Trastuzumab deruxtecan versus trastuzumab emtansine in Asian patients with HER2-positive metastatic breast cancer.

The global phase 3 DESTINY-Breast03 study (ClinicalTrials.gov; NCT03529110) showed statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) with trastuzumab deruxtecan (T-DXd) over trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. Here, we report a subgroup analysis of Asian patients enrolled in DESTINY-Breast03. In total, 309 patients (149 in the T-DXd arm and 160 in the T-DM1 arm) from Asian countries and regions were randomized. At data cutoff (July 25, 2022), the median duration of follow-up in the Asian subpopulation was 29.0 months with T-DXd and 26.0 months with T-DM1. The PFS (determined by blinded independent central review) hazard ratio was 0.30 (95% confidence interval 0.22-0.41) favoring T-DXd over T-DM1 (median PFS 25.1 vs. 5.4 months). Median OS was not reached in the T-DXd arm and was 37.7 months in the T-DM1 arm. The median treatment duration was 15.4 months with T-DXd and 5.5 months with T-DM1. The incidence of grade ≥3 drug-related treatment-emergent adverse events was similar between both treatment arms (49.0% vs. 46.5%) and was consistent with the overall DESTINY-Breast03 population. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 12.9% of patients treated with T-DXd and 2.5% treated with T-DM1, with a higher incidence in Japanese patients; none of these were grade ≥4 events. These efficacy and safety data reinforce the favorable benefit-risk profile of T-DXd in HER2-positive mBC, including in the Asian subgroup.

Improving malignant fungating wound management among oncology nurses: a best practice implementation project.

INTRODUCTION: Appropriate malignant fungating wound (MFW) care is challenging for oncology nurses, leading to increased stress, compromised care quality, and poor patient outcomes. OBJECTIVE: This study aimed to address best practice barriers and develop evidence-based guidelines for MFW care. METHODS: This project was guided by the JBI Evidence Implementation Framework, which follows a seven-phase process. Both nurses' skills and patient charts were audited to determine compliance with best practices for comprehensive MFW assessment, wound photo records, use of validated wound assessment tools, appropriate wound care, and patient pain and satisfaction. Bandura's social learning theory was used to guide the development of an online education program and an objective structured clinical examination for skill improvement to prompt behavior change in nurses. A follow-up audit was conducted to measure improvements in knowledge, skills, and self-efficacy among nurses to validate the effectiveness of the intervention. RESULTS: The project resulted in improvements in all four evidence-based practice criteria: (1) comprehensive MFW assessments increased from 27% to 98%; (2) the inclusion of wound photos in medical records increased from 50% to 100%; (3) use of a validated wound assessment tool increased from 0% to 100%; and (4) appropriate interventions to manage wounds and maintain patients' quality of life increased from 50% to 90%. CONCLUSIONS: The project integrated a flexible education program, multidisciplinary collaboration, and leadership support to empower nurses to effectively manage MFWs. In addition, Bandura's social learning theory was used to influence nurses' behavior and bring about sustainable changes to organizational culture and practices. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A205.

Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer.

BACKGROUND: Trastuzumab emtansine is the current standard treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer whose disease progresses after treatment with a combination of anti-HER2 antibodies and a taxane. METHODS: We conducted a phase 3, multicenter, open-label, randomized trial to compare the efficacy and safety of trastuzumab deruxtecan (a HER2 antibody-drug conjugate) with those of trastuzumab emtansine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. The primary end point was progression-free survival (as determined by blinded independent central review); secondary end points included overall survival, objective response, and safety. RESULTS: Among 524 randomly assigned patients, the percentage of those who were alive without disease progression at 12 months was 75.8% (95% confidence interval [CI], 69.8 to 80.7) with trastuzumab deruxtecan and 34.1% (95% CI, 27.7 to 40.5) with trastuzumab emtansine (hazard ratio for progression or death from any cause, 0.28; 95% CI, 0.22 to 0.37; P<0.001). The percentage of patients who were alive at 12 months was 94.1% (95% CI, 90.3 to 96.4) with trastuzumab deruxtecan and 85.9% (95% CI, 80.9 to 89.7) with trastuzumab emtansine (hazard ratio for death, 0.55; 95% CI, 0.36 to 0.86; prespecified significance boundary not reached). An overall response (a complete or partial response) occurred in 79.7% (95% CI, 74.3 to 84.4) of the patients who received trastuzumab deruxtecan and in 34.2% (95% CI, 28.5 to 40.3) of those who received trastuzumab emtansine. The incidence of drug-related adverse events of any grade was 98.1% with trastuzumab deruxtecan and 86.6% with trastuzumab emtansine, and the incidence of drug-related adverse events of grade 3 or 4 was 45.1% and 39.8%, respectively. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 10.5% of the patients in the trastuzumab deruxtecan group and in 1.9% of those in the trastuzumab emtansine group; none of these events were of grade 4 or 5. CONCLUSIONS: Among patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane, the risk of disease progression or death was lower among those who received trastuzumab deruxtecan than among those who received trastuzumab emtansine. Treatment with trastuzumab deruxtecan was associated with interstitial lung disease and pneumonitis. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast03 ClinicalTrials.gov number, NCT03529110.).

A preliminary report of head-to-head comparison of 18-gene-based clinical-genomic model and oncotype DX 21-gene assay for predicting recurrence of early-stage breast cancer.

BACKGROUND: The information of Oncotype DX applied in Asian breast cancer patients is limited. A recurrence index for distant recurrence (RI-DR) has been developed for early-stage breast cancer (EBC) from tumor samples in Chinese patients. In this study, we compared the prognostic performance of the Oncotype DX (ODx) recurrence score (RS) with the RI-DR for any recurrence risk type. MATERIALS AND METHODS: One hundred thirty-eight (138) patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative EBC who were previously tested with ODx were included for testing with the RI-DR. The cutoff score to partition the low- and high-risk patients was 26 for RS and 36 for RI-DR. The primary endpoint was recurrence-free survival (RFS). RESULTS: The concordance between the RI-DR and RS was 83% in N0 patients and 81% in node-positive patients when the RS score cutoff was set at 26. With a median follow-up interval of 36.8 months, the 4-year RFS for the high- and low-risk groups categorized by the RS were 61.9% and 95.0%, respectively (hazard ratio: 10.6, 95.0% confidence interval [CI]: 1.8-62.9). The 4-year RFS in the high- and low-risk groups categorized by the RI-DR were 72.6% and 98.5%, respectively (hazard ratio: 18.9, 95% CI: 1.8-138.8). CONCLUSION: This paper illustrated the performance of RI-DR and ODx RS in breast cancer women in Taiwan. There was high concordance between the RI-DR and RS. The RI-DR is not inferior to the RS in predicting RFS in EBC patients. This study will fill the gap between the current and best practice in Chinese patients.

Risk factors and prediction model for persistent breast-cancer-related lymphedema: a 5-year cohort study.

PURPOSE: Breast-cancer-related lymphedema (BCRL) can be a transient or persistent condition. The aims of this study were to (1) identify and weigh the risk factors for persistent lymphedema (PLE) among all patients with BCRL and (2) establish a prediction model for the occurrence of PLE. METHODS: A cohort of 342 patients with BCRL with a median follow-up of 5 years after the onset of swelling was analyzed. PLE was defined as a hardening of the subcutaneous tissue, the persistence of the circumferential difference (CD) between arms, or a flare-up of swelling during follow-up. Multiple logistic regression was used to identify risk factors for PLE, including tumors, treatments, and patient-related factors. The prediction accuracy of the model was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: Of the 342 patients with BCRL, 229 (67%) had PLE. Multiple logistic regression analysis revealed that the number of lymph node metastases (p = 0.012), the maximal CD between arms at the first occurrence of swelling (p < 0.001), and the largest difference during follow-up (p < 0.001) were significant predictors for PLE. The corresponding AUC was 0.908. Although inclusion of body weight gains (p = 0.008) and maximal CD at the latest follow-up (p = 0.002) increased the analytical accuracy (AUC = 0.920), the resulting AUC values (p = 0.113) were not significantly different. CONCLUSIONS: BCRL is persistent in two thirds of patients. Patients with more lymph node metastases, weight gain, and larger CD since the onset of swelling and during follow-up have an increased likelihood of developing PLE.