Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial

Zalcman, Gérard; Mazières, Julien; Margery, J.; Greillier, L.; Audigier-Valette, Clarisse; Moro-Sibilot, Denis; Molinier, Olivier; Corre, Romain; Monnet, I.; Gounant, V.; Rivière, F.; Janicot, Henri; Gervais, Radj; Locher, C.; Milleron, B.; Tran, Quan Hung; Lebitasy, Marie-Paule; Morin, Franck; Créveuil, Christian; Parienti, Jean‐Jacques; Scherpereel, Arnaud

doi:10.1016/s0140-6736(15)01238-6

Cited by 837 publications

(670 citation statements)

References 32 publications

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“…The study then expanded to a randomized, controlled, openlabel, phase III trial with 448 patients. The addition of bevacizumab to cisplatin and pemetrexed significantly increased overall survival to 18.8 months in patients who received bevacizumab, cisplatin, and pemetrexed (n=223) vs. 16.1 months in patients who received cisplatin and pemetrexed (n=225) (38). Based on this trial, consideration should be given to bevacizumab in front-line therapy with pemetrexed and cisplatin or carboplatin in clinical practice.…”

Section: Anti-angiogenic Therapymentioning

confidence: 87%

“…Anti-metabolites such as pemetrexed, raltitrexed, and methotrexate, platinum analogs (cisplatin and carboplatin), gemcitabine, vinorelbine, and doxorubicin have activity in MPM with single-agent response rates of 7-20% (36). Anti-folate therapy with pemetrexed, combined with platinum therapy, with or without bevacizumab, is the current standard first-line systemic therapy for advanced or unresectable MPM (37,38).…”

Section: Cytotoxic Chemotherapy For Mpmmentioning

confidence: 99%

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Novel systemic therapy against malignant pleural mesothelioma

Mancuso

Neal

2017

Transl. Lung Cancer Res.

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Malignant pleural mesothelioma is an aggressive tumor of the pleura with an overall poor prognosis. Even with surgical resection, for which only a subset of patients are eligible, long term disease free survival is rare. Standard first-line systemic treatment consists of a platinum analog, an anti-metabolite, and sometimes anti-angiogenic therapy, but there is currently no well-established standard therapy for refractory or relapsed disease. This review focuses on efforts to develop improved systemic therapy for the treatment of malignant pleural mesothelioma (MPM) including cytotoxic systemic therapy, a variety of tyrosine kinase inhibitors and their downstream effector pathways, pharmacologic targeting of the epigenome, novel approaches to target proteins expressed on mesothelioma cells (such as mesothelin), arginine depletion therapy, and the emerging role of immunotherapy. Overall, these studies demonstrate the challenges of improving systemic therapy for MPM and highlight the need to develop therapeutic strategies to control this disease.

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Section: Anti-angiogenic Therapymentioning

confidence: 87%

Section: Cytotoxic Chemotherapy For Mpmmentioning

confidence: 99%

Novel systemic therapy against malignant pleural mesothelioma

Mancuso

Neal

2017

Transl. Lung Cancer Res.

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“…Cisplatin-pemetrexed was associated with an improvement in survival of 2.8 months compared to cisplatin alone in a large multicenter randomized trial (10). More recently, a large randomized trial conducted in France with 448 patients demonstrated that the addition of bevacizumab to cisplatin-pemetrexed provided an additional benefit of 2.7 months over cisplatin-pemetrexed and this triplet combination is now used as a possible first-line treatment for unresectable MPM in appropriately selected patients (11).…”

Section: Standard Of Care In Mpmmentioning

confidence: 99%

Radio-immunotherapy and chemo-immunotherapy as a novel treatment paradigm in malignant pleural mesothelioma

Perrot

2017

Transl. Lung Cancer Res.

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“…3 Recently, addition of bevacizumab to the chemotherapy-backbone showed a positive effect on survival. 4 Extensive investigation of the effects of implementation of radiotherapy and/or debulking surgery in standard treatment revealed variable success, but only when applied to select patient subgroups. 1,5–7 …”

Section: Introductionmentioning

confidence: 99%

Low-dose cyclophosphamide depletes circulating naïve and activated regulatory T cells in malignant pleural mesothelioma patients synergistically treated with dendritic cell-based immunotherapy

et al. 2018

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Rationale: Regulatory T cells (Treg) play a pivotal role in the immunosuppressive tumor micro-environment in cancer, including mesothelioma. Recently, the combination of autologous tumor lysate-pulsed dendritic cells (DC) and metronomic cyclophosphamide (mCTX) was reported as a feasible and well-tolerated treatment in malignant pleural mesothelioma patients and further as a method to reduce circulating Tregs.Objectives: The aim of this study was to establish the immunological effects of mCTX alone and in combination with DC-based immunotherapy on circulating Treg and other T cell subsets in mesothelioma patients.Methods: Ten patients received mCTX and DC-based immunotherapy after chemotherapy (n = 5) or chemotherapy and debulking surgery (n = 5). Peripheral blood mononuclear cells before, during and after treatment were analyzed for various Treg and other lymphocyte subsets by flow cytometry.Results: After one week treatment with mCTX, both activated FoxP3hi and naïve CD45RA+ Tregs were effectively decreased in all patients. In addition, a shift from naïve and central memory towards effector memory and effector T cells was observed. Survival analysis showed that overall Treg levels before treatment were not correlated with survival, however, nTreg levels before treatment were positively correlated with survival. After completion of mCTX and DC-based immunotherapy treatment, all cell subsets returned to baseline levels, except for the proportions of proliferating EM CD8 T cells, which increased.Conclusions: mCTX treatment effectively reduced the proportions of circulating Tregs, both aTregs and nTregs, thereby favoring EM T cell subsets in mesothelioma patients. Interestingly, baseline levels of nTregs were positively correlated to overall survival upon complete treatment.

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Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial

Cited by 837 publications

References 32 publications

Novel systemic therapy against malignant pleural mesothelioma

Novel systemic therapy against malignant pleural mesothelioma

Radio-immunotherapy and chemo-immunotherapy as a novel treatment paradigm in malignant pleural mesothelioma

Low-dose cyclophosphamide depletes circulating naïve and activated regulatory T cells in malignant pleural mesothelioma patients synergistically treated with dendritic cell-based immunotherapy

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