Keytruda for Mesothelioma Flops in Phase III Clinical Trial

Results from a phase III clinical trial comparing Keytruda (pembrolizumab) to standard chemotherapy shows the immunotherapy drug still has a long way to go as a viable treatment option for malignant pleural mesothelioma. Keytruda did not improve progression-free survival for mesothelioma patients who progressed after first-line chemotherapy. The disappointing results from the PROMISE-meso study were presented at the European Society of Medical Oncology (ESMO) annual meeting last week. It was the first randomized trial comparing progression-free survival between immunotherapy and first-line chemotherapy for mesothelioma patients. Nearly four times more patients responded to the Keytruda over chemotherapy. However, these responses did not delay tumor progression or improve survival. “Despite correcting for crossover, an overall survival benefit was not observed,” Dr. Sanjay Popat of Royal Marsden Hospital in London said at ESMO. “The pembrolizumab safety profile was consistent with that previously observed. Further exploratory translational work is ongoing to identify subgroups that could benefit from pembrolizumab.” Chemotherapy Showed Longer Progression-Free Survival The progression-free survival for patients treated with Keytruda was just 2.5 months, compared to 3.4 months with standard chemotherapy regimens. Median overall survival did not change significantly between the two groups. A combination of Alimta (pemetrexed) and platinum-based chemo...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news

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Although mesothelioma is the consequence of a protracted immune response to asbestos fibers and characterized by a clear immune infiltrate, novel immunotherapy approaches show less convincing results as compared to those seen in melanoma and non-small cell lung cancer. The immune suppressive microenvironment in mesothelioma is likely contributing to this therapy resistance. Therefore, it is important to explore the characteristics of the tumor microenvironment for explanations for this recalcitrant behavior. This review describes the stromal, cytokine, metabolic, and cellular milieu of mesothelioma, and attempts to make co...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
(Impact Journals LLC) Cryopreserved cell-free PE fluid from 101 NSCLC patients, 8 mesothelioma and 13 with benign PE was assayed for a panel of 40 cytokines/chemokines using the Luminex system. Comparing NSCLC PE and published plasma levels of CAR-T recipients, both were dominated by sIL-6R and IL-6 but NSCLC PE had more VEGF, FGF2 and TNF, and less IL-2, IL-4, IL-13, IL-15, MIP1 and IFN.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Conditions:   Non Small Cell Lung Cancer;   Non-squamous Non-small-cell Lung Cancer;   Urothelial Carcinoma;   Malignant Mesothelioma Interventions:   Drug: Cabozantinib;   Drug: Pemetrexed Sponsor:   Augusta University Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Introduction: Malignant pleural mesothelioma (MPM) is a rare disease with poor prognosis. Previous preclinical studies have shown that activin A is overexpressed in MPM and this overexpression is associated with cancer cachexia and resistance to platinum-based chemotherapy. We evaluated circulating activin levels and its endogenous antagonist follistatin/FSTL3 in thoracic malignancy.Methods: Patients suspected of thoracic malignancy were prospectively recruited prior to either diagnostic or therapeutic surgery. Serum samples were collected from 21 patients with MPM, 59 patients with non-small-cell lung cancer (NSCLC), 22 p...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Pleural and mediastinal malignancies Source Type: research
Authors: Donnenberg AD, Luketich JD, Donnenberg VS Abstract INTRODUCTION: We compared the secretome of metastatic (non-small cell lung cancer (NSCLC)) and primary (mesothelioma) malignant pleural effusions, benign effusions and the published plasma profile of patients receiving chimeric antigen receptor T cells (CAR-T), to determine factors unique to neoplasia in pleural effusion (PE) and those accompanying an efficacious peripheral anti-tumor immune response. MATERIALS AND METHODS: Cryopreserved cell-free PE fluid from 101 NSCLC patients, 8 mesothelioma and 13 with benign PE was assayed for a panel of 40 cytok...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Nivolumab is a fully human, immunoglobulin G4 (kappa) isotype monoclonal antibody that binds programmed cell death protein 1 (PD-1) on activated immune cells and disrupts the engagement of the receptor with its ligands programmed death-ligand 1 (PD-L1: B7-H1/CD274 and PD-L2: B7-DC/CD273), thereby abrogating inhibitory signals and augmenting the antitumor response of the host [1]. In previous clinical trials, nivolumab has shown activity in several tumor types, including melanoma, renal cell carcinoma, non-small cell lung cancer (NSCLC), hodgkin lymphoma, and malignant pleural mesothelioma.
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
This study aimed to investigate the feasibility of fitting dual-input tracer kinetic models to DCE-MRI datasets of thoracic malignancies, including malignant pleural mesothelioma (MPM) and nonsmall cell lung cancer (NSCLC), by comparing them to single-input (pulmonary or systemic arterial input) tracer kinetic models for the voxel-level analysis within the tumor with respect to goodness-of-fit statistics. Fifteen patients (five MPM, ten NSCLC) underwent DCE-MRI prior to radiotherapy. DCE-MRI data were analyzed using five different single- or dual-input tracer kinetic models: Tofts-Kety (TK), extended TK (ETK), two compartm...
Source: Journal of Applied Clinical Medical Physics - Category: Physics Authors: Tags: J Appl Clin Med Phys Source Type: research
This study quantifies the disturbing trend that, despite the expansion in the number of patients eligible for expensive and potentially toxic ICIs [immune checkpoint inhibitors], the ratio of those benefiting is decreasing,” wrote Dr. Daniel V.T. Catenacci, co-author of an editorial that accompanied the study in JAMA Network. “Observations in this article are sobering and remind us to keep expectations realistic.” Both Catenacci and Haslem agreed that the study should serve as a reminder to patients, physicians and policy makers to have more realistic discussions about the use of, and expectations of, the...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Researchers at Osaka University in Japan have identified a key component of physical health associated with response to immunotherapy drugs. Among people with non-small cell lung cancer, higher levels of muscle mass predicted a better response to PD-1 inhibitor immunotherapy. Sarcopenia — the term used to describe low muscle mass levels — appears to reduce the benefits a person receives from immunotherapy cancer treatment. “Sarcopenia at baseline is a significant predictor of worse outcome in patients with advanced NSCLC [non-small cell lung cancer] receiving PD-1 blockade,” the study investigators ...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Doctors in China may have uncovered an effective second- or third-line treatment option for patients with malignant pleural mesothelioma. Dr. RongQin Meng, an oncologist at 363 Hospital in Cheng Du, said the investigational drug Apatinib (rivoceranib) could become part of a much-needed advance in mesothelioma treatment. After first- and second-line chemotherapy combinations had failed to slow tumor growth in a 58-year-old woman, Apatinib provided a five-month progression-free survival. “I was surprised at the result,” Meng told The Mesothelioma Center at Asbestos.com. “After taking the drug, the quality o...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
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