRef
Non-Smoking-Associated Lung Cancer: A distinct Entity in Terms of Tumor Biology, Patient Characteristics and Impact of Hereditary Cancer Predisposition Elisabeth Smolle, Martin Pichler Cancers.2019; 11(2): 204. CrossRef
Pemetrexed versus Gefitinib as Second-line Treatment for Advanced Non-small Cell Lung Cancer: A Meta-analysis Based on Randomized Controlled Trials Huiyu Wang, Zunjing Zhang, Feng Liu, Miaoying Zhou, Handi Lv Pteridines.2019; 30(1): 171. CrossRef
A Review of Regimens Combining Pemetrexed With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in the Treatment of Advanced Nonsquamous Non–Small-Cell Lung Cancer James Chih-Hsin Yang, Tony Mok, Baohui Han, Mauro Orlando, Tarun Puri, Keunchil Park Clinical Lung Cancer.2018; 19(1): 27. CrossRef
Randomized Phase 2 Trial of Pharmacodynamic Separation of Pemetrexed and Intercalated Erlotinib Versus Pemetrexed Alone for Advanced Nonsquamous, Non–small-cell Lung Cancer Tianhong Li, Bilal Piperdi, William V. Walsh, Mimi Kim, Laurel A. Beckett, Rasim Gucalp, Missak Haigentz, Venu G. Bathini, Huiyu Wen, Kaili Zhou, Patricia B. Pasquinelli, Srikanth Gajavelli, Meera Sreedhara, Xianhong Xie, Primo N. Lara, David R. Gandara, Clinical Lung Cancer.2017; 18(1): 60. CrossRef
Erlotinib intercalating pemetrexed/cisplatin versus erlotinib alone in Chinese patients with brain metastases from lung adenocarcinoma: a prospective, non-randomised, concurrent controlled trial (NCT01578668) Haihong Yang, Qiuhua Deng, Yuan Qiu, Jun Huang, Yubao Guan, Fengnan Wang, Xin Xu, Xinyun Yang ESMO Open.2017; 2: e000112. CrossRef
Gene mutation discovery research of non-smoking lung cancer patients due to indoor radon exposure Jung Ran Choi, Seong Yong Park, O Kyu Noh, Young Wha Koh, Dae Ryong Kang Annals of Occupational and Environmental Medicine.2016;[Epub] CrossRef
Epidermal Growth Factor Receptor Mutation Status in the Treatment of Non-small Cell Lung Cancer: Lessons Learned Dae Ho Lee, Vichien Srimuninnimit, Rebecca Cheng, Xin Wang, Mauro Orlando Cancer Research and Treatment.2015; 47(4): 549. CrossRef
Purpose A recent phase III study (PARAMOUNT) demonstrated that pemetrexed continuation maintenance therapy is a new treatment paradigm for advanced nonsquamous non-small cell lung cancer (NSCLC). The majority of patients enrolled in PARAMOUNT were Caucasian (94%). We reviewed efficacy and safety data from two clinical trials, which enrolled East Asian (EA) patients, to supplement data from PARAMOUNT on pemetrexed continuation maintenance therapy in patients with nonsquamous NSCLC. Materials and Methods Study S110 was a phase II, multicenter, randomized, controlled, open-label trial in never-smoker, chemonaïve, EA patients (n=31) with locally advanced or metastatic nonsquamous NSCLC (n=27). Study JMII was a multicenter, open-label, single-arm, postmarketing, clinical trial in Japanese patients (n=109) with advanced nonsquamous NSCLC. PARAMOUNT was a multicenter, randomized, double-blind, placebo-controlled trial in patients with advanced nonsquamous NSCLC. Results In EA patients with nonsquamous NSCLC, the median progression-free survival (PFS) for pemetrexed continuation maintenance therapy was 4.04 months (95% confidence interval [CI], 3.22 to 5.29 months) in study S110 and 3.9 months (95% CI, 3.2 to 5.2 months) in study JMII. The median PFS for pemetrexed continuation maintenance therapy in PARAMOUNT was 4.1 months (95% CI, 3.2 to 4.6 months). Pemetrexed continuation maintenance therapy in EA patients in studies S110 and JMII did not lead to any unexpected safety events, and was consistent with PARAMOUNT’s safety profile. Conclusion The efficacy and safety data in the EA trials were similar to those in PARAMOUNT despite differences in patient populations and study designs. These data represent consistent evidence for pemetrexed continuation maintenance therapy in EA patients with advanced nonsquamous NSCLC.
Citations
Citations to this article as recorded by
Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer (CameL): a randomised, open-label, multicentre, phase 3 trial Caicun Zhou, Gongyan Chen, Yunchao Huang, Jianying Zhou, LiZhu Lin, Jifeng Feng, Zhehai Wang, Yongqian Shu, Jianhua Shi, Yi Hu, QiMing Wang, Ying Cheng, Fengying Wu, Jianhua Chen, Xiaoyan Lin, Yongsheng Wang, Jianan Huang, Jiuwei Cui, Lejie Cao, Yunpeng L The Lancet Respiratory Medicine.2021; 9(3): 305. CrossRef
Survival Benefit and Genetic Profile of Pemetrexed as Initial Chemotherapy in Selected Chinese Patients With Advanced Lung Adenocarcinoma Long-Hua Guo, Ming-Feng Zhang, He-Long Zhang, Jian-Ying Zhou, Xiao-Hong Cai, Yu Long, Qi-Sen Guo, Nong Yang, Jun Zhao, Zhan-Hong Xie, Bo Jiang, Ying Zhu, Yun Fan, Cong-Ying Xie, Yi Hu, Yu Yao, Jun Jia, Xiao-Ling Li, Jiu-Wei Cui, Xi-Zhao Sui, Wen Lin, Ying Frontiers in Oncology.2020;[Epub] CrossRef
Effect of pemetrexed on brain metastases from nonsmall cell lung cancer with wild-type and unknown EGFR status Xiaoqing Yu, Yun Fan Medicine.2019; 98(3): e14110. CrossRef
Best Practices in Treatment Selection for Patients with Advanced NSCLC Mark A. Socinski, Nathan A. Pennell Cancer Control.2016; 23(4_suppl): 2. CrossRef