Journal of clinical oncology : official journal of the American Society of Clinical Oncology
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Randomized Controlled Trial Multicenter Study Comparative Study
Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of Onartuzumab Plus Bevacizumab Versus Placebo Plus Bevacizumab in Patients With Recurrent Glioblastoma: Efficacy, Safety, and Hepatocyte Growth Factor and O6-Methylguanine-DNA Methyltransferase Biomarker Analyses.
Purpose Bevacizumab regimens are approved for the treatment of recurrent glioblastoma in many countries. Aberrant mesenchymal-epithelial transition factor (MET) expression has been reported in glioblastoma and may contribute to bevacizumab resistance. The phase II study GO27819 investigated the monovalent MET inhibitor onartuzumab plus bevacizumab (Ona + Bev) versus placebo plus bevacizumab (Pla + Bev) in recurrent glioblastoma. ⋯ Grade ≥ 3 adverse events were reported in 38.5% of patients who received Ona + Bev and 35.9% of patients who received Pla + Bev. Exploratory biomarker analyses suggested that patients with high expression of hepatocyte growth factor or unmethylated O6-methylguanine-DNA methyltransferase may benefit from Ona + Bev. Conclusion There was no evidence of further clinical benefit with the addition of onartuzumab to bevacizumab compared with bevacizumab plus placebo in unselected patients with recurrent glioblastoma in this phase II study; however, further investigation into biomarker subgroups is warranted.
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Randomized Controlled Trial Comparative Study
Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2-Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study.
Purpose Trastuzumab and pertuzumab are human epidermal growth factor receptor 2 (HER2) -targeted monoclonal antibodies, and trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that combines the properties of trastuzumab with the cytotoxic activity of DM1. T-DM1 demonstrated encouraging efficacy and safety in a phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Combination T-DM1 and pertuzumab showed synergistic activity in cell culture models and had an acceptable safety profile in a phase Ib and II study. ⋯ The incidence of grade ≥ 3 adverse events was numerically higher in the control arm (54.1%) versus the T-DM1 arm (45.4%) and T-DM1 plus pertuzumab arm (46.2%). Numerically fewer patients discontinued treatment because of adverse events in the T-DM1 arms, and health-related quality of life was maintained for longer in the T-DM1 arms. Conclusion T-DM1 showed noninferior, but not superior, efficacy and better tolerability than did taxane plus trastuzumab for first-line treatment of HER2-positive, advanced breast cancer.
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Randomized Controlled Trial Comparative Study
Impact of Intensity-Modulated Radiation Therapy Technique for Locally Advanced Non-Small-Cell Lung Cancer: A Secondary Analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial.
Purpose Although intensity-modulated radiation therapy (IMRT) is increasingly used to treat locally advanced non-small-cell lung cancer (NSCLC), IMRT and three-dimensional conformal external beam radiation therapy (3D-CRT) have not been compared prospectively. This study compares 3D-CRT and IMRT outcomes for locally advanced NSCLC in a large prospective clinical trial. Patients and Methods A secondary analysis was performed to compare IMRT with 3D-CRT in NRG Oncology clinical trial RTOG 0617, in which patients received concurrent chemotherapy of carboplatin and paclitaxel with or without cetuximab, and 60- versus 74-Gy radiation doses. ⋯ IMRT also produced lower heart doses ( P < .05), and the volume of heart receiving 40 Gy (V40) was significantly associated with OS on adjusted analysis ( P < .05). The lung V5 was not associated with any ≥ grade 3 toxicity, whereas the lung V20 was associated with increased ≥ grade 3 pneumonitis risk on multivariable analysis ( P = .026). Conclusion IMRT was associated with lower rates of severe pneumonitis and cardiac doses in NRG Oncology clinical trial RTOG 0617, which supports routine use of IMRT for locally advanced NSCLC.