Auckland District Health Board (ADHB) is a district health board that provides healthcare in the Auckland Region in New Zealand, mainly on the Auckland isthmus. This district health board has existed since 2001 and is governed by a part-elected, part-appointed board.
BACKGROUND:Dual anti-human epidermal growth factor receptor 2 (HER2) therapy plus chemotherapy followed by maintenance treatment with HER2-targeted and endocrine therapies is standard first-line treatment for hormone-receptor-positive, HER2-positive metastatic breast cancer. On the basis of preclinical and clinical data, the addition of palbociclib (a selective inhibitor of cyclin-dependent kinases 4 and 6) may overcome resistance to both endocrine and HER2-directed therapies. METHODS:In this phase 3, open-label, randomized trial, we enrolled patients with hormone-receptor-positive, HER2-positive metastatic breast cancer who did not have disease progression after four to eight cycles of chemotherapy plus HER2-targeted therapy. Patients were randomly assigned in a 1:1 ratio to receive maintenance HER2-targeted and endocrine therapies with or without palbociclib. The primary end point was investigator-assessed progression-free survival. Secondary end points included the objective response, clinical benefit, safety, and overall survival. RESULTS:A total of 518 patients underwent randomization: 261 were assigned to receive palbociclib and 257 to receive standard therapy. At a median follow-up of 53.5 months, patients in the palbociclib group had significantly longer progression-free survival than those in the standard-therapy group (median duration, 44.3 months vs. 29.1 months; hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; two-sided P = 0.02). Grade 3 and 4 adverse events, predominantly from neutropenia, occurred in 79.7% and 10.0% of the patients, respectively, in the palbociclib group, as compared with 30.6% and 3.6% of the patients, respectively, in the standard-therapy group. CONCLUSIONS:The addition of palbociclib to maintenance anti-HER2 and endocrine therapies led to a significant improvement in progression-free survival over standard therapy, with increased toxic effects, mainly neutropenia. (Funded by Pfizer and others; PATINA ClinicalTrials.gov number, NCT02947685.).
Older men suffer from hip FFx (fragility fracture) at femoral neck T-score approximately 0.6 higher than older women, thus we proposed a new category of low BMD status, osteofrailia, for older Caucasian men with femoral neck T-score ≤ −2.0 (T-score ≤ −2.1 for older East Asian men) who have an increased risk of hip FFx. Around the age of 78 years, mean LS (lumbar spine) QCT BMD is around 68 mg/mL and 100 mg/mL for East Asian men and Caucasian men, respectively. For East Asian men, LS QCT BMD <68 mg/mL offers a sensitivity of 77
The anti-fracture efficacy of most osteoporosis drugs is assessed in trials of up to 3 yr duration. However, treatment of osteoporosis is required long-term, so it is important to know whether effectiveness of treatment changes over time. To date, this information has only been available from open extensions of the treatment groups from clinical trials. Such data are subject to selective loss of frailer patients from the cohort, and no placebo comparator group is available to permit reliable measurement of anti-fracture efficacy. The 6-yr Auckland zoledronate RCT administered zoledronate or placebo every 18 mo to 2000 osteopenic women aged >65 yr. It is longer than most osteoporosis trials, and only 3.6% of participants withdrew or were lost to follow-up. Therefore, anti-fracture efficacy can be validly compared between the first and second halves of this study. There were 178 non-vertebral fractures in the placebo group and 108 in the zoledronate group (excluding fractures of the hands, feet, and face). Fracture rates per 1000 women-years in the placebo group were 28 (95% CI 23, 35) and 32 (26, 40) in years 1-3 and years 4-6, respectively. In the zoledronate group, fracture rates were 23 (18, 30) and 13 (9, 18) per 1000 women-years in the first and second halves of the study. The rate ratios for non-vertebral fractures were 0.83 (0.60, 1.14) in years 1-3, and 0.40 (0.27, 0.58) in years 4-6 (between-period comparison, p < .05). Rate ratios for total fragility fractures, which include vertebral fractures also, showed a similar pattern: years 1-3, 0.76 (0.56, 1.02) and years 4-6, 0.39 (0.29, 0.53). These findings suggest that the efficacy for non-vertebral fracture prevention of anti-resorptive drugs has been underestimated because of the short-term evaluation of their effects. Further, it indicates that longer term treatment with these drugs may yield greater benefit to patients.
