Purpose To provide guidance regarding the practical assessment and management of vulnerabilities in older patients undergoing chemotherapy. Methods An Expert Panel was convened to develop clinical practice guideline recommendations based on a systematic review of the medical literature. Results A total of 68 studies met eligibility criteria and form the evidentiary basis for the recommendations. Recommendations In patients ≥ 65 years receiving chemotherapy, geriatric assessment (GA) should be used to identify vulnerabilities that are not routinely captured in oncology assessments. Evidence supports, at a minimum, assessment of function, comorbidity, falls, depression, cognition, and nutrition. The Panel recommends instrumental activities of daily living to assess for function, a thorough history or validated tool to assess comorbidity, a single question for falls, the Geriatric Depression Scale to screen for depression, the Mini-Cog or the Blessed Orientation-Memory-Concentration test to screen for cognitive impairment, and an assessment of unintentional weight loss to evaluate nutrition. Either the CARG (Cancer and Aging Research Group) or CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) tools are recommended to obtain estimates of chemotherapy toxicity risk; the Geriatric-8 or Vulnerable Elders Survey-13 can help to predict mortality. Clinicians should use a validated tool listed at ePrognosis to estimate noncancer-based life expectancy ≥ 4 years. GA results should be applied to develop an integrated and individualized plan that informs cancer management and to identify nononcologic problems amenable to intervention. Collaborating with caregivers is essential to implementing GA-guided interventions. The Panel suggests that clinicians take into account GA results when recommending chemotherapy and that the information be provided to patients and caregivers to guide treatment decision making. Clinicians should implement targeted, GA-guided interventions to manage nononcologic problems. Additional information is available at www.asco.org/supportive-care-guidelines .

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Purpose Docetaxel and cyclophosphamide (TC) was superior to doxorubicin and cyclophosphamide (AC) in a trial in early breast cancer. However, activity of TC relative to AC regimens with a taxane (TaxAC) is unknown. Methods In a series of three adjuvant trials, women were randomly assigned to TC for six cycles (TC6) or to a standard TaxAC regimen. US Oncology Research (USOR) 06-090 compared TC6 with docetaxel, doxorubicin, and cyclophosphamide (TAC6). National Surgical Adjuvant Breast and Bowel Project (NSABP) B-46-I/USOR 07132 compared TC6, TAC6, or TC6 plus bevacizumab. NSABP B-49 compared TC6 with several standard AC and taxane combination regimens. Before any analysis of individual trials, a joint efficacy analysis of TC versus the TaxAC regimens was planned, with invasive disease-free survival (IDFS) as the primary end point. Patients who received TC6 plus bevacizumab on NSABP B-46-I/USOR 07132 were not included. A hazard ratio (HR) from a stratified Cox model that exceeded 1.18 for TC6 versus TaxAC was predefined as inferiority for TC6. The prespecified interim monitoring plan was to report for futility if the HR was > 1.18 when 334 IDFS events were observed (50% of 668 events required for definitive analysis). Results A total of 2,125 patients were randomly assigned to receive TC6 regimens and 2,117 patients were randomly assigned to receive TaxAC regimens. The median follow-up time was 3.3 years. There were 334 IDFS events, and the HR for TC6 versus TaxAC was 1.202 (95% CI, 0.97 to 1.49), which triggered early reporting for futility. The 4-year IDFS was 88.2% for TC6 and was 90.7% for TaxAC ( P = .04). Tests for treatment interaction by protocol, hormone receptor status, and nodal status were negative. Conclusion The TaxAC regimens improved IDFS in patients with high-risk human epidermal growth factor receptor 2-negative breast cancer compared with the TC6 regimen.

Background NSABP B-35 is a phase III trial comparing anastrozole (A) to tamoxifen (T) for breast cancer-free interval (BCFI), defined as time from randomization to any breast cancer event: local, regional, distant, or contralateral, invasive or DCIS. Methods Postmenopausal women with hormone-positive DCIS treated by lumpectomy with clear resection margins and whole breast irradiation were randomized to receive either 20mg/day T or 1mg/day A (blinded) for 5 years. Stratification was by <60 versus ≥60 years. Findings From 1/6/2003–6/15/2006, 3,104 patients were entered and randomized. As of 2/28/15, follow-up information was available on 3,083 patients for OS and 3,077 for all other disease-free endpoints, with median follow-up of 9 years. There were 212 BCFI events, 122 in the T group and 90 in the A group (HR, 0.73; 95% CI, 0.56–0.96; p=0.0234). 10-year estimates for BCFI were 89.1% (95% CI, 86.8–91.0) for T and 93.1% (95% CI, 91.5–94.5) for A. A significant time-by-treatment interaction (p=0.0410) became evident later in the study. There was a significant interaction between treatment and age group (p=0.0379); A is superior only in women <60 years. There were 495 DFS events: 260 in the T group, 235 in the A group (HR, 0.89; 95% CI, 0.75–1.07; p=0.21). 10-year DFS estimates were 77.9% (95% CI, 75.0–80.6) for T and 82.7% (95% CI, 80.4–84.7) for A. There were 186 deaths: 88 in the T group, 98 in the A group (HR, 1.11; 95% CI, 0.83–1.48; p=0.48). 10-year OS estimates were 92.1% (95% CI, 90.1–93.7) for T, 92.5% (95% CI, 90.8–93.9) for A. Eight deaths were due to breast cancer in the T group and five in the A. There were 69 cases of invasive breast cancer in the T group and 43 in the A group (HR, 0.62; 95% CI, 0.42–0.90; p=0.0123). A significant reduction in contralateral breast cancers with A (HR, 0.64; 95% CI, 0.43–0.96; p=0.0322) was identified. Interpretation Anastrozole provided a significant improvement compared to tamoxifen for BCFI, primarily in women <60 years. Funding US NCI; AstraZeneca Pharmaceuticals LP.