Phase II Clinical Trial of Pembrolizumab and Chemotherapy Reveals Distinct Transcriptomic Profiles by Radiologic Response in Metastatic Triple-Negative Breast Cancer.

Purpose: A single arm, phase II trial of carboplatin, nab-paclitaxel, and pembrolizumab (CNP) in metastatic triple-negative breast cancer (mTNBC) was designed to evaluate overall response rate (ORR), progression-free survival (PFS), duration of response (DOR), safety/tolerability, overall survival (OS), and identify pathologic and transcriptomic correlates of response to therapy.

Patients And Methods: Patients with ≤2 prior therapies for metastatic disease were treated with CNP regardless of tumor programmed cell death-ligand 1 status. Core tissue biopsies were obtained prior to treatment initiation.

Randomized phase II trial of fulvestrant alone or in combination with bortezomib in hormone receptor-positive metastatic breast cancer resistant to aromatase inhibitors: a New York Cancer Consortium trial.

The proteasome inhibitor bortezomib enhances the effect of the selective estrogen receptor (ER) downregulator (SERD) fulvestrant by causing accumulation of cytoplasmic ER aggregates in preclinical models. The purpose of this trial was to determine whether bortezomib enhanced the effectiveness of fulvestrant. One hundred eighteen postmenopausal women with ER-positive metastatic breast cancer resistant to aromatase inhibitors (AIs) were randomized to fulvestrant alone (Arm A-500 mg intramuscular (i.

Phase II trial of patupilone in patients with brain metastases from breast cancer.

Background: For patients with progressive breast cancer brain metastasis (BCBM) after whole brain radiotherapy (WBRT), few options exist. Patupilone is an epothilone that crosses the blood-brain barrier. We hypothesized that patupilone would produce a 35% 3-month CNS progression-free survival in women with BCBM after WBRT.

MUC1 is expressed at high frequency in early-stage basal-like triple-negative breast cancer.

Triple-negative breast cancer comprises 10% to 15% of newly diagnosed breast cancer and lacks expression of the estrogen, progesterone, and human epidermal growth factor receptor 2/neu receptors. Many such tumors are basal like, a molecular intrinsic subtype of breast cancer associated with poor clinical outcomes. Patients with early-stage basal-like triple-negative breast cancer are at a high risk for relapse and may, therefore, benefit from novel therapies, including immunotherapy.

A vasculature-targeting regimen of preoperative docetaxel with or without bevacizumab for locally advanced breast cancer: impact on angiogenic biomarkers.

Purpose: Taxanes have effects on angiogenesis causing difficulties in separating biological effects of chemotherapy from those due to angiogenesis inhibitors. This randomized phase II trial was designed to evaluate the additional biomarker effect on angiogenesis when bevacizumab is added to docetaxel.

Experimental Design: Patients with inoperable breast cancer were randomized to either 2 cycles of preoperative docetaxel (D) 35 mg/m(2) i.

Optimized systemic dosing with CpG DNA enhances dendritic cell-mediated rejection of a poorly immunogenic mammary tumor in BALB/c mice.

To model a clinical trial of dendritic cell (DC) therapy of a poorly immunogenic mammary tumor, we treated BALB/c mice bearing an established TS/A mammary tumor with lysate-pulsed DCs and CpG DNA. We observed that the dose of CpG DNA required to activate DCs in vitro was insufficient to mediate tumor rejection in vivo. We therefore undertook in vivo studies to identify an optimized dose of CpG DNA for tumor therapy, defined as the lowest and least frequently administered dose of CpG DNA that mediated complete tumor rejection.

Biological therapy of breast cancer: recent clinical applications.

Advances have been made in breast cancer therapy, in both the adjuvant and metastatic settings. For example, in the adjuvant setting, genomic studies of breast cancer tissues have identified women with estrogen receptor-positive tumors who might not require chemotherapy, leading to the development of a diagnostic tool. There have also been significant developments with anticancer agents that target tumor cell surface receptors, such as HER2/neu, and those involved in angiogenesis and kinase-dependent pathways.

Phase I trial of BAY 50-4798, an interleukin-2-specific agonist in advanced melanoma and renal cancer.

Purpose: BAY 50-4798 is an analogue of interleukin-2 that selectively activates T cells over natural killer cells. This phase I study was designed to determine the maximum tolerated dose (MTD) and safety of BAY 50-4798, screen for tumor response, and assess pharmacokinetics.

Experimental Design: Forty-five patients with metastatic melanoma or renal cancer were enrolled, 31 on escalating doses to determine the MTD, with 20 renal cell carcinoma patients treated at MTD to detect antitumor activity.

Long-term survivors after gamma knife radiosurgery for brain metastases.

Background: Stereotactic radiosurgery, with or without whole-brain radiation therapy, has become a valued management choice for patients with brain metastases, although their median survival remains limited. In patients who receive successful extracranial cancer care, patients who have controlled intracranial disease are living longer. The authors evaluated all brain metastasis in patients who lived for > or = 4 years after radiosurgery to determine clinical and treatment patterns potentially responsible for their outcome.

Stereotactic radiosurgery for spinal metastases from renal cell carcinoma.

Object: The role of stereotactic radiosurgery in treating renal cell carcinoma (RCC) metastases to the spine has previously been limited. In this study the authors evaluated the clinical outcome in patients with spinal RCC who underwent single-fraction radiosurgery.

Methods: Forty-eight patients with 60 RCC metastases to the spine (six cervical, 26 thoracic, 18 lumbar, and 10 sacral) were treated with a single-fraction radiosurgery technique and were followed for a period of 14 to 48 months (median 37 months).

Evaluation of the OncoTCap (Oncology Thinking Cap) simulation in teaching medical students about clinical trials: some successes and some surprises.

Objective: A training workshop for cancer clinical trials was developed utilizing a computer simulation encompassing cancer biology, metabolism, adverse effects, and clinical trial design.

Method: Fourth-year medical students in a neoplasia elective course participated. The workshop was structured to maximize group discussions and interactions.

Enzyme-linked immunospot, cytokine flow cytometry, and tetramers in the detection of T-cell responses to a dendritic cell-based multipeptide vaccine in patients with melanoma.

A new generation of single-cell assays for measuring the frequency of peptide-specific T lymphocytes in cellular populations has become widely available. These assays, enzyme-linked immunospot (ELISPOT), cytokine flow cytometry, and tetramer binding, are used frequently for monitoring of cancer patient responses to vaccination therapies. We concomitantly used these three assays to determine the frequency of CD8(+) T cells in the circulation of 8 patients with metastatic melanoma who had received a multiepitope peptide/dendritic cell-based vaccine.

Murine dendritic cell-induced tumor apoptosis is partially mediated by nitric oxide.

Dendritic cells (DC) are potent antigen-presenting cells that are important for the priming of antitumor cytotoxic T cells. Recent reports suggest that DC may also have direct cytotoxic effector functions against selected tumor-cell lines by mechanisms that are dependent on dendritic cell-tumor cell contact in vitro. The authors report that ex vivo-generated murine DC induce the apoptosis of a panel of syngeneic and allogeneic murine tumors.