KEYNOTE-164: Phase 2 study of pembrolizumab for patients with previously treated, microsatellite instability-high advanced colorectal carcinoma.

Le, Dung T.; Thewis, André; Kim, Tae Won; Cutsem, Éric Van; Jäger, Dirk; Geva, Ravit; Hara, Hiroki; Kim, Tae-You; Yoshino, Takayuki; Burge, Matthew; Taniguchi, H.; Élez, Elena; Atreya, Chloé E.; Bendell, Johanna C.; Koshiji, Minori; Kang, Soonmo Peter; Díaz, Luis A.

doi:10.1200/jco.2016.34.15_suppl.tps3631

Cited by 5 publications

(4 citation statements)

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“…On the other hand, in the cohort of pMMR CRCs no immune-related and RECIST ORR were observed and the immune-related PFS rate at 20 weeks was 11% [25]. Based on these considerations, a phase II (KEYNOTE-164) and a phase III (KEYNOTE-177) clinical trials evaluating pembrolizumab in dMMR CRCs are ongoing [7, 8]. Overman et al published a phase 2 trial on 74 patients with dMMR/MSI-H heavily pretreated recurrent or metastatic CRCs treated with nivolumab.…”

Section: Patients Selection For Immunotherapy: the Role Of Geneticmentioning

confidence: 99%

Patients Selection for Immunotherapy in Solid Tumors: Overcome the Naïve Vision of a Single Biomarker

Signorelli

Giannatempo

Grazia

et al. 2019

BioMed Research International

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Immunotherapy, and in particular immune-checkpoints blockade therapy (ICB), represents a new pillar in cancer therapy. Antibodies targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) and Programmed Death 1 (PD-1)/Programmed Death Ligand-1 (PD-L1) demonstrated a relevant clinical value in a large number of solid tumors, leading to an improvement of progression free survival and overall survival in comparison to standard chemotherapy. However, across different solid malignancies, the immune-checkpoints inhibitors efficacy is limited to a relative small number of patients and, for this reason, the identification of positive or negative predictive biomarkers represents an urgent need. Despite the expression of PD-L1 was largely investigated in various malignancies, (i.e., melanoma, head and neck malignancies, urothelial and renal carcinoma, metastatic colorectal cancer, and pancreatic cancer) as a biomarker for ICB treatment-patients selection, it showed an important, but still imperfect, role as positive predictor of response only in nonsmall cell lung cancer (NSCLC). Importantly, other tumor and/or microenvironments related characteristics are currently under clinical evaluation, in combination or in substitution of PD–L1 expression. In particular, tumor-infiltrating immune cells, gene expression analysis, mismatch- repair deficiency, and tumor mutational landscape may play a central role in predicting clinical benefits of CTLA-4 and/or PD-1/PD-L1 checkpoint inhibitors. In this review, we will focus on the clinical evaluation of emerging biomarkers and how these may improve the naïve vision of a single- feature patients-based selection.

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Section: Patients Selection For Immunotherapy: the Role Of Geneticmentioning

confidence: 99%

Patients Selection for Immunotherapy in Solid Tumors: Overcome the Naïve Vision of a Single Biomarker

Signorelli

Giannatempo

Grazia

et al. 2019

BioMed Research International

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“…MSI patients have a high mutational burden which is associated with high levels of neo-antigen presentation. This in turn has been known to be associated with better response to anti-PD-1 therapy across non-GE tumor types (72). Therefore, PD-1 inhibition may be an attractive potential therapy for gastric cancer patients with mismatch repair deficiency or MSI status.…”

Section: Msimentioning

confidence: 97%

Current status of immunotherapy and immune biomarkers in gastro-esophageal cancers

Ammannagari¹,

Atasoy²

2018

J. Gastrointest. Oncol.

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Gastroesophageal (GE) cancers continue to be a significant cause of mortality globally. Despite therapeutic advances in oncology, the prognosis of advanced GE cancer remains exceedingly poor. Immunotherapy has caused a major paradigm shift in the field of oncology. Not all patients benefit from these agents and several studies are trying to identify predictive and prognostic biomarkers to better inform and guide treatment decisions. The potential role of immunotherapy in GE cancers is emerging. These cancer types are molecularly and immunologically heterogeneous, and this heterogeneity influences the tumor microenvironment posing a significant challenge to studying biomarkers of response to immunotherapy. Here in this article, we discuss the need for new therapeutic approaches in GE cancers, review the emerging data on the activity of checkpoint inhibitors and the role of biomarkers in this setting.

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“…[ 18 ] Pembrolizumab was assessed as a second or further line of treatment in patients with dMMR and MSI-H mCRC, where the KEYNOTE-164 trial achieved an objective response rate of 33% with a minority of its patients experiencing grade 3-4 adverse events (AEs) (13–16%). [ 19 ] Finally, the KEYNOTE-177 study tested pembrolizumab against fluorouracil-based chemotherapy in the first-line setting of mCRC, where duration of progression-free survival (PFS) improved by almost 100% (16.5 vs 8.2 months) and the incidence of grade 3 or higher treatment-related side effects dropped to one-third (22% vs 66%). [ 20 ] Overall, the results of these studies established a clear role for programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors in advanced stages of CRC; however, it was still unclear whether their role could be extended to earlier settings or RC alone.…”

Section: Immune Checkpoint Blockade In Crcmentioning

confidence: 99%

A Review of Scheduling Strategies for Radiotherapy and Immune Checkpoint Inhibition in Locally Advanced Rectal Cancer

Melissourgou-Syka,

Gillespie,

O'Cathail

et al. 2023

Journal of Immunotherapy and Precision Oncology

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Colorectal cancer (CRC) is the third most common malignancy across the globe and, despite advances in treatment strategies, survival rates remain low. Rectal cancer (RC) accounts for most of these cases, and traditional management strategies for advanced disease include total neoadjuvant therapy (TNT) with chemoradiotherapy followed by curative surgery. Unfortunately, approximately 10–15% of patients have no response to treatment or have recurrence at a short interval following radiotherapy. The introduction of immunotherapy in the form of immune checkpoint blockade (ICB) in metastatic colorectal cancer has improved clinical outcomes, yet most patients with RC present with microsatellite stable disease, which lacks the immune-rich microenvironment where ICB is most effective. There is evidence that combining radiotherapy with ICB can unlock the mechanisms that drive resistance in patients; however, the sequencing of these therapies is still debated. This review offers a comprehensive overview of clinical trials and preclinical models that use radiotherapy–immunotherapy combinations in RC in an attempt to extrapolate the ideal sequencing of the two treatment modalities. The results highlight the dearth of evidence to answer the question of whether ICB should be given before, during, or after radiotherapy, yet it is suggested that improving the relevance of our preclinical models will provide a platform with higher translational value and will lead to appropriate clinical trial designs.

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KEYNOTE-164: Phase 2 study of pembrolizumab for patients with previously treated, microsatellite instability-high advanced colorectal carcinoma.

Cited by 5 publications

References 0 publications

Patients Selection for Immunotherapy in Solid Tumors: Overcome the Naïve Vision of a Single Biomarker

Patients Selection for Immunotherapy in Solid Tumors: Overcome the Naïve Vision of a Single Biomarker

Current status of immunotherapy and immune biomarkers in gastro-esophageal cancers

A Review of Scheduling Strategies for Radiotherapy and Immune Checkpoint Inhibition in Locally Advanced Rectal Cancer

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