Search results for "pembrolizumab"
showing 10 items of 43 documents
New-onset third-degree atrioventricular block because of autoimmune-induced myositis under treatment with anti-programmed cell death-1 (nivolumab) fo…
2017
There has been considerable progress in treating malignant melanoma over the last few years. The immune-checkpoint-inhibitors nivolumab and pembrolizumab have been approved by the Food and Drug Administration in 2014 for the therapy of metastatic melanoma. Anti-programmed cell death-1-blocking antibodies are known to cause immune-related adverse events. Physicians should be aware of common and rare side effects and pay attention to new ones. We therefore report a severe and life-threatening side effect of anti-programmed cell death-1 immunotherapy with nivolumab that has not been previously reported: the development of a third-degree atrioventricular block. After a second infusion with nivo…
Pembrolizumab in First-line Gastric Cancer: Win, Lose, or Draw?
2020
IMPORTANCE: Safe and effective therapies for untreated, advanced gastric/gastroesophageal junction (G/GEJ) cancer remain an unmet need. OBJECTIVE: To evaluate the antitumor activity of pembrolizumab, pembrolizumab plus chemotherapy, or chemotherapy alone in patients with untreated, advanced G/GEJ cancer with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or greater. DESIGN, SETTING, AND PARTICIPANTS: The phase 3 KEYNOTE-062 randomized, controlled, partially blinded interventional trial enrolled 763 patients with untreated, locally advanced/unresectable or metastatic G/GEJ cancer with PD-L1 CPS of 1 or greater from 200 centers in 29 countries between September 18, …
In the literature: April 2019
2019
Glioblastoma (GBM) remains an unmet need in Medical Oncology considering its poor prognosis and the lack of advances in therapeutics in more than one decade.1 Despite the initial enthusiasm, the development of immunotherapy in GBM has proved to be challenging, with a disappointing negative phase III clinical trial.2 Some of the phenotypic hallmarks of GBM make immunotherapy difficult. Its relatively low mutational load, its immunologically ‘cold’ microenvironment with scarce infiltrating immune effector cells, a dominant myeloid compartment composed by microglia and myeloid-derived suppressor cells and a strong immunosuppression, both local, mediated by immunosuppressive regulatory T cells …
Abstract OT-31-01: A phase II study to evaluate the efficacy and safety of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer: P…
2021
Abstract Background Considering the high proportion of tumor-infiltrating lymphocytes (TILs) in BRCA-related breast cancer, we expect that PD-1 pathway is highly expressed and PD-1 antagonist pembrolizumab could provide clinical activity in this kind of tumor. Furthermore, BRCA-related breast cancers are known to be more sensitive to platinum-derived drugs. Thus the association between Pembrolizumab and Carboplatin in metastatic BRCA-related breast cancer seems to be active in this setting of patients. This study will evaluate the safety and the efficacy of Pembrolizumab associated with Carboplatin in BRCA mutated or with unknown mutations metastatic breast cancer patients. Study and Statis…
Abstract CT282: KEYNOTE-975: A randomized, double-blind, placebo-controlled phase 3 trial of pembrolizumab vs placebo in participants with esophageal…
2020
Abstract Background: For patients with unresectable esophageal cancer (EC), definitive chemoradiotherapy (dCRT) is a standard treatment option. Platinum plus fluoropyrimidine-based regimens are comparable in dCRT and are considered standard options; however, overall survival (OS) is still poor, indicating a need for more effective therapies. The programmed cell death 1 inhibitor pembrolizumab showed promising response as third- and second-line monotherapy in patients with advanced, unresectable EC in the KEYNOTE-180 and KEYNOTE-181 studies, respectively. In the phase 3 KEYNOTE-181 trial, pembrolizumab extended OS vs chemotherapy in patients with a PD-L1 combined positive score (CPS) ≥10. KE…
In the literature: October 2018
2018
Several trials with the check-point inhibitors pembrolizumab or nivolumab demonstrated some antitumour efficacy in chemorefractory advanced gastric cancer with a response rate ranging from 10% to 26%. However, no clear predictive biomarkers were found to facilitate a proper selection of patients. A series of 61 patients with advanced gastric cancer received second-line or third-line treatment with pembrolizumab in a prospective phase 2 trial.1 In a cooperative effort carried out by Korean and American investigators, a molecular characterisation of all tumours was performed including whole-exome sequencing and RNA sequencing of tissue biopsies, as well as circulating tumour DNA (ctDNA) from …
In the literature: December 2018
2018
The current development of immune checkpoint modulatory treatments has shown durable responses in the treatment of multiple cancer types.1 However, predictive biomarkers beyond PD-1 ligand 1 (PD-L1) expression and high microsatellite instability (MSI-H) to stratify patients and identify those who could benefit of these therapies are needed. In this sense, a recent study published in Science by Cristescu et al 2 describes the potential usefulness of combining the tumour mutational burden (TMB) and the T cell-inflamed gene expression profile (GEP) to jointly predict clinical response to pembrolizumab. Both PD-L1 and the GEP represent a T cell-inflamed tumour microenvironment (TME), whereas TM…
116 Evaluation of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in cervical cancer: data from phase 1 and phase 2 studies
2021
Introduction/Background* The accelerated US Food and Drug Administration approval of pembrolizumab validated the efficacy of anti-PD-(L)1 therapy for patients with recurrent/metastatic cervical cancer; however, the objective response rate (ORR) with pembrolizumab was 14.3% in patients with PD-L1–expressing tumours. Human papillomavirus infection is implicated in >95% of cervical cancers and is linked to upregulation of TGF-β signalling. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β ‘trap’) fused to a human immunoglobulin G1 monoclonal antibody blocking PD-L1. We report pooled safety and efficacy in pati…
Programmed Death Ligand 1 (PD-L1) as a Predictive Biomarker for Pembrolizumab Therapy in Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC).
2019
Recently, immunotherapy has been shown to be an effective and helpful therapeutic option for the treatment of advanced non-small-cell lung cancer (NSCLC). The activity of antitumor T cells may be restored through the checkpoint blockade using anti-programmed death 1 or anti-programmed death ligand 1 (PD-L1) antibodies, showing, in several cancer patients, an increased progression-free survival and overall survival compared with classical chemotherapy. As recently shown by several studies, the PD-L1 expression levels in tumors may offer a selection criterion for patients to predict their immunotherapy response. In particular, NSCLC patients with high tumor PD-L1 levels (proportional score ≥ …
Role of Immunotherapy in the Management of Hepatocellular Carcinoma: Current Standards and Future Directions
2020
The multikinase inhibitor sorafenib was the only approved systemic therapy in advanced hepatocellular carcinoma (HCC) for about a decade. In recent years, the number of approved agents has increased significantly as a result of a number of positive phase iii clinical trials. Lenvatinib as a first-line treatment, and regorafenib, cabozantinib, and ramucirumab in the second-line setting are now approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency. In phase II studies, immunotherapy with nivolumab and monotherapy using pembrolizumab yielded impressive results for overall survival in therapy-naïve and pretreated patients, leading to the accelerated approval …