Gefitinib for oesophageal cancer progressing after chemotherapy (COG): a phase 3, multicentre, double-blind, placebo-controlled randomised trial

Dutton, Susan; Ferry, David; Blazeby, Jane M; Abbas, Haider; Dahle-Smith, Åsa; Mansoor, Wasat; Thompson, Joyce; Harrison, Mark; Chatterjee, Anirban; Falk, Stephen; Garcia-Alonso, Angel; Fyfe, D.; Hubner, Richard A; Gamble, T.; Peachey, L.; Davoudianfar, Mina; Pearson, Sarah; Julier, Patrick; Jankowski, Janusz; Kerr, David J.; Petty, Russell

doi:10.1016/s1470-2045(14)70024-5

Cited by 276 publications

(248 citation statements)

References 26 publications

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“…Immunotherapies are under investigation with several studies targeting tyrosine-kinase receptors and epidermal growth factor receptors with limited success [15]. In particular, the Cancer Oesophagus Gefitinib (COG) trial investigated the effectiveness of gefitinib for oesophageal cancer after chemotherapy with no improvement in overall survival [19].…”

Section: Managementmentioning

confidence: 99%

Oesophageal Squamous Dysplasia

Auld

Srinath

Jeyarajan

2018

J Gastrointest Canc

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Section: Managementmentioning

confidence: 99%

Oesophageal Squamous Dysplasia

Auld

Srinath

Jeyarajan

2018

J Gastrointest Canc

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“…V případě spinocelulárních nádorů jícnu se širšího uplatnění žádná cílená terapie zatím nedočkala. Původně slibné výsledky anti-EGFR léčby s gefitinibem nebyly potvrzeny ve studiích fáze III [3]. Imunoterapie se v posledních letech etablovala jako základní léčebná modalita v systémové léčbě řady malignit vč.…”

Section: úVodunclassified

Current Status of Checkpoint Inhibitors in the Treatment of Esophageal and Gastric Tumors – Overview of Studies

Vrána¹,

Matzenauer²,

Melichar³

2018

Klin Onkol

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SouhrnVýchodiska: Nádory žaludku a jícnu představují i přes současné pokroky v onkologické léčbě onemocnění se špatnou prognózou. Jedinou potencionálně kurativní léčbu představuje stále chirurgická resekce doplněná neoadjuvantní či adjuvantní chemoterapií/ chemoradioterapií. U generalizovaného onemocnění, na rozdíl od jiných nádorů, cílená terapie bohužel dosud nepřinesla větší posun s výjimkou trastuzumabu a ramucirumabu, jejichž účinnost je však relativně omezená. Imunoterapie přestavuje rychle se rozvíjející léčebnou modalitu, která se dostala do standardních léčebných postupů u řady malignit. V našem přehledovém článku shrnujeme dosavadní klinické studie s checkpoint inhibitory u nádorů žaludku a jícnu, dosud publikované výsledky a perspektivy probíhajících studií. Výsledky a diskuze: Karcinomy žaludku a jícnu patří mezi malignity s největší mutační náloží, což již od počátku přitahovalo zájem o imunoterapii u těchto typů nádorů. Prvotní studie fáze I (KEYNOTE 012, Javelin, KEYNOTE 028) upozornily na efektivitu a přijatelnou toxicitu checkpoint inhibitorů u nádorů žaludku a jícnu. Následo-valy studie fáze II (KEYNOTE 059, CheckMate 032, JapicCTI-No.142422), které ukázaly odpověď nádoru v 10-30 % případů a potvrdily prediktivní roli exprese PD-L1. Probíhající studie fáze III (CheckMate 648, KEYNOTE 181, KEYNOTE 590, CheckMate 577) by měly definitivně potvrdit efektivitu checkpoint inibitorů a jejich postavení v paliativních i adjuvantních režimech. Závěr: Checkpoint inhibitory představují perspektivní léčebnou modalitu u nádorů žaludku a jícnu. Klíčová slova nádory žaludku -nádory jícnu -imunoterapie SummaryBackground: Despite recent advances in oncological treatment, gastric and esophageal cancer remain neoplastic dis eases with poor prognoses. The only potential curative treatment is surgical resection with adjuvant or neoadjuvant chemother apy/ chemoradiother apy. Targeted ther apy of metastatic dis ease unfortunately does not provide better outcomes than for other tumor types, with the exception of trastuzumab and ramucirumab, which have relatively limited efficacy. Immunother apy is a rapidly evolv ing treatment that has influenced the treatment guidelines for many tumors. In the present review, we summarize clinical trials of checkpoint inhibitors for the treatment of gastric and esophageal cancer, includ ing published results and the perspectives of ongo ing trials. Results and Discussion: Gastric and esophageal cancer are tumors with high mutation loads that have attracted considerable attention since the beginn ing of interest in immunother apy. Phase I clinical trials (Keynote 012, Javelin, KEY-NOTE 028) have demonstrated efficacy and acceptable toxicity. These studies were followed by phase II clinical trials (KEYNOTE 059, CheckMate 032, JapicCTI-No.142422), which showed about a 10-30% over all tumor response rate and confirmed the predictive role of PD-L1 expression. Ongo ing phase III clinical trials (CheckMate 648, KEYNOTE 181, KEYNOTE 590, CheckMate 577) should finally confirm whether checkpoin...

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“…Many drugs targeting RTKs have been evaluated in ESCC. The small molecular inhibitors for EGFR, gefitinib (Iressa) and erlotinib (Tarceva) have been evaluated in esophageal cancer in phase II and phase III studies (15)(16)(17)(18). Disease control after second-line gefitinib treatment was observed in advanced ESCC patients in a phase II study (5 of 9 patients; 55 %) (16).…”

Section: Esophageal Cancermentioning

confidence: 99%

“…Disease control after second-line gefitinib treatment was observed in advanced ESCC patients in a phase II study (5 of 9 patients; 55 %) (16). However, in a large-sized phase III study, the use of gefitinib as a second-line treatment in esophageal cancer did not result in improvement of overall survival (15). Response to erlotinib was also observed in patients with ESCC in a phase II study (18).…”

Section: Esophageal Cancermentioning

confidence: 99%

Translational research in thoracic surgery—the National Taiwan University Hospital experience

2016

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Thoracic surgeons should be more aware of the latest information about histopathological, genetic and epigenetic alterations that may influence treatment policy and patient outcome in the biomolecular era. Translational research studies often produce a promising diagnostic tool or new treatment that can be used clinically. The results of these translational studies may even change the practical guidelines and current staging system in thoracic malignancies. The following article summarizes the experiences of translational research in esophageal cancer and non-small cell lung cancer (NSCLC) at National Taiwan University Hospital in Taiwan.

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Gefitinib for oesophageal cancer progressing after chemotherapy (COG): a phase 3, multicentre, double-blind, placebo-controlled randomised trial

Abstract: Cancer Research UK.

Cited by 276 publications

References 26 publications

Oesophageal Squamous Dysplasia

Oesophageal Squamous Dysplasia

Current Status of Checkpoint Inhibitors in the Treatment of Esophageal and Gastric Tumors – Overview of Studies

Translational research in thoracic surgery—the National Taiwan University Hospital experience

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