525 Safety and efficacy of pembrolizumab (MK-3475) in patients (pts) with advanced biliary tract cancer: Interim results of KEYNOTE-028

Bang, Yung‐Jue; Doi, Takehiko; Braud, Filippo de; Piha-Paul, S. A.; Hollebecque, Antoine; Razak, Albiruni Ryan Abdul; Lin, Chou-Ching K.; Ott, Peter; He, Andy; Yuan, Sammy; Koshiji, Minori; Lam, Brian; Aggarwal, Rakesh

doi:10.1016/s0959-8049(16)30326-4

Cited by 139 publications

(117 citation statements)

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“…Documented response to anti-CTLA-4 therapy has been observed, manifesting as a delayed response after initial disease progression [59] . The early data for anti-PD1 inhibition has been recently presented, showing encouraging evidence of efficacy, and which seems consistent with use of this agent in other solid tumor studies [60] .…”

Section: Biliary Tract Carcinomassupporting

confidence: 72%

Treating Hepatobiliary Cancer: The Immunologic Approach

Duffy

Greten²

2017

Dig Dis

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Hepatobiliary cancer comprises a heterogeneous group of malignancies in which the standard treatments for advanced disease are minimally effective and evolve slowly over time. Like the majority of gastrointestinal cancers, with some notable exceptions, the impact of immune-based approaches is yet to be experienced. Notwithstanding this, the etiological background of hepatobiliary cancer - overlapping in almost every known causative or associated factor with inflammation - provides a strong clue that these approaches may have an impact on this group of diseases. This review seeks to put the management of hepatobiliary cancers in the context of its inflammation-based etiology, with the aim of pointing to the therapeutic opportunities in immune-based approaches currently entering the clinic or those that are about to do so.

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Section: Biliary Tract Carcinomassupporting

confidence: 72%

Treating Hepatobiliary Cancer: The Immunologic Approach

Duffy

Greten²

2017

Dig Dis

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“…The genetic heterogeneity between individual biliary tract cancers suggests that treatment should be individualized, or "custom-made", according to tumor mutation status in some cases. In support of this hypothesis, clinical trials of several novel targeted agents for genetically-defined subsets of biliary tract cancers show promising efficacy, including the IDH1 inhibitor, AG-120, for IDH-1-mutant cholangiocarcinoma (23), the pan-FGFR inhibitor BGJ398 for intrahepatic cholangiocarcinoma harboring FGFR2 gene fusions or other FGFR pathway aberrations (24), and the immune checkpoint inhibitor pembrolizumab for biliary tract cancers with defects in mismatch repair genes (25). These exciting data support ongoing efforts to better define anatomic, molecular, and genetic subsets of biliary tract cancers for stratification and enrichment in clinical trials of targeted therapies to identify patients most likely to respond, so that we may move towards custommade therapy for patients suffering from this complex and heterogeneous family of cancers.…”

Section: Adjuvant Therapy For Cholangiocarcinoma: Different Viewsmentioning

confidence: 97%

Advances in cholangiocarcinoma research: report from the third Cholangiocarcinoma Foundation Annual Conference

Abou‐Alfa

Andersen

Chapman

et al. 2016

J. Gastrointest. Oncol.

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“…For 24 patients with biliary tract cancer, the ORR was again unsatisfactory at 17.4%. 73 One patient had grade 3 immune hemolytic anemia requiring drug discontinuation, and 1 patient had grade 3 colitis. In another cohort of oesophageal cancer (adenocarcinoma, N D 17; squamous cell carcinoma, N D 5, mucoepidermoid carcinoma, N D 1), the ORR was 30%.…”

Section: Other Trials Of Pembrolizumab As a Single Agentmentioning

confidence: 99%

Pembrolizumab (Keytruda)

Kwok

Yau

Chiu

et al. 2016

Human Vaccines & Immunotherapeutics

301

224

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The programmed cell death protein 1 (PD1) is one of the checkpoints that regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2 results in transduction of negative signals to T-cells. PD1 expression is an important mechanism contributing to the exhausted effector T-cell phenotype. The expression of PD1 on effector T-cells and PDL1 on neoplastic cells enables tumor cells to evade anti-tumor immunity. Blockade of PD1 is an important immunotherapeutic strategy for cancers. Pembrolizumab (Keytruda) is a humanized monoclonal anti-PD1 antibody that has been extensively investigated in numerous malignancies. In melanoma refractory to targeted therapy, pembrolizumab induced overall response rates (ORRs) of 21-34%. It was superior to another immune checkpoint inhibitor ipilimumab (Yervoy) in stage III/IV unresectable melanoma. In refractory non-small cell lung cancer (NSCLC), pembrolizumab induced ORRs of 19-25%. Based on these results, pembrolizumab was approved by the USA FDA for the treatment of advanced melanoma and NSCLC. Tumor cell PDL1 expression may be a valid response predictor. Molecular analysis also showed that tumors with high gene mutation burdens, which might result in the formation of more tumor-related neo-antigens, had better responses to pembrolizumab. In malignancies including lymphomas and other solid tumors, preliminary data showed that ORRs of around 20-50 % could be achieved. Adverse events occurred in up to 60% of patients, but grade 3/4 toxicities were observed in <10% of cases. Immune-related adverse events including thyroid dysfunction, hepatitis and pneumonitis are more serious and may lead to cessation of treatment.

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525 Safety and efficacy of pembrolizumab (MK-3475) in patients (pts) with advanced biliary tract cancer: Interim results of KEYNOTE-028

Cited by 139 publications

References 0 publications

Treating Hepatobiliary Cancer: The Immunologic Approach

Treating Hepatobiliary Cancer: The Immunologic Approach

Advances in cholangiocarcinoma research: report from the third Cholangiocarcinoma Foundation Annual Conference

Pembrolizumab (Keytruda)

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