Purpose Abiraterone acetate (AA) is a standard of care for metastatic castration-resistant prostate cancer (CRPC). Despite a large food effect, AA was administered under fasting conditions in its pivotal trials. We sought to test the hypothesis that low-dose AA (LOW; 250 mg with a low-fat meal) would have comparable activity to standard AA (STD; 1,000 mg fasting) in patients with CRPC. Patients and Methods Patients (n = 72) with progressive CRPC from seven institutions in the United States and Singapore were randomly assigned to STD or LOW. Both arms received prednisone 5 mg twice daily. Prostate-specific antigen (PSA) was assessed monthly, and testosterone/dehydroepiandrosterone sulfate were assessed every 12 weeks with disease burden radiographic assessments. Plasma was collected for drug concentrations. Log change in PSA, as a pharmacodynamic biomarker for efficacy, was the primary end point, using a noninferiority design. Progression-free survival (PFS), PSA response (≥ 50% reduction), change in androgen levels, and pharmacokinetics were secondary end points. Results Thirty-six patients were accrued to both arms. At 12 weeks, there was a greater effect on PSA in the LOW arm (mean log change, -1.59) compared with STD (-1.19), and noninferiority of LOW was established according to predefined criteria. The PSA response rate was 58% in LOW and 50% in STD, and the median PFS was approximately 9 months in both groups. Androgen levels decreased similarly in both arms. Although there was no difference in PSA response or PFS, abiraterone concentrations were higher in STD. Conclusion Low-dose AA (with low-fat breakfast) is noninferior to standard dosing with respect to PSA metrics. Given the pharmacoeconomic implications, these data warrant consideration by prescribers, payers, and patients. Additional studies are indicated to assess the long-term efficacy of this approach.
We identified racial disparities in omission of ODX testing but no differences in chemotherapy receipt if ODX test results were obtained, suggesting increasing access to ODX testing may improve racial equality in efficacious use of adjuvant chemotherapy for ER-positive HER2-negative breast cancer.
Background
The Oncotype DX recurrence score (RS) is used as a tool for making decisions about chemotherapy for patients who have hormone receptor (estrogen receptor or progesterone receptor)‐positive, HER2‐negative breast cancer. There is no benefit from chemotherapy among patients aged ≥50 years who have lymph node‐negative disease and an RS from 11 to 25, but the benefit of chemotherapy in the lymph node‐positive group remains unknown.
Methods
On the basis of data from the National Cancer Data Base between 2010 and 2014, a nationwide, retrospective cohort study included 73,185 women who had stage I through IIIA breast cancer and an RS between 11 and 30.
Results
Receipt of chemotherapy was associated with a reduced risk of death among patients who had lymph node‐positive breast cancer (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.45‐0.74; P < .001) after adjusting for other prognostic factors in a multivariable Cox model. The 5‐year survival gain ranged from 1.3% (RS 11‐17 subgroup), to 3.3% (RS 18‐25 subgroup), and to 6.7% (RS 26‐30 subgroup). Among patients who had lymph node‐negative disease, chemotherapy was associated with a reduced risk of death for those with an RS from 25 to 30 (HR, 0.68; 95% CI, 0.48‐0.96; P = .03; 5‐year survival gain, 1.8%), but there was no benefit from chemotherapy for patients who had an RS from 11 to 17 (HR, 0.97; 95% CI, 0.61‐1.55; P = .90), and there was a marginally significant benefit for women who had an RS from 18 to 25 (HR, 0.79; 95% CI, 0.62‐1.00; P = .05). Similar results were observed using propensity score‐matching method.
Conclusions
The benefit of chemotherapy for patients with breast cancer who have an intermediate RS is driven in a nonlinear fashion by RS: the higher the RS, the larger the absolute benefit. Findings from this study underscore the utility of real‐world data to inform joint decision making in practice.
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