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dinsdag 18 juli 2017

The Lancet: [Articles] Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERM...

[Articles] Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial
Tremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma. The safety profile of tremelimumab was consistent with the known safety profile of CTLA-4 inhibitors. Investigations into whether immunotherapy combination regimens can provide greater efficacy than monotherapies in malignant mesothelioma are ongoing.
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[Comment] CTLA-4 blockade in mesothelioma: ineffective or reason for optimism?
Malignant pleural mesothelioma is an aggressive disease with a poor prognosis and few treatment options. The combination of pemetrexed and cisplatin is the only approved therapy for patients with unresectable disease.1 No therapies have been approved for mesothelioma that has progressed after this initial systemic therapy. The regulatory approval of antibodies blocking immune checkpoints that function as negative regulators of T-cell function—cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4), programmed death-1 (PD-1), and programmed death ligand 1 (PD-L1)—in several different cancers2 has prompted substantial interest in the clinical investigation of these agents for mesothelioma.
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[Comment] Reduced-dose ipilimumab with standard-dose pembrolizumab: is less more?
Many studies are testing whether or not the combination of additional drugs with anti-programmed death 1 (PD-1) agents will improve survival outcomes. Among these approaches, anti-PD-1 drugs in combination with the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor ipilimumab is furthest along in clinical development. Nivolumab (1 mg/kg) plus standard-dose ipilimumab (3 mg/kg) is approved by regulatory agencies for treatment of patients with advanced melanoma and increases overall survival, progression-free survival, and the proportion of patients who achieve an objective response compared with ipilimumab monotherapy.
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[Articles] Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial
The long-term findings of the TEAM trial confirm that both exemestane alone and sequential treatment with tamoxifen followed by exemestane are reasonable options as adjuvant endocrine therapy in postmenopausal patients with hormone receptor-positive early breast cancer. These results suggest that the opportunity to individualise adjuvant endocrine strategy accordingly, based on patient preferences, comorbidities, and tolerability might be possible.
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[Comment] Tuning up adjuvant endocrine therapy: the TEAM trial
The updated results of the TEAM trial, a randomised, open-label, phase 3 study1 comparing 5 years of exemestane with 2–3 years of tamoxifen followed by exemestane (up to a total of 5 years; sequential group) as adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer are reported in The Lancet Oncology by Marloes Derks and colleagues. The study was originally done in nine countries and enrolled 9779 patients.2 Updated outcomes were only available for 6120 patients from six of the countries (63% of the total population).
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