Prospective cost-effectiveness analysis of genomic profiling in breast cancer

BackgroundThe cost-effectiveness of the 70-gene signature (70-GS) (MammaPrint®) has earlier been estimated using retrospective validation data. Based on the prospective 5-year survival data of the microarRAy-prognoSTics-in-breast-cancER (RASTER) study, the aim here was to evaluate the cost-effectiveness reflecting the actual use in clinical practice, including reality-based compliance rates.MethodsCosts and outcomes (quality-adjusted-life-years (QALYs)) were calculated in node-negative (N?) patients included in the RASTER study (n = 427). Sensitivity and specificity of the 70-gene and Adjuvant! Online (AO) were based on 5-year distant-disease-free survival (DDFS). Subgroup analyses were performed for two groups for whom benefit of the 70-gene had earlier been reported: (1) ductal, oestrogen receptor-positive (ER+), tumour diameter 10–30 mm, grade II, age 40–70; (2) ductal, oestrogen receptor-positive, tumour diameter 5–30 mm, grade II/III and age 40–70.ResultsBased on 5-year survival data, the cost-effectiveness of the 70-gene signature versus AO was prospectively confirmed. The total health care costs per patient were €26,786 for the 70-gene and €29,187 for AO. The quality adjusted life years yielded 12.49 and 11.88, respectively. The subgroups retrieved slightly higher life gains and higher costs, but all resulted finally in a favourable position for the 70-gene signature.ConclusionsThe use of the 70-gene signature, as judged appropriate by doctors and patients and supported by a low risk 70-gene signature as an oncological safe choice, was also found to be cost-effective.     

Outcome of BRCA1- compared with BRCA2-associated ovarian cancer: a nationwide study in the Netherlands

BackgroundRecent studies suggested an improved overall survival (OS) for BRCA2- versus BRCA1-associated epithelial ovarian cancer (EOC), whereas the impact of chemotherapy is not yet clear. In a nationwide cohort, we examined the results of primary treatment, progression-free survival (PFS), treatment-free interval (TFI), and OS of BRCA1 versus BRCA2 EOC patients.MethodsTwo hundred and forty-five BRCA1- and 99 BRCA2-associated EOC patients were identified through all Dutch university hospitals. Analyses were carried out with the Pearson's Chi-square test, Kaplan–Meier, and Cox regression methods.ResultsBRCA1 patients were younger at EOC diagnosis than BRCA2 patients (51 versus 55 years; P < 0.001), without differences regarding histology, tumor grade, and International Federation of Gynecology and Obstetrics (FIGO) stage. Complete response rates after primary treatment, including chemotherapy, did not differ between BRCA1 (86%) and BRCA2 patients (90%). BRCA1 versus BRCA2 patients had a shorter PFS (median 2.2 versus 3.9 years, respectively; P = 0.006), TFI (median 1.7 versus 2.8 years; P = 0.009), and OS (median 6.0 versus 9.7 years; P = 0.04). Differences could not be explained by age at diagnosis, FIGO stage or type of treatment.ConclusionsPFS and OS were substantially longer in BRCA2- than in BRCA1-associated EOC patients. While response rates after primary treatment were similarly high in both groups, TFI, as surrogate for chemosensitivity, was significantly longer in BRCA2 patients.     

Does training general practitioners result in more shared decision making during consultations?

ObjectiveWe conducted a clustered randomised controlled trial to study the effects of shared decision making (SDM) on patient recovery. This study aims to determine whether GPs trained in SDM and reinforcing patients’ treatment expectations showed more trained behaviour during their consultations than untrained GPs.MethodsWe compared 86 consultations conducted by 23 trained GPs with 89 consultations completed by 19 untrained GPs. The primary outcomes were SDM, as measured by the OPTION scale, and positive reinforcement, as measured by global observation. Secondary outcomes were the level of autonomy in decision making and the duration of the consultation.ResultsIntervention consultations scored significantly higher on most elements of the OPTION scale, and on the autonomy scale; however, they were three minutes longer in duration, and the mean OPTION score of the intervention group remained below average.ConclusionTraining GPs resulted in more SDM behaviour and more autonomy for the patient; however, this increase is not attributable to the adoption of a patient perspective. Furthermore, while we aimed to demonstrate that SDM facilitates the reinforcement of patients’ positive expectations, the measurement of this behaviour was not reliable.Practice implicationsIn supporting SDM, professionals should give greater attention to patients’ treatment expectations.     

ASO Author Reflections: Impact of Preoperative MRI on Patients With Screen-Detected Invasive Breast Cancer Undergoing Breast-Conserving Surgery

Annals of Surgical Oncology -     

Role of Clinical Pharmacology in the Development of Antiplatelet Drugs

PurposeThis review discusses the role of clinical pharmacology in the development of low-dose aspirin and other antiplatelet agents during the past 30 years, emphasizing the main determinants of several success stories as well as of complete failures in the field.MethodsThe author employs personal appraisal of the literature, with emphasis on personal contributions to the field.FindingsLow-dose aspirin provides an interesting paradigm of the independent development of a “new” antiplatelet agent by the medical/scientific community. Aspirin “resistance,” improved dosing regimens for personalized therapy, and chemoprevention of colorectal cancer are thoroughly discussed. The industry-driven development paradigm includes 12 mechanism-based antiplatelet agents. Of those completing Phase 3, only 6 have been approved for the acute treatment or secondary prevention of atherothrombosis. Inadequate Phase 2 studies were largely involved in Phase 3 failures.ImplicationsThe design of mechanism-based pharmacodynamic biomarkers and sophisticated Phase 2 investigations appear as an important key to successful drug development in this field. Clinical pharmacology has an excellent track record in this endeavor, and its role needs to be expanded, as suggested by the case studies discussed in this review. Finally, the choice of appropriate platelet-dependent end points and homogeneous clinical settings for Phase 3 trials not only represent desirable objectives for an integrated scientific and regulatory discussion but also deserve proper ethical consideration by all stakeholders to avoid an unacceptable burden of drug toxicity and an unsustainable waste of financial resources.