A Phase Ib Trial of Durvalumab in Combination with Trastuzumab in HER2‐Positive Metastatic Breast Cancer (CCTG IND.229)

AbstractBackground.Immune checkpoint inhibitors are active in a broad range of cancers, including programmed death ligand 1 (PD‐L1)‐positive, triple‐negative, metastatic breast cancer (MBC). Antibody‐dependent cell‐mediated cytotoxicity is a mechanism of action of trastuzumab. We performed a phase Ib trial of durvalumab and trastuzumab in HER2‐positive MBC previously treated with chemotherapy and anti‐HER2 antibodies to assess safety, efficacy, and correlative endpoints.Patients and Methods.Patients with HER2‐positive MBC were enrolled on a standard 3 + 3 design. Dose level 1 was durvalumab (1,125 mg intravenously day 1) and trastuzumab (8 mg/kg intravenously loading, then 6 mg/kg day 1) on a q3 weekly cycle. An expansion cohort at the recommended phase II dose (RP2D) performed tumor biopsies at baseline and after cycle 1. The primary endpoint was to establish the RP2D.Results.Fifteen patients were accrued from April to December 2016, of which 14 were evaluable for response. Median age was 54 years (range 40–86); the majority had visceral disease (87%) and at least three prior (adjuvant and/or metastatic) lines of chemotherapy (73%), including trastuzumab (93%), pertuzumab (60%), and trastuzumab‐emtansine (93%) for MBC. No dose‐limiting toxicities were observed at dose level 1 (n = 6) or dose expansion (n = 9) during cycle 1. One patient developed a grade ≥3 immune‐related adverse event (grade 4 diabetes mellitus). No responses by RECIST were se...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Breast Cancer Source Type: research

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This article presents a unique 3D biocompatible Aluminum-based quantum structure (QS) for in vitro cancer detection using Surface Enhanced Raman Scattering (SERS). The Al-based QSs fabricated using ultrashort pulsed laser are of two distinct surface characters, wrinkled and smooth spherical. The limit of detection for chemical sensing of Crystal Violet and Rhodamine 6G by the Al-QS was driven up to single molecule sensing (femtomolar concentration). Biological sensing of cysteine, a disease biomarker and carcinoembryonic antigen (CEA), a cancer biomarker was also tested by the Al-QS. The ability of in vitro cell detection ...
Source: Biosensors and Bioelectronics - Category: Biotechnology Source Type: research
In this study, four different weight% of Punica granatum fruit peel extract were used as green stabilizers to synthesize IONPs followed by a series of characterization experiments and in vitro anticancer evaluation. Results revealed that all synthesized IONPs have high degree of crystallinity and purity. The optimum saturation magnetization, and hydrodynamic size were found to be ∼69 emu.g−1, and 26.52 nm, respectively. Morphological studies demonstrated that adding peel extract decreased size of NPs with the average particle size below 11 nm. Cytotoxicity assay showed that the IONPs were not react...
Source: Journal of Molecular Structure - Category: Molecular Biology Source Type: research
ConclusionsDiabetes and NT-proBNP values seem to be associated with an increased risk of cardiotoxicity in breast cancer patients during trastuzumab treatment. In diabetics, glycaemic control and a more intense cardiac monitoring could provide objective benefits during the treatment. Moreover, NT-proBNP determination could become an accessible way to evaluate cardiac risk in this context.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsMLT and MTF did not show influence on pCR and objective response rates, however, MLT used during NACT may improve the quality of life.Legal entity responsible for the studyT. Semiglazova.FundingFederal State Budget Institution "National Medical Research Center of Oncology na N.N. Petrov" Ministry of Healthcare of Russian Federation.DisclosureAll authors have declared no conflicts of interest.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Abstract BACKGROUND: Immune checkpoint inhibitors are active in a broad range of cancers, including programmed death ligand 1 (PD-L1)-positive, triple-negative, metastatic breast cancer (MBC). Antibody-dependent cell-mediated cytotoxicity is a mechanism of action of trastuzumab. We performed a phase Ib trial of durvalumab and trastuzumab in HER2-positive MBC previously treated with chemotherapy and anti-HER2 antibodies to assess safety, efficacy, and correlative endpoints. PATIENTS AND METHODS: Patients with HER2-positive MBC were enrolled on a standard 3 + 3 design. Dose level 1 was durvalumab (1,125 mg intr...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
Conclusion: In the present study, in addition to known breast cancer risk factors, BMI and type 2 diabetes mellitus had an independent impact on survival of the patients, highlighting the importance of health issues such as obesity and diabetes suboptimal performance in the treatment outcomes of early breast cancer patients in Iran. PMID: 28952281 [PubMed - as supplied by publisher]
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
Nature Reviews Endocrinology 13, 251 (2017). doi:10.1038/nrendo.2017.37 Author: Conor A. Bradley A new study published in the Journal of Clinical Oncology reports that metformin improves the prognosis of patients with HER2-positive, hormone receptor (HR)-positive breast cancer and diabetes mellitus.The phase III randomized ALTTO trial included patients with early-stage, surgically resected HER2-positive breast cancer and
Source: Nature Reviews Endocrinology - Category: Endocrinology Authors: Tags: Research Highlight Source Type: research
Authors: Moreno Rosales A, Corres Molina M, Góngora Moo J, Romero Morelos P, Bandala C Abstract Background: In Mexico, breast cancer (BCa) is in first place regarding cancer mortality and has been established as a priority health issue. The incidence of metastasis from BCa is very high and presents as the principal mortality factor among women younger than 40 years of age. OBJECTIVE. To determine any associations between clinicopathological characteristics and metastasis in Mexican women under 40 years of age. Methods: During the 2010–2015 period, a total of 180 female BCa cases seen at the Navy Genera...
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
The approval of first-of-a-kind drugs rose last year to forty-one, resulting in the highest level of newly approved U.S. drugs in nineteen years. The total number of new drugs approved last year was even higher at sixty-nine. The rising figures reflect an industry-wide desire to research and develop drugs for rare and hard-to-treat diseases. The newly approved drugs serve to advance medical care and the health of patients suffering from many ailments, including various forms of cancer, heart failure, and cystic fibrosis. Additionally, more than 40% of the new therapies were approved for treatment of rare or "orphan&...
Source: Policy and Medicine - Category: American Health Authors: Source Type: blogs
Abstract Breast cancer (BC) prognosis and risk were associated to obesity, metabolic syndrome and type 2 diabetes mellitus. Two Single Nucleotide Polymorphisms (SNPs) of the adrenergic receptor-2a gene (ADRA2A): rs1800544 and rs553668, have been associated to these metabolic disorders. We investigated these SNPs in BC risk and prognosis. A total of 102 BC patients and 102 healthy controls were included. The rs1800544 and rs553668 were determined by real-time PCR. Genotypes and haplotypes frequencies between patients and controls, and for different clinico-pathologic parameters were compared. We found a significant...
Source: Pathology Oncology Research - Category: Pathology Authors: Tags: Pathol Oncol Res Source Type: research
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