Preservation of quality of life in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer treated with tucatinib or placebo when added to trastuzumab and capecitabine (HER2CLIMB trial).

AIMS: In HER2CLIMB, tucatinib significantly improved progression-free and overall survival in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer. We evaluated the impact of tucatinib on health-related quality of life (HR-QoL) in HER2CLIMB. METHODS: Patients were randomised 2:1 to tucatinib or placebo combined with trastuzumab and capecitabine. Starting with protocol version 7, the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) questionnaire and EQ visual analogue scale (VAS) were administered at day 1 of cycle 1, every two cycles during cycles 3-9, every three cycles during cycle 12 and thereafter and at each patient's 30-day follow-up visit. RESULTS: Among 364 patients eligible for HR-QoL assessment, 331 (91%) completed ≥1 assessment. EQ-VAS scores were similar for both arms at baseline and maintained throughout treatment. EQ-5D-5L scores were similar between the treatment arms, stable throughout therapy and worsened after discontinuing treatment. Risk of meaningful deterioration (≥7 points) on EQ-VAS was reduced 19% in the tucatinib vs. placebo arm (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.55, 1.18); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.8 months (4.3, -) in the placebo arm. Among patients with brain metastases (n = 164), risk of meaningful deterioration on EQ-VAS was reduced 49% in the tucatinib arm (HR: 0.51; 95% CI: 0.28, 0.93); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.5 months (4.2, -) in the placebo arm. CONCLUSIONS: HR-QoL was preserved for patients with HER2+ metastatic breast cancer who were treated with tucatinib added to trastuzumab and capecitabine and maintained longer with tucatinib therapy than without it among those with brain metastases. CLINICAL TRIAL REGISTRATION: NCT02614794.

Does the introduction of sentinel node biopsy increase the number of node positive patients with early breast cancer? A population based study form the Danish Breast Cancer Cooperative Group.

BACKGROUND: The validation series of sentinel lymph node biopsy (SLNB) in the treatment of breast cancer have shown that 10-20% more lymph node metastases are detected. However, their impact has never been studied in populations where the method has been fully implemented. In a population-based setting, the objective of the current study was to estimate the increased risk of metastases after introduction of the sentinel lymph node biopsy technique. METHODS: We identified all new breast cancer patients in three different counties in two time periods (1996-1997 and 2002-2003). The study cohort was comprised of 2 932 patients. The main outcome was the frequency of patients with metastases. The frequencies of patients with metastases were compared as well as adjusted (using a multivariate logistic regression) and unadjusted odds-ratio for detecting lymph node metastases. RESULTS: In counties where sentinel lymph node biopsy was implemented, the frequency of patients with lymph node metastases increased significantly 7.3% (95% CI: 1.0-13.7%) and 13.3% (95% CI: 7.3-19.3%), respectively. In the county without sentinel lymph node biopsy, an insignificant increase of 6.9% (-0.1-13.9%) in the frequency of patients with metastases was seen. The adjusted odds- ratio for detecting lymph node metastases was 1.41 (1.07-1.87) and 1.70 (1.30-2.23) in the counties with SLNB. CONCLUSION: The frequency of patients with metastases increased significantly in counties where sentinel lymph node biopsy was implemented.

Phase III trial comparing three doses of docetaxel for second-line treatment of advanced breast cancer.

PURPOSE: To evaluate whether a relationship exists between docetaxel dose and clinical response in the treatment of patients with advanced breast cancer. PATIENTS AND METHODS: Patients whose cancer had progressed after one prior chemotherapy regimen for advanced breast cancer or had recurred during or within 6 months of adjuvant chemotherapy were randomly assigned to docetaxel 60, 75, or 100 mg/m2 intravenously every 3 weeks. RESULTS: Five hundred twenty-seven patients were randomly assigned (intent to treat [ITT]), and 524 were assessable for toxicity. In the population assessable for efficacy (n = 407), logistic regression analysis showed that increasing docetaxel dose was significantly associated with higher response rate (P = .007) and improved time to progression (TTP; P = .014). In the ITT analysis, a significant dose-response relationship was observed for tumor response (P = .026) but not for TTP (P = .067). The incidences of most hematologic and nonhematologic toxicities were related to increasing dose, with grade 3 to 4 neutropenia occurring in 76.4%, 83.7%, and 93.4% and febrile neutropenia occurring in 4.7%, 7.4%, and 14.1% of patients administered the 60, 75, and 100 mg/m2 doses, respectively. One death was considered treatment related. CONCLUSION: A relationship between increasing dose of docetaxel and increased tumor response was observed across the dose range of 60 to 100 mg/m2 every 3 weeks. Toxicities were related to increasing dose. Depending on the therapy goal, any of the doses studied may be appropriate for second-line treatment of advanced breast cancer.