Journal of clinical oncology : official journal of the American Society of Clinical Oncology
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Randomized Controlled Trial Multicenter Study
Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti-T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease-Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell Transplantation.
Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. ⋯ Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.
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Randomized Controlled Trial
Cost-Effectiveness Analysis of Monthly Zoledronic Acid, Zoledronic Acid Every 3 Months, and Monthly Denosumab in Women With Breast Cancer and Skeletal Metastases: CALGB 70604 (Alliance).
Purpose Skeletal-related events (SREs) such as pathologic fracture, spinal cord compression, or the necessity for radiation or surgery to bone metastasis cause considerable morbidity, decrements in quality of life, and costs to the health care system. The results of a recent large randomized trial (Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology [CALGB/Alliance 70604]) showed that zoledronic acid (ZA) every 3 months was noninferior to monthly ZA in reducing the risks of SREs. We sought to determine the cost-effectiveness (CE) of monthly ZA, ZA every 3 months, and monthly denosumab in women with breast cancer and skeletal metastases. ⋯ Conclusion ZA every 3 months was more CE in reducing the risks of SRE than monthly denosumab. This analysis was one of the first to incorporate the costs of generic ZA and one of the first independent CE analyses not sponsored by either Novartis or Amgen, the makers of ZA and denosumab, respectively. ZA every 3 months is the more CE option and more reasonable alternative to monthly denosumab.
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Randomized Controlled Trial Multicenter Study
Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057).
Purpose Nivolumab, a programmed death-1 inhibitor, prolonged overall survival compared with docetaxel in two independent phase III studies in previously treated patients with advanced squamous (CheckMate 017; ClinicalTrials.gov identifier: NCT01642004) or nonsquamous (CheckMate 057; ClinicalTrials.gov identifier: NCT01673867) non-small-cell lung cancer (NSCLC). We report updated results, including a pooled analysis of the two studies. Methods Patients with stage IIIB/IV squamous (N = 272) or nonsquamous (N = 582) NSCLC and disease progression during or after prior platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks). ⋯ No patient in either docetaxel group had an ongoing response. In the pooled analysis, the relative reduction in the risk of death with nivolumab versus docetaxel was 28% (hazard ratio, 0.72; 95% CI, 0.62 to 0.84), and rates of treatment-related adverse events were lower with nivolumab than with docetaxel (any grade, 68% v 88%; grade 3 to 4, 10% v 55%). Conclusion Nivolumab provides long-term clinical benefit and a favorable tolerability profile compared with docetaxel in previously treated patients with advanced NSCLC.
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Randomized Controlled Trial Multicenter Study
Long-Term Follow-Up of Cardiac Function and Quality of Life for Patients in NSABP Protocol B-31/NRG Oncology: A Randomized Trial Comparing the Safety and Efficacy of Doxorubicin and Cyclophosphamide (AC) Followed by Paclitaxel With AC Followed by Paclitaxel and Trastuzumab in Patients With Node-Positive Breast Cancer With Tumors Overexpressing Human Epidermal Growth Factor Receptor 2.
Purpose Early cardiac toxicity is a risk associated with adjuvant chemotherapy plus trastuzumab. However, objective measures of cardiac function and health-related quality of life are lacking in long-term follow-up of patients who remain cancer free after completion of adjuvant treatment. Patients and Methods Patients in NSABP Protocol B-31 received anthracycline and taxane chemotherapy with or without trastuzumab for adjuvant treatment of node-positive, human epidermal growth factor receptor 2-positive early-stage breast cancer. ⋯ Lower DASI scores correlated with age and use of medications for hypertension, cardiac conditions, diabetes, and hyperlipidemia, but not with whether patients had received trastuzumab. Conclusion In patients without underlying cardiac disease at baseline, the addition of trastuzumab to adjuvant anthracycline and taxane-based chemotherapy does not result in long-term worsening of cardiac function, cardiac symptoms, or health-related quality of life. The DASI questionnaire may provide a simple and useful tool for monitoring patient-reported changes that reflect cardiac function.
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Randomized Controlled Trial Multicenter Study
Randomized Phase III and Extension Studies of Naldemedine in Patients With Opioid-Induced Constipation and Cancer.
Purpose Opioid-induced constipation (OIC) is a frequent and debilitating adverse effect (AE) of opioids-common analgesics for cancer pain. We investigated the efficacy and safety of a peripherally acting μ-opioid receptor antagonist, naldemedine (S-297995), for OIC, specifically in patients with cancer. Patients and Methods This phase III trial consisted of a 2-week, randomized, double-blind, placebo-controlled study (COMPOSE-4) and an open-label, 12-week extension study (COMPOSE-5). ⋯ Diarrhea was the most frequently reported TEAE in COMPOSE-4 (19.6% [19 of 97 patients] v 7.3% [seven of 96 patients] with naldemedine v placebo) and COMPOSE-5 (18.3% [24 of 131 patients] with naldemedine). Naldemedine was not associated with signs or symptoms of opioid withdrawal and had no notable impact on opioid-mediated analgesia. Conclusion Once-daily oral naldemedine 0.2 mg effectively treated OIC and was generally well tolerated in patients with OIC and cancer.