A Phase 1B Study of Pembrolizumab (Pembro; Mk-3475) in Patients (Pts) with Advanced Gastric Cancer

Muro, Kei; Bang, Yung Jue; Shankaran, Veena; Geva, Ravit; Catenacci, Daniel V.T.; Gupta, Shilpa; Eder, Joseph P.; Berger, Raanan; Gonzalez, Edward J.; Pulini, Jennifer; Ray, Assaf; Dolled‐Filhart, Marisa; Emancipator, Kenneth; Pathiraja, Kumudu; Shu, Xinxin; Koshiji, Minori; Cheng, Jonathan D.; Chung, Hyun-Chul

doi:10.1093/annonc/mdu438.15

Cited by 55 publications

(35 citation statements)

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“…in GC using monoclonal antibodies has been explored in experimental models (54) , and evaluated in a phase Ib trial, which demonstrated antitumor activity of pembrolizumab in an enriched PD-L1-positive population composed of 39 GC patients (55) . Pembrolizumab is also currently being tested in a phase II study evaluating its efficacy in previously treated HER2-negative advanced GC (clinicaltrials.govNCT02335411).…”

Section: Pd-1/pd-l1 Pd-l2 Pathwaymentioning

confidence: 99%

Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

Jácome

Lima

Kazzi

et al. 2016

Rev. Soc. Bras. Med. Trop.

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Approximately 90% of the world population is infected by Epstein-Barr virus (EBV). Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancerrelated mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma.

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Section: Pd-1/pd-l1 Pd-l2 Pathwaymentioning

confidence: 99%

Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

Jácome

Lima

Kazzi

et al. 2016

Rev. Soc. Bras. Med. Trop.

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“…One approach to overcome that immune response inhibition has been to target immune checkpoints w ith blocking monoclonal antibodies. Early-phase studies in gc using antibodies such pembrolizumab and nivolumab showed encouraging results, but further studies are needed to confirm activity 108,109 .…”

Section: Summary Of Evidencementioning

confidence: 99%

Report from the 17th Annual Western Canadian Gastrointestinal Cancer Consensus Conference; Edmonton, Alberta; 11–12 September 2015

et al. 2016

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The 17th annual Western Canadian Gastrointestinal Cancer Consensus Conference (wcgccc) was held in Edmonton, Alberta, 11-12 September 2015. The wcgccc is an interactive multidisciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of gastric cancer.

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“…Recently, pembrolizumab showed promising activity in gastric [45], urothelial [46], head and neck [47], and nonsmall cell lung (NSCLC) [48] cancers and is now being investigated in several trials alone or in combination with other drugs (Tables 2 and 3). …”

Section: Clinical Experience With Anti-pd-1 Antibodiesmentioning

confidence: 99%

Reorienting the immune system in the treatment of cancer by using anti-PD-1 and anti-PD-L1 antibodies

Borch

Donia

Andersen

et al. 2015

Drug Discovery Today

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A Phase 1B Study of Pembrolizumab (Pembro; Mk-3475) in Patients (Pts) with Advanced Gastric Cancer

Cited by 55 publications

References 0 publications

Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

Report from the 17th Annual Western Canadian Gastrointestinal Cancer Consensus Conference; Edmonton, Alberta; 11–12 September 2015

Reorienting the immune system in the treatment of cancer by using anti-PD-1 and anti-PD-L1 antibodies

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