Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Guideline Update.

PURPOSE: The aim of this work is to update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. METHODS: An Expert Panel conducted a targeted systematic literature review guided by a signals approach to identify new, potentially practice-changing data that might translate into revised guideline recommendations. RESULTS: The Expert Panel reviewed abstracts from the literature review and identified one article for inclusion that reported results of the phase III, open-label KATHERINE trial. In the KATHERINE trial, patients with stage I to III human epidermal growth factor receptor 2 (HER2)-positive breast cancer with residual invasive disease in the breast or axilla after completing neoadjuvant chemotherapy and HER2-targeted therapy were allocated to adjuvant trastuzumab emtansine (T-DM1; n = 743) or to trastuzumab (n = 743). Invasive disease-free survival was significantly higher in the T-DM1 group than in the trastuzumab arm (hazard ratio, 0.50; 95% CI, 0.39 to 0.64; P < .001), and risk of distant recurrence was lower in patients who received T-DM1 than in patients who received trastuzumab (hazard ratio, 0.60; 95% CI, 0.45 to 0.79). Grade 3 or higher adverse events occurred in 190 patients (25.7%) who received T-DM1 and in 111 patients (15.4%) who received trastuzumab. RECOMMENDATIONS: Patients with HER2-positive breast cancer with pathologic invasive residual disease at surgery after standard preoperative chemotherapy and HER2-targeted therapy should be offered 14 cycles of adjuvant T-DM1, unless there is disease recurrence or unmanageable toxicity. Clinicians may offer any of the available and approved formulations of trastuzumab, including trastuzumab, trastuzumab and hyaluronidase-oysk, and available biosimilars.Additional information can be found at www.asco.org/breast-cancer-guidelines.

Minimal residual disease negativity and lenalidomide maintenance therapy are associated with superior survival outcomes in multiple myeloma.

Modern combinations of therapies for multiple myeloma have led to improvement in survival outcomes with near 100% overall response rate and 25% complete response rates, particularly with autologous hematopoietic cell transplant (AHCT). Minimal residual disease (MRD) assessment with multiparameter flow cytometry is a valid prognostic biomarker for progression-free survival (PFS) and overall survival (OS). However, few data exist regarding whether MRD positivity or negativity will meaningfully influence treatment decisions. We evaluated 433 patients who received induction therapy, followed by AHCT. Participants had MRD assessment by multiparameter flow cytometry before and at days +100 and +365 following AHCT. They also received either lenalidomide, bortezomib, or no maintenance therapy following AHCT. Maintenance treatment with lenalidomide improved MRD negativity at day +365 compared to bortezomib (92.9% vs 41.6%, p = 0.01), or no maintenance therapy (92.9% vs 24.4%, p = 0.012). The median PFS for patients who were MRD negative at day + 365 was 42 vs 17.5 months (p < 0.001) and median OS was 80.6 vs 59 months (p = 0.02). Maintenance therapy following AHCT for multiple myeloma improves the depth of response as assessed by MRD.

Optimizing particle-mediated epidermal delivery of an influenza DNA vaccine in ferrets.

Particle-mediated DNA delivery technologies ("gene guns") have been shown in both animal and clinical studies to be an effective means of increasing the immunogenicity and protective efficacy of DNA vaccines. The primary goal in optimizing particle-mediated epidermal delivery (PMED) vaccination in different animal models is to achieve delivery of DNA-coated gold beads into the viable epidermis. Two key para-meters that influence this outcome include the delivery pressure, which controls the penetrative force of the beads into the skin, and the anatomical site of DNA delivery. Although the ferret has been extensively used as an experimental model for influenza infection in humans, very few studies have investigated the capacity for PMED DNA vaccination to induce protective immune responses in ferrets. Here we describe methods to optimize DNA vaccine delivery using the PowderJect XR1 gene delivery in ferrets. We first assess the effects of firing pressure on both the delivery of DNA-coated gold beads into the desired epidermal layer and the degree of DNA vaccine reporter gene expression at the target site. Second, we evaluate the impact of vaccination site (skin or tongue) on DNA vaccine immunogenicity by measuring serum antibody responses to the model antigens influenza virus hemagglutinin and hepatitis B core antigen. Results from these studies support the use of the PowderJect XR1 device in ferrets for the study of prophylactic and therapeutic DNA vaccines against clinically important diseases such as influenza virus infection.