502 Pembrolizumab (MK-3475) for patients (pts) with advanced colorectal carcinoma (CRC): Preliminary results from KEYNOTE-028

O’Neil, Bert H.; Wallmark, John M.; Lorenté, David; Élez, Elena; Raimbourg, Judith; Gomez‐Roca, Carlos; Ejadi, Samuel; Piha-Paul, S. A.; Moss, Rebecca A.; SIu, Lopukhin; Dotti, Katia; Santoro, Armando; Gould, Milena; Yuan, Shukai; Koshiji, Minori; Han, SW

doi:10.1016/s0959-8049(16)30304-5

Cited by 19 publications

(16 citation statements)

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“…In 23 patients with advanced CRC, the ORR was merely 4.3%. 72 The only responder had microsatellite instability due to mutation of the MLH1 gene promoter. For 24 patients with biliary tract cancer, the ORR was again unsatisfactory at 17.4%.…”

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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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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“…were enrolled and treated with pembrolizumab with promising results: 4 patients (17%) had a partial response and 4 (17%) had stable disease. 92 Durable responses were obtained with pembrolizumab in patients with advanced biliary tract cancer expressing PD-L1. 89,93,94 KEYNOTE-158, a phase II basket trial of pembrolizumab in cancer patients including CCA with disease progression on standard therapy, is ongoing.…”

Section: Immunotherapy: Checkpoint Modulators (Ctla4 Pd1/pdl1 Cd4mentioning

confidence: 98%

Medical treatment for cholangiocarcinoma

Adeva

Sangro

Salati

et al. 2019

Liver International

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Most of the patients with cholangiocarcinoma (CCA) present with advanced (inoperable or metastatic) disease, and relapse rates are high in those undergoing potentially curative resection. Previous treatment nihilism of patients with advanced disease has been replaced by active clinical research with the advent of randomized clinical trials (RCTs) and a much greater effort at understanding molecular mechanisms underpinning CCA. Three RCTs have recently been reported evaluating adjuvant chemotherapy following curative resection; only one of these has the potential to change practice. The BILCAP study failed to meet its primary endpoint by intention‐to‐treat analysis; however, a survival benefit was seen in a preplanned sensitivity analysis (predominantly adjusting for lymph nodes status). This, along with the numerical difference in median overall survival has led to the uptake of adjuvant capecitabine by many clinicians. In patients with advanced disease, the only level 1 data available supports the use of cisplatin and gemcitabine for the first‐line treatment of patients with advanced disease; there is no established second‐line chemotherapy. Previous forays into targeted therapy have proven unfruitful (namely targeting the epithelial growth factor receptor and vascular endothelial growth factor pathways). An increasing number of genomic subtypes are being defined; for some of these on‐target therapeutic options are under active investigation. The most developed are studies targeting IDH‐1 (isocitrate dehydrogenase) mutations and FGFR‐2 (fibroblast growth factor receptor) fusions, with promising early results. Several other pathways are under evaluation, along with early studies targeting the immune environment; these are too premature to change practice to date. These emerging treatments are discussed.

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“…В области КРР новые данные свидетельствуют о том, что экспрессия PDL-1 может не иметь такого же прогностического значения. В исследовании Keynote-028 лишь один из 23 пациентов мКРР с экспрессией PD-L1 продемонстрировал ответ на пембролизумаб, и тот, как оказалось, имел опухоль с dMMR [52]. Отсутствие корреляции между экспрессией PD-L1 и эффективностью ниволумаба у пациентов в dMRR было отмечено и в исследовании Checkmate-142 [53].…”

Section: таблица1 клинические исследования с применением чекпоинт-инunclassified

Modern views on immunological biomarkers of colon cancer

et al. 2019

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The article briefly describes the mechanism of action of immunotherapeutic drugs that suppress the activity of “checkpoints” of the immune response CTLA-4 and PD-1. Modern methods of clinical efficacy and advantages of applying nivolumab, pembrolizumab and atezolizumab in colorectal cancer. The existing evidence base of the potential predictive and prognostic role of MSI status is summarized and presented information on the prospects for the further development of this therapeutical treatment of malignant tumors.

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502 Pembrolizumab (MK-3475) for patients (pts) with advanced colorectal carcinoma (CRC): Preliminary results from KEYNOTE-028

Cited by 19 publications

References 0 publications

Pembrolizumab (Keytruda)

Pembrolizumab (Keytruda)

Medical treatment for cholangiocarcinoma

Modern views on immunological biomarkers of colon cancer

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