Results from the randomized KEYNOTE-355 study of pembrolizumab plus chemotherapy for Asian patients with advanced TNBC.

In the phase 3 KEYNOTE-355 study (NCT02819518), pembrolizumab plus chemotherapy demonstrated statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) versus placebo plus chemotherapy among patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) and programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 10 tumors. We analyzed outcomes for the subgroup of patients enrolled in Asia in KEYNOTE-355. Patients received pembrolizumab 200 mg or placebo (2:1 randomization) every 3 weeks for 35 cycles plus investigator's choice chemotherapy.

Pembrolizumab plus chemotherapy for first-line treatment of advanced triple-negative breast cancer.

A systematic review and network meta-analysis (NMA) was performed to evaluate the efficacy of first-line treatments for locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) patients. Databases were searched for randomized controlled trials evaluating first-line treatments for locally recurrent unresectable or metastatic TNBC patients. NMA was performed to estimate relative treatment effects on overall and progression-free survival between pembrolizumab + chemotherapy and other interventions.

Neoadjuvant immunotherapy and chemotherapy regimens for the treatment of high-risk, early-stage triple-negative breast cancer: a systematic review and network meta-analysis.

Background: Patients with triple-negative breast cancer (TNBC) are generally younger and more likely to experience disease recurrence and have the shortest survival among all breast cancer patients. Recently, neoadjuvant delivery of the programmed cell death protein-1 inhibitor pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab was approved for patients with high-risk, early-stage TNBC, but this treatment regimen has not been evaluated in head-to-head trials with other neoadjuvant treatment regimens. Therefore, the objective of this study was to estimate the relative efficacy of neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab versus other neoadjuvant treatments for early-stage TNBC through a systematic review and network meta-analysis (NMA).

Association between event-free survival and overall survival in early-stage triple-negative breast cancer.

This study evaluated event-free survival (EFS) as a surrogate outcome for overall survival (OS) in neoadjuvant therapy for early-stage triple-negative breast cancer (eTNBC). Meta-regression analyses based on a targeted literature review were used to evaluate the individual- and trial-level associations between EFS and OS. In the individual-level analyses, 3-year EFS was a significant predictor of 5-year OS (p < 0.

Pembrolizumab plus chemotherapy in Japanese patients with triple-negative breast cancer: Results from KEYNOTE-355.

Pembrolizumab plus chemotherapy improved progression-free survival (PFS) and overall survival (OS) compared with placebo plus chemotherapy in patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer with tumor programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥10 in the global, phase 3, randomized controlled trial KEYNOTE-355. We report results for patients enrolled in Japan. Patients were randomized 2:1 to pembrolizumab 200 mg or placebo Q3W for 35 cycles plus chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin).

Cost-Effectiveness of Neoadjuvant Pembrolizumab Plus Chemotherapy Followed by Adjuvant Single-Agent Pembrolizumab for High-Risk Early-Stage Triple-Negative Breast Cancer in the United States.

Introduction: The randomized phase III KEYNOTE-522 trial demonstrated that addition of pembrolizumab to neoadjuvant chemotherapy provided a significant improvement in event-free survival and a favorable trend in overall survival for high-risk early-stage triple-negative breast cancer (eTNBC). This analysis evaluated the cost-effectiveness of pembrolizumab in combination with chemotherapy as neoadjuvant treatment and continued as a single-agent adjuvant treatment after surgery vs. neoadjuvant chemotherapy for patients with high-risk eTNBC in the USA.

Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1.

Objective: In the KEYNOTE-355 (KN355) trial, pembrolizumab in combination with chemotherapy demonstrated superior efficacy and manageable safety compared with chemotherapy alone in patients with previously untreated locally recurrent inoperable and metastatic triple-negative breast cancer (mTNBC) with PD-L1 positive (Combined Positive Score [CPS]≥ 10) tumours. This study aimed to evaluate the clinical benefits and risks of pembrolizumab measured by quality-adjusted survival in the trial population.

Methods: The study used data from the final analysis of KN355.

Cost-effectiveness of pembrolizumab plus chemotherapy as first-line treatment in PD-L1-positive metastatic triple-negative breast cancer.

This study evaluated the cost-effectiveness of pembrolizumab/chemotherapy combinations for previously untreated metastatic triple-negative breast cancer patients in the USA with PD-L1 combined positive score ≥10. A partitioned-survival model was developed to project health outcomes and direct medical costs over a 20-year time horizon. Efficacy and safety data were from randomized clinical trials.

Outcomes and patterns of care in a nationwide cohort of pediatric medulloblastoma: Factors affecting proton therapy utilization.

Purpose: We examined national outcomes and patterns of care for pediatric patients with medulloblastoma (MB) in a large observational cohort.

Methods And Materials: Using the National Cancer Database, we evaluated the clinical features and survival outcomes of patients diagnosed with MB. The association between intervention, covariables, and outcome was assessed in a multivariable Cox analysis and through logistic regression analysis.

Impact of Required Versus Self-Directed Use of Virtual Patient Cases on Clerkship Performance: A Mixed-Methods Study.

Purpose: To explore how students use and benefit from virtual patient cases (VPCs).

Method: In academic years 2013-2014 and 2014-2015, cohorts of students in pediatrics (Peds), family medicine (FM), and internal medicine (IM) clerkships were allocated to either core required use (CRU) or self-directed use (SU) of MedU VPCs. Outcomes included number and time of case review, student perception of learning from VPCs, National Board of Medical Examiners (NBME) subject examination scores, and summative clinical ratings for medical knowledge and differential diagnoses/problem solving.

A Stroke Mimic: Methotrexate-induced Neurotoxicity in the Emergency Department.

Background: Acute lymphoblastic leukemia (ALL) is the most common form of childhood leukemia. The treatment of ALL involves multimodality therapy, and methotrexate (MTX) remains a mainstay of treatment. A complication of MTX therapy includes acute, subacute, and chronic neurotoxocity.

A phase II trial of a multi-agent oral antiangiogenic (metronomic) regimen in children with recurrent or progressive cancer.

Background: Preclinical models show that an antiangiogenic regimen at low-dose daily (metronomic) dosing may be effective against chemotherapy-resistant tumors. We undertook a prospective, open-label, single-arm, multi-institutional phase II study to evaluate the efficacy of a "5-drug" oral regimen in children with recurrent or progressive cancer.

Procedure: Patients ≤21 years old with recurrent or progressive tumors were eligible.

Pediatric primary bone lymphoma-diffuse large B-cell lymphoma: morphologic and immunohistochemical characteristics of 10 cases.

Most primary bone lymphomas (PBLs) are diffuse large B-cell lymphomas (DLBCLs). Pediatric PBL-DLBCL has a favorable prognosis but remains poorly characterized. Herein, 10 such cases are detailed.