Chemotherapy for malignant pleural mesothelioma (original) (raw)
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Journal of Cancer Metastasis and Treatment, 2021
Patients with unresectable malignant pleural mesothelioma (MPM) have historically poor outcomes and treatment, and their treatments have been limited to palliative chemotherapy. Recent efforts to improve prognosis for these patients by adding angiogenesis inhibitors to chemotherapy led to significant benefits. However, the emergence of immunotherapy combinations for the front-line treatment has upended the standard of care and has led to the first new FDA approvals for the treatment of MPM in nearly two decades. This review aims to cover the main clinical trials in unresectable MPM with VEGF inhibitors and immunotherapy which have led to paradigm shifts in current practice. Ongoing clinical trials exploring the combination of chemo and immunotherapies show a great deal of promise, and continued support for ambitious, large-scale well-designed trials remain vital for defining the future outcomes of patients diagnosed with MPM.
Molecular and Clinical Oncology, 2022
Malignant pleural mesothelioma (MPM) is considered a relatively uncommon disease but its incidence is increasing worldwide. Patients affected by MPM have a very severe prognosis and have been often occupationally and environmentally exposed to asbestos. In recent years, checkpoint inhibitors have dramatically revolutionized the paradigm for the treatment of several malignancies. Several efforts have also been made to improve the survival outcomes of patients with MPM and after decades, the standard-of-care systemic treatment for unresectable MPM, based on first-line combination chemotherapy with cisplatin and pemetrexed, has changed. In addition to checkpoint inhibitors, other types of treatments, such as molecularly targeted therapy have been evaluated. However, to date, the results of these investigations are not very encouraging. The aim of the present review is to provide a comprehensive overview of the most relevant data of clinical trials regarding recent treatment strategies of MPM with a particular focus on immunotherapeutic and targeted approaches. Contents 1. Introduction 2. Malignant pleural mesothelioma (MPM) 3. Immunotherapy 4. Targeted agents in MPM 5. Conclusion
Biomarker-guided targeted and immunotherapies in malignant pleural mesothelioma
Therapeutic Advances in Medical Oncology
Malignant pleural mesothelioma (MPM) is a lethal thoracic malignancy whose incidence is still increasing worldwide. MPM is characterized by frequent inactivation of tumor-suppressor genes (TSGs), e.g., the homozygous deletion of CDKN2A/2B and various genetic alterations that inactivate BAP1, NF2, LATS1/2, and TP53. The leading cause for the poor prognosis of patients with MPM is the lack of effective treatment options, with conventional chemotherapy being the standard of care in the clinic, which has remained unchanged for almost 20 years. Precision oncology, a burgeoning effort to provide precise cancer treatment tailored to unique molecular changes in individual patients, has made tremendous progress in the last decade in several cancers, but not in MPM. Recent studies indicate a high degree of tumor heterogeneity in MPM and the importance to optimize histological and molecular classifications for improved treatment. In this review, we provide an up-to-date overview of recent adva...
Cancer Management and Research, 2015
Malignant pleural mesothelioma (MPM) is a rare tumor that is challenging to control. Despite some benefit from using the multimodality-approach (surgery, combination chemotherapy and radiation), survival remains poor. However, current research produced a list of potential therapies. Here, we summarize significant new preclinical and early clinical developments in treatment of MPM, which include mesothelin specific antibody and toxin therapies, interleukin-4 (IL-4) receptor toxins, dendritic cell vaccines, immune checkpoint inhibitors, and gene-based therapies. In addition, several local modalities such as photodynamic therapy, postoperative lavage using betadine, and cryotherapy for local recurrence, have also shown to be effective for local control of disease.
Current Challenges in Thoracic Surgery
Malignant pleural mesothelioma is a rare but extremely lethal disease for which there is no single curative therapy. Given this, a significant lack of consensus exists regarding optimal treatment strategies. Patients typically present late in the course of their disease, which has led many to advocate for palliative approaches to therapy, while others believe that macroscopic resection of disease in conjunction with multimodal therapy is preferable in highly selected individuals. Surgical strategies have recently evolved from the maximally invasive extrapleural pneumonectomy (EPP) to the more conservative extended pleurectomy and decortication. The addition of chemotherapy and radiotherapy to surgical interventions have allowed to extend progression-free survival, but this is still measured in months rather than years. Moreover, there is a lack of high-quality evidence to support all interventions, leading to variations in guidelines regarding trimodal therapy and a paucity of data demonstrating superiority of a single approach to care. Given this, new and promising treatment options are emerging which may allow to better control and treat malignant pleural mesothelioma. These include immunotherapy, virotherapy, T-cell therapies, and vaccines, among others. This paper therefore aims to give a comprehensive overview of current available treatments with a focus on surgical and trimodal therapies, as well as emerging treatment options for malignant pleural mesothelioma.
Progress in the Management of Malignant Pleural Mesothelioma in 2017
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2018
Malignant pleural mesothelioma (MPM) is an uncommon, almost universally fatal, asbestos-induced malignancy. New and effective strategies for diagnosis, prognostication, and treatment are urgently needed. Herein we review the advances in MPM achieved in 2017. Whereas recent epidemiological data demonstrated that the incidence of MPM-related death continued to increase in United States between 2009 and 2015, new insight into the molecular pathogenesis and the immunological tumor microenvironment of MPM, for example, regarding the role of BRCA1 associated protein 1 and the expression programmed death receptor ligand 1, are highlighting new potential therapeutic strategies. Furthermore, there continues to be an ever-expanding number of clinical studies investigating systemic therapies for MPM. These trials are primarily focused on immunotherapy using immune checkpoint inhibitors alone or in combination with other immunotherapies and nonimmunotherapies. In addition, other promising targe...
Immunotherapeutic Approaches in Malignant Pleural Mesothelioma
Cancers, 2021
Malignant pleural mesothelioma (MPM) is a rare and aggressive malignant disease affecting the mesothelium, commonly associated to asbestos exposure. The current therapeutic actions, based on cisplatin/pemetrexed treatment, are limited due to the late stage at which most patients are diagnosed and to the intrinsic chemo-resistance of the tumor. Another relevant point is the absence of approved therapies in the second line setting following progression of MPM after chemotherapy. Considering the poor prognosis of the disease and the fact that the incidence of this tumor is expected to increase in the next decade, novel therapeutic approaches are urgently needed. In the last few years, several studies have investigated the efficacy and safety of immune-checkpoint inhibitors (ICIs) in the treatment of unresectable advanced MPM, and a number of trials with immunotherapeutic agents are ongoing in both first line and second line settings. In this review, we describe the most promising emerg...
Chemotherapy for malignant pleural mesothelioma: past results and recent developments
Lung Cancer, 2004
This review summarises the results of previously conducted clinical trials, and subsequently presents data arising from all phase II-III studies on chemotherapy of malignant pleural mesothelioma (MPM) published since the last relevant overview. While response rates exceeding 30% have barely been achieved with established cytotoxic drugs in MPM therapy, novel chemotherapeutic agents and their combinations appear more promising. This applies especially to the antimetabolites, and in particular to pemetrexed that produced response rates of up to 45% in combination with platinum compounds. Raltitrexed combined with oxaliplatin has also been shown to be effective, and gemcitabine-applied as a single agent or in combination with cisplatin-as well as vinorelbine appear to improve the quality of life in patients presenting with MPM. Data can now be more precisely analysed by increasingly implemented randomised studies, applying a standardised staging system, and distinguishing prognostic groups. While chemotherapy for MPM remains a challenging task, important steps have clearly been made in the past years to combat this aggressive disease. The publication of pemetrexed with cisplatin phase III results in a peer-reviewed journal may soon establish a standard of care.
The Lancet, 2016
Background Malignant pleural mesothelioma is an aggressive cancer with poor prognosis, linked to occupational asbestos exposure. Vascular endothelial growth factor is a key mitogen for malignant pleural mesothelioma cells, therefore targeting of vascular endothelial growth factor might prove eff ective. We aimed to assess the eff ect on survival of bevacizumab when added to the present standard of care, cisplatin plus pemetrexed, as fi rst-line treatment of advanced malignant pleural mesothelioma. Methods In this randomised, controlled, open-label, phase 3 trial, we recruited patients aged 18-75 years with unresectable malignant pleural mesothelioma who had not received previous chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0-2, had no substantial cardiovascular comorbidity, were not amenable to curative surgery, had at least one evaluable (pleural eff usion) or measurable (pleural tumour solid thickening) lesion with CT, and a life expectancy of >12 weeks from 73 hospitals in France. Exclusion criteria were presence of central nervous system metastases, use of antiaggregant treatments (aspirin ≥325 mg per day, clopidogrel, ticlopidine, or dipyridamole), anti-vitamin K drugs at a curative dose, treatment with low-molecular-weight heparin at a curative dose, and treatment with non-steroidal anti-infl ammatory drugs. We randomly allocated patients (1:1; minimisation method used [random factor of 0•8]; patients stratifi ed by histology [epithelioid vs sarcomatoid or mixed histology subtypes], performance status score [0-1 vs 2], study centre, or smoking status [never smokers vs smokers]) to receive intravenously 500 mg/m² pemetrexed plus 75 mg/m² cisplatin with (PCB) or without (PC) 15 mg/kg bevacizumab in 21 day cycles for up to six cycles, until progression or toxic eff ects. The primary outcome was overall survival (OS) in the intention-to treat population. Treatment was open label. This IFCT-GFPC-0701 trial is registered with ClinicalTrials.gov, number NCT00651456. Findings From Feb 13, 2008, to Jan 5, 2014, we randomly assigned 448 patients to treatment (223 [50%] to PCB and 225 [50%] to PC). OS was signifi cantly longer with PCB (median 18•8 months [95% CI 15•9-22•6]) than with PC (16•1 months [14•0-17•9]; hazard ratio 0•77 [0•62-0•95]; p=0•0167). Overall, 158 (71%) of 222 patients given PCB and 139 (62%) of 224 patients given PC had grade 3-4 adverse events. We noted more grade 3 or higher hypertension (51 [23%] of 222 vs 0) and thrombotic events (13 [6%] of 222 vs 2 [1%] of 224) with PCB than with PC. Interpretation Addition of bevacizumab to pemetrexed plus cisplatin signifi cantly improved OS in malignant pleural mesothelioma at the cost of expected manageable toxic eff ects, therefore it should be considered as a suitable treatment for the disease. Funding Intergroupe Francophone de Cancérologie Thoracique (IFCT).
Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future
Frontiers in Oncology
Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the pleural surface associated with asbestos exposure. The median survival of MPM patients is a mere 8-14 months, and there are few biomarkers and no cure available. It is hoped that, eventually, the incidence of MPM will drop and remain low and constant, given that most nations have banned the use of asbestos, but in the meantime, the incidence in Europe is still growing. The exact molecular mechanisms that explain the carcinogenicity of asbestos are not known. Standard therapeutic strategies for MPM include surgery, often coupled with chemotherapy and/or radiotherapy, in a small percentage of eligible patients and chemotherapy in tumors considered unresectable with or without adjuvant radiotherapy. In recent years, several new therapeutic avenues are being explored. These include angiogenesis inhibitors, synthetic lethal treatment, miRNA replacement, oncoviral therapies, and the fast-growing field of immunotherapy alone or in combination with chemotherapy. Of particular promise are the multiple options offered by immunotherapy: immune checkpoint inhibitors, tumor vaccines, and therapies taking advantage of tumor-specific antigens, such as specific therapeutic antibodies or advanced cell-based therapies exemplified by the CART cells. This review comprehensively presents both old and new therapeutic options in MPM, focusing on the results of the numerous recent and ongoing clinical trials in the field, including the latest data presented at international meetings (AACR, ASCO, and ESMO) this year, and concludes that more work has to be done in the framework of tailored therapies to identify reliable targets and novel biomarkers to impact MPM management.