Targeted oncology
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Idelalisib (Zydelig®) is a first-in-class, orally administered, phosphatidylinositol 3-kinase-δ inhibitor that was recently approved for the treatment of relapsed chronic lymphocytic leukaemia (CLL), relapsed follicular B-cell non-Hodgkin's lymphoma (NHL) and relapsed small lymphocytic lymphoma (SLL) in the USA and for the treatment of CLL and refractory follicular lymphoma in the EU. In a pivotal phase III trial in patients with relapsed CLL who were not able to receive cytotoxic agents, recipients of idelalisib plus rituximab had significantly improved progression-free survival, overall survival, overall response and lymph node response, compared with recipients of placebo plus rituximab. ⋯ Oral idelalisib had a generally manageable adverse event profile, although episodes of serious/fatal diarrhoea or colitis, hepatotoxicity, pneumonitis and intestinal perforation were reported. In conclusion, idelalisib represents an important advance in the treatment of relapsed CLL and relapsed indolent NHL.
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Review
The success story of trastuzumab emtansine, a targeted therapy in HER2-positive breast cancer.
Trastuzumab emtansine is a unique antibody-drug conjugate targeting selectively human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells, thus conferring high efficacy with minimal systemic toxicities. Trastuzumab emtansine consists of a monoclonal antibody trastuzumab and potent cytotoxic agent DM1, combined together through a stable thioether bond. First-in-man phase I study set the maximum tolerated dose at 3.6 mg/kg given intravenously on a 3-weekly regimen. ⋯ Cardiotoxicity, frequently observed in HER2-directed therapy, was not reported. Although thrombocytopenia and elevations in hepatic enzymes were reported with trastuzumab emtansine, these events were reversible and manageable. Ongoing trials investigating trastuzumab emtansine as a single-agent or in combination with other agents, will determine the place of trastuzumab emtansine in the current therapeutic strategies deployed for HER2-metastatic breast cancer.
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Review Meta Analysis
The predictive role of skin rash with cetuximab and panitumumab in colorectal cancer patients: a systematic review and meta-analysis of published trials.
Skin rash is an early and frequent phenomenon during treatment with anti-epidermal growth factor receptor monoclonal antibodies. The objective of this review is to assess the predictive value of skin rash in patients with advanced colorectal cancer treated with cetuximab and panitumumab. We searched PubMed and ASCO Meetings for publications reporting the correlation of skin rash with survival and/or response rate. ⋯ Similarly, patients who developed moderate or severe rash had an increased chance of response (35 vs 13%; RR 2.23, p<0.00001). The occurrence of skin rash during treatment with cetuximab and panitumumab represents a significant predictor of the efficacy of these drugs. The hypothesis that, in patients who lack substantial skin toxicity, this treatment is not beneficial and requires early discontinuation deserves further study.
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Review Meta Analysis
The predictive role of skin rash with cetuximab and panitumumab in colorectal cancer patients: a systematic review and meta-analysis of published trials.
Skin rash is an early and frequent phenomenon during treatment with anti-epidermal growth factor receptor monoclonal antibodies. The objective of this review is to assess the predictive value of skin rash in patients with advanced colorectal cancer treated with cetuximab and panitumumab. We searched PubMed and ASCO Meetings for publications reporting the correlation of skin rash with survival and/or response rate. ⋯ Similarly, patients who developed moderate or severe rash had an increased chance of response (35 vs 13%; RR 2.23, p<0.00001). The occurrence of skin rash during treatment with cetuximab and panitumumab represents a significant predictor of the efficacy of these drugs. The hypothesis that, in patients who lack substantial skin toxicity, this treatment is not beneficial and requires early discontinuation deserves further study.
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In patients with advanced non-small cell lung cancer (NSCLC), the benefit-to-risk ratio of doublet-targeted agents versus single agent is not clear. A systematic review and quantitative meta-analysis were, therefore, undertaken to evaluate the available evidence from randomized trials. This study aims to evaluate the efficacy and safety of erlotinib versus doublets (erlotinib plus another targeted agent) in advanced NSCLC and, if adequate data are available, to investigate whether or not predefined patient groups benefit more or less from doublet-targeted therapy based on erlotinib. ⋯ The benefit-to-risk ratio of doublets in advanced NSCLC may be more favorable than that of single-agent. The results of this systematic review suggest that patients with advanced NSCLC might benefit from doublet-targeted therapy based on erlotinib compared to erlotinib alone. However, an individual patient data systematic review and meta-analysis are needed to give us a more reliable assessment of the size of benefits and to explore whether doublet therapy may be more or less effective for particular types of patients.