Journal of clinical oncology : official journal of the American Society of Clinical Oncology
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Randomized Controlled Trial Multicenter Study
Adjuvant Cyclophosphamide and Docetaxel With or Without Epirubicin for Early TOP2A-Normal Breast Cancer: DBCG 07-READ, an Open-Label, Phase III, Randomized Trial.
Purpose Administration of anthracycline and taxane therapy in the adjuvant setting is considered a standard for breast cancer. We evaluated a non-anthracycline-based regimen in TOP2A-normal patients. Patients and Methods In this multicenter, open-label, phase III trial, 2,012 women with early TOP2A-normal breast cancer and at least one high-risk factor were randomly assigned to receive six cycles of docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks (DC) or three cycles of epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) followed by three cycles of docetaxel (100 mg/m2; EC-D). ⋯ Patients with grade 3 tumors derived most benefit from DC, and patients with grade 1 to 2 tumors derived most benefit from EC-D (DFS: interaction P = .02; and OS: interaction P = .03). Patients receiving EC-D reported significantly more stomatitis, myalgia or arthralgia, vomiting, nausea, fatigue, and peripheral neuropathy, whereas edema was more frequent after DC. Conclusion This study provides evidence to support no overall outcome benefit from adjuvant anthracyclines in patients with early TOP2A-normal breast cancer.
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Randomized Controlled Trial Multicenter Study
Clinical Impact of the Cell-of-Origin Classification and the MYC/ BCL2 Dual Expresser Status in Diffuse Large B-Cell Lymphoma Treated Within Prospective Clinical Trials of the German High-Grade Non-Hodgkin's Lymphoma Study Group.
Purpose To explore the prognostic impact and interdependence of the cell-of-origin (COO) classification, dual expression (DE) of MYC and BCL2 proteins, and MYC, BCL2, and BCL6 translocations in two prospectively randomized clinical trials of patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods Overall, 452 formalin-fixed paraffin-embedded samples from two prospective, randomized DLBCL trials (RICOVER-60, prospective, randomized study for patients > 60 years, all IPI groups; and R-MegaCHOEP, prospective, randomized study for patients ≤ 60 years with age-adjusted IPI 2,3) of the German High-Grade Non-Hodgkin Lymphoma Study Group were analyzed with the Lymph2Cx assay for COO classification, with immunohistochemistry for MYC and BCL2, and with fluorescent in situ hybridization for MYC, BCL2, and BCL6 rearrangements. Results COO classification was successful in 414 of 452 samples. ⋯ When data from patients with nonDE were analyzed separately, the outcome of patients in the ABC subgroup was inferior to that of patients in the GCB subgroup (5-year PFS rate, 68% [95% CI, 52% to 85%] v 85% [95% CI, 74% to 96%]; P = .04). Conclusion COO profiling in two prospective randomized DLBCL trials failed to identify prognostic subgroups, whereas dual expression of MYC and BCL2 was predictive of poor survival. Evaluation of prognostic or predictive biomarkers in the management of DLBCL, such as the COO, within prospective clinical trials will be important in the future.
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Randomized Controlled Trial Multicenter Study
Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial.
Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refractory ALK-positive NSCLC. Patients and Methods Patients were stratified by brain metastases and best response to crizotinib. ⋯ A subset of pulmonary adverse events with early onset (median onset: day 2) occurred in 14 of 219 treated patients (all grades, 6%; grade ≥ 3, 3%); none occurred after escalation to 180 mg in arm B. Seven of 14 patients were successfully retreated with brigatinib. Conclusion Brigatinib yielded substantial whole-body and intracranial responses as well as robust progression-free survival; 180 mg (with lead-in) showed consistently better efficacy than 90 mg, with acceptable safety.
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Purpose The multicohort phase Ib KEYNOTE-028 (NCT02054806) study was designed to evaluate the safety and efficacy of pembrolizumab, an anti-programmed death 1 monoclonal antibody, in patients with programmed death ligand 1 (PD-L1) -positive advanced solid tumors. The results from the advanced endometrial cancer cohort are reported. Patients and Methods Female patients with locally advanced or metastatic PD-L1-positive endometrial cancer who had experienced progression after standard therapy were eligible. ⋯ Grade 3 treatment-related AEs were reported in four patients. No patient experienced a grade 4 AE, and no patient discontinued treatment because of an AE. Conclusion Pembrolizumab demonstrated a favorable safety profile and durable antitumor activity in a subgroup of patients with heavily pretreated advanced PD-L1-positive endometrial cancer.
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Purpose Patients' understanding of their illness is key for making informed treatment decisions, yet studies suggest an association between prognostic awareness and worse quality of life (QOL) and mood among patients with advanced cancer. We sought to explore the relationships among prognostic awareness, coping, QOL, and mood in patients with newly diagnosed, incurable cancer. Methods We assessed patients' self-reported health status and treatment goal (Prognosis and Treatment Perceptions Questionnaire), coping (Brief COPE), QOL (Functional Assessment of Cancer Therapy-General), and mood (Hospital Anxiety and Depression Scale) within 8 weeks of incurable lung or GI cancer diagnosis. ⋯ Specifically, subgroup analyses showed that greater use of positive reframing was related to better QOL (B = 2.61; P < .001) and less depression (B = -0.78; P < .001) among patients who reported a terminally ill health status. Active coping was associated with better QOL (B = 3.50; P < .001) and less depression (B = -1.01; P < .001) among patients who acknowledged their oncologist's treatment goal was not "to cure my cancer." Conclusion Prognostic awareness is related to worse QOL and mood in patients with newly diagnosed, incurable cancer; however, the use of certain coping strategies may buffer these relationships. Interventions to improve patients' prognostic awareness should seek to cultivate more adaptive coping strategies in order to enhance QOL and mood.