Journal ArticleDOI
Nivolumab treatment for oesophageal squamous-cell carcinoma: an open-label, multicentre, phase 2 trial
Toshihiro Kudo,Yasuo Hamamoto,Ken Kato,Takashi Ura,Takashi Kojima,Takahiro Tsushima,Shuichi Hironaka,Hiroki Hara,Taroh Satoh,Satoru Iwasa,Kei Muro,Hirofumi Yasui,Keiko Minashi,Kensei Yamaguchi,Atsushi Ohtsu,Yuichiro Doki,Yuko Kitagawa +16 more
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TLDR
Nivolumab showed promising activity with a manageable safety profile and could offer a potential new treatment approach for patients with treatment-refractory advanced squamous-cell carcinoma.Abstract:
Summary Background Nivolumab is a human monoclonal IgG4 antibody that inhibits programmed cell death protein 1 (PD-1) expressed on activated T cells. We investigated the safety and activity of nivolumab in patients with treatment-refractory oesophageal cancer. Methods We did an open-label, single-arm, multicentre phase 2 study. Eligible patients had advanced squamous-cell carcinoma, adenosquamous-cell carcinoma, or adenocarcinoma of the oesophagus refractory or intolerant to fluoropyrimidine-based, platinum-based, and taxane-based chemotherapy. Patients were treated with 3 mg/kg nivolumab given intravenously once every 2 weeks in 6-week cycles. The primary endpoint was centrally assessed objective response (the proportion of patients whose best response was complete or partial response), according to the Response Evaluation Criteria In Solid Tumors, version 1.1. Adverse events and treatment-related adverse events (defined as events for which a causal relation to nivolumab could not be ruled out) were monitored throughout the study. The safety analysis was done in patients who received at least one dose of nivolumab, and drug activity was assessed in patients who received at least one dose of nivolumab and had at least one central assessment of tumour response. This study is registered with clinicaltrials.jp, number ONO-4538-07/JapicCTI-No.142422. Follow-up of patients is ongoing. Findings Between Feb 25 and Nov 14, 2014, 65 patients were enrolled, all with squamous-cell carcinoma. 64 patients were assessable for the primary endpoint as one patient was excluded due to having multiple primary cancers; all patients were assessable for safety. Median follow-up was 10·8 months (IQR 4·9–14·3). 11 (17%, 95% CI 10–28) of 64 patients had a centrally assessed objective response. Of the 65 patients assessed for adverse events, the most common grade 3 or 4 events were grade 4 dyspnoea and hyponatraemia (one [2%) patient each), grade 3 lung infection (five [8%] patients), grade 3 decreased appetite (two [3%] patients), grade 3 increased blood creatinine phosphokinase (two [3%] patients), and grade 3 dehydration (two [3%] patients). Serious adverse events that occurred during the study were lung infection (four [6%] patients), dehydration (two [3%]), interstitial lung disease (two [3%]), and hyponatraemia, dyspnoea, fatigue, abnormal hepatic function, diarrhoea, bile duct stenosis, gastroenteritis, pneumonia, oedema, and back pain (one [2%] patient each). There were no treatment-related deaths. Interpretation Nivolumab showed promising activity with a manageable safety profile. This drug could offer a potential new treatment approach for patients with treatment-refractory advanced squamous-cell carcinoma. Funding Ono Pharmaceutical, Bristol-Myers Squibb.read more
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Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial
Ken Kato,Byoung Chul Cho,Masanobu Takahashi,Morihito Okada,Chen Yuan Lin,Keisho Chin,Shigenori Kadowaki,Myung-Ju Ahn,Yasuo Hamamoto,Yuichiro Doki,Chueh Chuan Yen,Yutaro Kubota,Sung Bae Kim,Chih-Hung Hsu,Eva Holtved,Ioannis Xynos,Mamoru Kodani,Yuko Kitagawa +17 more
TL;DR: Overall survival was significantly improved in the nivolumab group compared with the chemotherapy group, and a favourable safety profile compared with chemotherapy in previously treated advanced oesophageal squamous cell carcinoma patients.
Journal ArticleDOI
Treatment-Related Adverse Events of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-analysis.
Yucai Wang,Shouhao Zhou,Shouhao Zhou,Fang Yang,Xinyue Qi,Xin Wang,Xiaoxiang Guan,Xiaoxiang Guan,Chan Shen,Narjust Duma,Jesus Vera Aguilera,Ashish V. Chintakuntlawar,Katharine A. Price,Julian R. Molina,Lance C. Pagliaro,Thorvardur R. Halfdanarson,Axel Grothey,Axel Grothey,Svetomir N. Markovic,Grzegorz S. Nowakowski,Stephen M. Ansell,Michael L. Wang +21 more
TL;DR: Different PD-1 and PD-L1 inhibitors appear to have varying treatment-related adverse events; a comprehensive summary of the incidences of treatment- related adverse events in clinical trials provides an important guide for clinicians.
Journal ArticleDOI
Efficacy and Safety of Pembrolizumab for Heavily Pretreated Patients With Advanced, Metastatic Adenocarcinoma or Squamous Cell Carcinoma of the Esophagus: The Phase 2 KEYNOTE-180 Study.
Manish A. Shah,Takashi Kojima,Daniel Hochhauser,Peter C. Enzinger,Judith Raimbourg,Antoine Hollebecque,Florian Lordick,Sung Bae Kim,Masahiro Tajika,Heung Tae Kim,A. Craig Lockhart,Hendrik Tobias Arkenau,Farid El-Hajbi,Mukul Gupta,Per Pfeiffer,Qi Liu,Jared Lunceford,S. Peter Kang,Pooja Bhagia,Ken Kato +19 more
TL;DR: Where effective treatment options are an unmet need, pembrolizumab provided durable antitumor activity with manageable safety in patients with heavily pretreated esophageal cancer.
Journal ArticleDOI
Esophageal cancer practice guidelines 2017 edited by the Japan esophageal society: part 2
Yuko Kitagawa,Takashi Uno,Tsuneo Oyama,Ken Kato,Hiroyuki Kato,Hirofumi Kawakubo,Osamu Kawamura,Motoyasu Kusano,Hiroyuki Kuwano,Hiroya Takeuchi,Yasushi Toh,Yuichiro Doki,Yoshio Naomoto,Kenji Nemoto,Eisuke Booka,Hisahiro Matsubara,Tatsuya Miyazaki,Manabu Muto,Akio Yanagisawa,Masahiro Yoshida +19 more
TL;DR: Endoscopic resection includes endoscopic mucosal resection (EMR), wherein the affected mucosal lesion is held or aspirated and resected with a snare, and endoscopic submucosal dissection (ESD), which refers to en bloc resection of an extensive lesion using an IT knife or hook knife.
Journal ArticleDOI
Camrelizumab versus investigator's choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study.
Jing Huang,Jianming Xu,Chen Yun,Wu Zhuang,Yiping Zhang,Zhendong Chen,Jia Chen,Helong Zhang,Zuoxing Niu,Qingxia Fan,Lizhu Lin,Kangsheng Gu,Ying Liu,Yi Ba,Zhanhui Miao,Xiaodong Jiang,Ming Zeng,Jianhua Chen,Zhichao Fu,Lu Gan,Jun Wang,Xianbao Zhan,Tianshu Liu,Zhiping Li,Lin Shen,Yongqian Shu,Tao Zhang,Qing Yang,Jianjun Zou,Suxia Luo,Feng Peng,Gang Wu,Nong Xu,Lin Zhao,Dong Ma,Shukui Qin,Wei Ren,Enxiao Li,H. Lu,Yueyin Pan,Jianping Xiong,Ying Yuan,Yuxian Bai,Lei Chen,Yi Hu,Li Zhang,Yong Gao +46 more
TL;DR: Second-line camrelizumab significantly improved overall survival in patients with advanced or metastatic oesophageal squamous cell carcinoma compared with chemotherapy, with a manageable safety profile.
References
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Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer
Hossein Borghaei,Luis Paz-Ares,Leora Horn,D. R. Spigel,M. Steins,Neal Ready,L.Q. Chow,Everett E. Vokes,Enriqueta Felip,Esther Holgado,F. Barlesi,M. Kohlhufl,Oscar Arrieta,Marco Angelo Burgio,J. Fayette,H. Lena,Elena Poddubskaya,David E. Gerber,Scott N. Gettinger,Charles M. Rudin,Naiyer A. Rizvi,L. Crina,G. R. Blumenschein,Scott J. Antonia,C. Dorange,C. T. Harbison,F. Graf Finckenstein,Julie R. Brahmer +27 more
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Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer
Julie R. Brahmer,Karen L. Reckamp,Paul Baas,Lucio Crinò,Wilfried Eberhardt,Elena Poddubskaya,Scott J. Antonia,Adam Pluzanski,Everett E. Vokes,Esther Holgado,David M. Waterhouse,Neal Ready,Justin F. Gainor,Osvaldo Arén Frontera,Libor Havel,Martin Steins,Marina Chiara Garassino,Joachim G.J.V. Aerts,Manuel Domine,Luis Paz-Ares,Martin Reck,Christine Baudelet,Christopher T. Harbison,Brian Lestini,David R. Spigel +24 more
TL;DR: Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level.
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