Targeted oncology
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Review Meta Analysis
Prognostic Role of Programmed Death Ligand-1 Expression in Breast Cancer: A Systematic Review and Meta-Analysis.
Cancer therapies that target the PD-1/PD-L1 pathway are in ongoing phase I/II clinical trials for several tumor types. However, the prognostic value of PD-L1 expression in breast cancer is unclear. ⋯ In breast cancer, high PD-L1 protein expression appears to be a negative prognostic factor, whereas high PD-L1 mRNA expression appears to be a favorable prognostic factor.
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Review Meta Analysis
Prognostic Role of Programmed Death Ligand-1 Expression in Breast Cancer: A Systematic Review and Meta-Analysis.
Cancer therapies that target the PD-1/PD-L1 pathway are in ongoing phase I/II clinical trials for several tumor types. However, the prognostic value of PD-L1 expression in breast cancer is unclear. ⋯ In breast cancer, high PD-L1 protein expression appears to be a negative prognostic factor, whereas high PD-L1 mRNA expression appears to be a favorable prognostic factor.
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Afatinib (Giotrif®, Gilotrif®) is an orally administered, irreversible inhibitor of the ErbB family of tyrosine kinases. In the first-line treatment of patients with advanced lung adenocarcinoma with activating epidermal growth factor receptor (EGFR) mutations, afatinib significantly prolonged progression-free survival (PFS) and time to treatment failure (TTF), but not overall survival (OS), compared with gefitinib (LUX-Lung 7 trial). In the overall population of patients receiving first-line treatment for advanced lung adenocarcinoma with activating EGFR mutations, afatinib significantly prolonged PFS, but not OS, compared with pemetrexed plus cisplatin (LUX-Lung 3 trial) or gemcitabine plus cisplatin (LUX-Lung 6 trial). ⋯ In the second-line treatment of advanced squamous non-small cell lung cancer (NSCLC), afatinib significantly prolonged PFS and OS, compared with erlotinib, regardless of EGFR mutation status (LUX-Lung 8 trial). Afatinib had a predictable and manageable tolerability profile in patients with advanced NSCLC. In conclusion, afatinib is an important option for the first-line treatment of patients with advanced NSCLC and activating EGFR mutations, and provides an additional option for the treatment of patients with squamous NSCLC that has progressed following first-line platinum-based chemotherapy.
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The BRAF inhibitor dabrafenib (Tafinlar(®)) and the MEK inhibitor trametinib (Mekinist(®)) are indicated, as monotherapy or in combination with each other, for the treatment of patients with unresectable or metastatic melanoma with a BRAF (V600) mutation. This article reviews the therapeutic efficacy and tolerability of combination treatment with dabrafenib and trametinib in this indication and summarizes relevant pharmacological data. Dabrafenib plus trametinib significantly prolonged progression-free survival (PFS) and overall survival (OS), improved objective response rates (ORRs) and preserved health-related quality of life (HR-QOL) to a greater extent than dabrafenib (in the double-blind COMBI-d study) and vemurafenib (in the open-label COMBI-v study) in two large, randomized, phase III studies in treatment-naïve patients with unresectable or metastatic melanoma with BRAF (V600E/K) mutation. ⋯ Combination therapy did not increase overall toxicity relative to dabrafenib or vemurafenib monotherapy, with most adverse events (AEs) mild or moderate in severity and generally manageable. Fewer skin-related AEs (e.g. cutaneous malignancies, hyperkeratinosis and hand-foot syndrome) were reported with combination therapy than with dabrafenib or vemurafenib, probably because of reduced paradoxical activation of the MAPK pathway. Thus, dabrafenib plus trametinib provides an important treatment option for patients with BRAF (V600) mutation-positive unresectable or metastatic melanoma.
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Oral panobinostat (Farydak®), a potent nonselective histone deacetylase inhibitor, is approved in several countries for use in combination with bortezomib and dexamethasone in patients with multiple myeloma (MM) [USA] or relapsed and/or refractory MM (EU) who have received at least two prior treatment regimens, including bortezomib and an immunomodulatory drug (IMiD). In a pivotal phase III trial (PANORAMA 1) in patients with relapsed or relapsed and refractory MM who had received one to three previous lines of therapy, progression-free survival (PFS) was significantly prolonged with panobinostat plus bortezomib and dexamethasone compared with placebo plus bortezomib and dexamethasone. ⋯ Panobinostat plus bortezomib and dexamethasone had a generally manageable tolerability profile, with the most frequent grade 3-4 adverse events being myelosuppression, diarrhoea, asthenia or fatigue, peripheral neuropathy and pneumonia. Thus, panobinostat, in combination with bortezomib and dexamethasone, is a useful addition to the available treatment options for patients with relapsed or refractory MM.