MARIANNE: Impact on Current Treatment of Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Implications for the Future.
J Clin Oncol. 2016 Nov 14;:JCO2016702712
Authors: Jhaveri K
PMID: 27918726 [PubMed - as supplied by publisher]
Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline.
J Clin Oncol. 2016 Dec 05;:JCO2016705400
Authors: Armenian SH, Lacchetti C, Barac A, Carver J, Constine LS, Denduluri N, Dent S, Douglas PS, Durand JB, Ewer M, Fabian C, Hudson M, Jessup M, Jones LW, Ky B, Mayer EL, Moslehi J, Oeffinger K, Ray K, Ruddy K, Lenihan D
Purpose Cardiac dysfunction is a serious adverse effect of certain cancer-directed therapies that can interfere with the efficacy of treatment, decrease quality of life, or impact the actual survival of the patient with cancer. The purpose of this effort was to develop recommendations for prevention and monitoring of cardiac dysfunction in survivors of adult-onset cancers. Methods Recommendations were developed by an expert panel with multidisciplinary representation using a systematic review (1996 to 2016) of meta-analyses, randomized clinical trials, observational studies, and clinical experience. Study quality was assessed using established methods, per study design. The guideline recommendations were crafted in part using the Guidelines Into Decision Support methodology. Results A total of 104 studies met eligibility criteria and compose the evidentiary basis for the recommendations. The strength of the recommendations in these guidelines is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms. Recommendations It is important for health care providers to initiate the discussion regarding the potential for cardiac dysfunction in individuals in whom the risk is sufficiently high before beginning therapy. Certain higher risk populations of survivors of cancer may benefit from prevention and screening strategies implemented during cancer-directed therapies. Clinical suspicion for cardiac disease should be high and threshold for cardiac evaluation should be low in any survivor who has received potentially cardiotoxic therapy. For certain higher risk survivors of cancer, routine surveillance with cardiac imaging may be warranted after completion of cancer-directed therapy, so that appropriate interventions can be initiated to halt or even reverse the progression of cardiac dysfunction.
PMID: 27918725 [PubMed - as supplied by publisher]
Telotristat Ethyl, a Tryptophan Hydroxylase Inhibitor for the Treatment of Carcinoid Syndrome.
J Clin Oncol. 2016 Oct 28;:JCO2016692780
Authors: Kulke MH, Hörsch D, Caplin ME, Anthony LB, Bergsland E, Öberg K, Welin S, Warner RR, Lombard-Bohas C, Kunz PL, Grande E, Valle JW, Fleming D, Lapuerta P, Banks P, Jackson S, Zambrowicz B, Sands AT, Pavel M
Purpose Preliminary studies suggested that telotristat ethyl, a tryptophan hydroxylase inhibitor, reduces bowel movement (BM) frequency in patients with carcinoid syndrome. This placebo-controlled phase III study evaluated telotristat ethyl in this setting. Patients and Methods Patients (N = 135) experiencing four or more BMs per day despite stable-dose somatostatin analog therapy received (1:1:1) placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg three times per day orally during a 12-week double-blind treatment period. The primary end point was change from baseline in BM frequency. In an open-label extension, 115 patients subsequently received telotristat ethyl 500 mg. Results Estimated differences in BM frequency per day versus placebo averaged over 12 weeks were -0.81 for telotristat ethyl 250 mg ( P < .001) and ‒0.69 for telotristat ethyl 500 mg ( P < .001). At week 12, mean BM frequency reductions per day for placebo, telotristat ethyl 250 mg, and telotristat ethyl 500 mg were -0.9, -1.7, and -2.1 , respectively. Responses, predefined as a BM frequency reduction ≥ 30% from baseline for ≥ 50% of the double-blind treatment period, were observed in 20%, 44%, and 42% of patients given placebo, telotristat ethyl 250 mg, and telotristat ethyl 500 mg, respectively. Both telotristat ethyl dosages significantly reduced mean urinary 5-hydroxyindole acetic acid versus placebo at week 12 ( P < .001). Mild nausea and asymptomatic increases in gamma-glutamyl transferase were observed in some patients receiving telotristat ethyl. Follow-up of patients during the open-label extension revealed no new safety signals and suggested sustained BM responses to treatment. Conclusion Among patients with carcinoid syndrome not adequately controlled by somatostatin analogs, treatment with telotristat ethyl was generally safe and well tolerated and resulted in significant reductions in BM frequency and urinary 5-hydroxyindole acetic acid.
PMID: 27918724 [PubMed - as supplied by publisher]
Reply to A. Ota et al, Y.H. Kim, and N. Van Der Steen et al.
J Clin Oncol. 2016 Dec 05;:JCO2016706978
Authors: Yang JC, Puri T, Orlando M, Cheng Y
PMID: 27918723 [PubMed - as supplied by publisher]
Multiple-Treatments Meta-Analysis: Are the Conclusions Supported by the Data?
J Clin Oncol. 2016 Dec 05;:JCO2016704775
Authors: Kraemer HC
PMID: 27918722 [PubMed - as supplied by publisher]
Unconvincing Benefit of Combination Therapy With Gefitinib and Pemetrexed in Advanced Non-Small-Cell Lung Cancer.
J Clin Oncol. 2016 Dec 05;:JCO2016704148
Authors: Ota A, Gyawali B, Matsuoka A, Ando Y
PMID: 27918721 [PubMed - as supplied by publisher]
What Is the Best Treatment of Locally Advanced Nasopharyngeal Carcinoma? An Individual Patient Data Network Meta-Analysis.
J Clin Oncol. 2016 Dec 05;:JCO2016674119
Authors: Ribassin-Majed L, Marguet S, Lee AW, Ng WT, Ma J, Chan AT, Huang PY, Zhu G, Chua DT, Chen Y, Mai HQ, Kwong DL, Cheah SL, Moon J, Tung Y, Chi KH, Fountzilas G, Bourhis J, Pignon JP, Blanchard P
Purpose The role of adjuvant chemotherapy (AC) or induction chemotherapy (IC) in the treatment of locally advanced nasopharyngeal carcinoma is controversial. The individual patient data from the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma database were used to compare all available treatments. Methods All randomized trials of radiotherapy (RT) with or without chemotherapy in nonmetastatic nasopharyngeal carcinoma were considered. Overall, 20 trials and 5,144 patients were included. Treatments were grouped into seven categories: RT alone (RT), IC followed by RT (IC-RT), RT followed by AC (RT-AC), IC followed by RT followed by AC (IC-RT-AC), concomitant chemoradiotherapy (CRT), IC followed by CRT (IC-CRT), and CRT followed by AC (CRT-AC). P-score was used to rank the treatments. Fixed- and random-effects frequentist network meta-analysis models were applied. Results The three treatments with the highest probability of benefit on overall survival (OS) were CRT-AC, followed by CRT and IC-CRT, with respective hazard ratios (HRs [95% CIs]) compared with RT alone of 0.65 (0.56 to 0.75), 0.77 (0.64 to 0.92), and 0.81 (0.63 to 1.04). HRs (95% CIs) of CRT-AC compared with CRT for OS, progression-free survival (PFS), locoregional control, and distant control (DC) were, respectively, 0.85 (0.68 to 1.05), 0.81 (0.66 to 0.98), 0.70 (0.48 to 1.02), and 0.87 (0.61 to 1.25). IC-CRT ranked second for PFS and the best for DC. CRT never ranked first. HRs of CRT compared with IC-CRT for OS, PFS, locoregional control, and DC were, respectively, 0.95 (0.72 to 1.25), 1.13 (0.88 to 1.46), 1.05 (0.70 to 1.59), and 1.55 (0.94 to 2.56). Regimens with more chemotherapy were associated with increased risk of acute toxicity. Conclusion The addition of AC to CRT achieved the highest survival benefit and consistent improvement for all end points. The addition of IC to CRT achieved the highest effect on DC.
PMID: 27918720 [PubMed - as supplied by publisher]
Nanoliposomal Irinotecan in the Clinical Practice Guideline for Metastatic Pancreatic Cancer: Applicability to Clinical Situations.
J Clin Oncol. 2016 Dec 05;:JCO2016701607
Authors: Wang-Gillam A, Von Hoff D, Siveke J, Hubner R, Belanger B, Pipas JM, Chen LT
PMID: 27918719 [PubMed - as supplied by publisher]
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 O(6)-Methylguanine-DNA Methyltransferase Biomarker Analyses.
J Clin Oncol. 2016 Dec 05;:JCO2015647685
Authors: Cloughesy T, Finocchiaro G, Belda-Iniesta C, Recht L, Brandes AA, Pineda E, Mikkelsen T, Chinot OL, Balana C, Macdonald DR, Westphal M, Hopkins K, Weller M, Bais C, Sandmann T, Bruey JM, Koeppen H, Liu B, Verret W, Phan SC, Shames DS
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. Methods At first recurrence after chemoradiation, bevacizumab-naïve patients with glioblastoma were randomly assigned 1:1 to receive Ona (15 mg/kg, once every 3 weeks) + Bev (15 mg/kg, once every 3 weeks) or Pla + Bev until disease progression. The primary end point was progression-free survival by response assessment in neuro-oncology criteria. Secondary end points were overall survival, objective response rate, duration of response, and safety. Exploratory biomarker analyses correlated efficacy with expression levels of MET ligand hepatocyte growth factor, O(6)-methylguanine-DNA methyltransferase promoter methylation, and glioblastoma subtype. Results Among 129 patients enrolled (Ona + Bev, n = 64; Pla + Bev, n = 65), baseline characteristics were balanced. The median progression-free survival was 3.9 months for Ona + Bev versus 2.9 months for Pla + Bev (hazard ratio, 1.06; 95% CI, 0.72 to 1.56; P = .7444). The median overall survival was 8.8 months for Ona + Bev and 12.6 months for Pla + Bev (hazard ratio, 1.45; 95% CI, 0.88 to 2.37; P = .1389). 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 O(6)-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.
PMID: 27918718 [PubMed - as supplied by publisher]
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Chemotherapy: A Glimmer of Hope?
J Clin Oncol. 2016 Dec 05;:JCO2016701987
Authors: Van Der Steen N, Rolfo CD, Pauwels P, Peters GJ, Giovannetti E
PMID: 27918717 [PubMed - as supplied by publisher]
Genome-Driven Paradigm for the Development of Selective Fibroblast Growth Factor Receptor Inhibitors.
J Clin Oncol. 2016 Dec 05;:JCO2016705061
Authors: Schram AM, Voss MH, Hyman DM
PMID: 27918716 [PubMed - as supplied by publisher]
What Mommy Does.
J Clin Oncol. 2016 Dec 05;:JCO2016698738
Authors: Mark M
PMID: 27918715 [PubMed - as supplied by publisher]
Reply to A. Wang-Gillam et al.
J Clin Oncol. 2016 Dec 05;:JCO2016707463
Authors: Sohal DP, Mangu PB, Laheru D, Khorana AA
PMID: 27918714 [PubMed - as supplied by publisher]
Gefitinib Plus Pemetrexed As First-Line Treatment in Patients With Nonsquamous Non-Small-Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations.
J Clin Oncol. 2016 Dec 05;:JCO2016702472
Authors: Kim YH
PMID: 27918713 [PubMed - as supplied by publisher]
Cost-Utility of Stepped Care Targeting Psychological Distress in Patients With Head and Neck or Lung Cancer.
J Clin Oncol. 2016 Dec 05;:JCO2016688739
Authors: Jansen F, Krebber AM, Coupé VM, Cuijpers P, de Bree R, Becker-Commissaris A, Smit EF, van Straten A, Eeckhout GM, Beekman AT, Leemans CR, Verdonck-de Leeuw IM
Purpose A stepped care (SC) program in which an effective yet least resource-intensive treatment is delivered to patients first and followed, when necessary, by more resource-intensive treatments was found to be effective in improving distress levels of patients with head and neck cancer or lung cancer. Information on the value of this program for its cost is now called for. Therefore, this study aimed to assess the cost-utility of the SC program compared with care-as-usual (CAU) in patients with head and neck cancer or lung cancer who have psychological distress. Patients and Methods In total, 156 patients were randomly assigned to SC or CAU. Intervention costs, direct medical costs, direct nonmedical costs, productivity losses, and health-related quality-of-life data during the intervention or control period and 12 months of follow-up were calculated by using Trimbos and Institute of Medical Technology Assessment Cost Questionnaire for Psychiatry, Productivity and Disease Questionnaire, and EuroQol-5 Dimension measures and data from the hospital information system. The SC program's value for the cost was investigated by comparing mean cumulative costs and quality-adjusted life years (QALYs). Results After imputation of missing data, mean cumulative costs were -€3,950 (95% CI, -€8,158 to -€190) lower, and mean number of QALYs was 0.116 (95% CI, 0.005 to 0.227) higher in the intervention group compared with the control group. The intervention group had a probability of 96% that cumulative QALYs were higher and cumulative costs were lower than in the control group. Four additional analyses were conducted to assess the robustness of this finding, and they found that the intervention group had a probability of 84% to 98% that cumulative QALYs were higher and a probability of 91% to 99% that costs were lower than in the control group. Conclusion SC is highly likely to be cost-effective; the number of QALYs was higher and cumulative costs were lower for SC compared with CAU.
PMID: 27918712 [PubMed - as supplied by publisher]