Kimberly Blackwell's research while affiliated with Duke University Medical Center and other places

Publications (91)

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The METRIC study (NCT#0199733) explored a novel antibody–drug conjugate, glembatumumab vedotin (GV), targeting gpNMB that is overexpressed in ~40% of patients with triple-negative breast cancer (TNBC) and associated with poor prognosis. The study was a randomized, open-label, phase 2b study that evaluated progression-free survival (PFS) of GV compa...
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Background CLEOPATRA was a phase 3 study comparing the efficacy and safety of pertuzumab, trastuzumab, and docetaxel with placebo, trastuzumab, and docetaxel in patients with HER2-positive metastatic breast cancer. In the primary analysis and subsequent reports, progression-free and overall survival were significantly improved in the pertuzumab gro...
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Ann Oncol 2018; 29: 1541–1547 (doi: 10.1093/annonc/mdy155) The following has been added to the ‘Disclosure’ section: “CLA reports fees for advisory work with Novartis Pharmaceuticals (specifically participation on a Steering Committee for a clinical trial).”
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Purpose Brain metastases (BM) are a complication of advanced breast cancer (BC). Histology of melanoma BM offers prognostic value; however, understanding the microenvironment of breast cancer brain metastases (BCBM) is less characterized. This study reports on four histological biomarkers, gliosis, immune infiltrate, hemorrhage, necrosis, and their...
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Background: In the Mammary Oncology Assessment of LEE011's (Ribociclib's) Efficacy and Safety (MONALEESA-2) study, combination treatment with the selective inhibitor of cyclin-dependent kinases 4/6 ribociclib with letrozole significantly improved progression-free survival (PFS) versus letrozole alone in postmenopausal women with hormone receptor-p...
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The article Fulvestrant-Based Combination Therapy for Second-Line Treatment of Hormone Receptor-Positive Advanced Breast Cancer, written by Sarah Sammons, Noah S. Kornblum and Kimberly L. Blackwell, was originally published electronically on the publisher’s internet portal (currently SpringerLink).
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Background: Despite the availability of several human epidermal growth factor receptor 2 (HER2)-directed treatments, many HER2-positive (HER2+) breast cancers eventually progress because of primary or acquired resistance. Patients and methods: A 2-part, open-label, multicenter phase I/II study was conducted to determine the recommended dose of n...
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Background: The phase III MONALEESA-2 study demonstrated significantly prolonged progression-free survival (PFS) and a manageable toxicity profile for first-line ribociclib plus letrozole versus placebo plus letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer....
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p> Introduction: Breast cancer (BC) is the most commonly diagnosed cancer among women in the United States, but less than 5% of women develop BC before age 40. We sought to determine the trend over time in incidence and survival rates, and pathologic features of Non-Hispanic White (W), Non-Hispanic Black (B) and Hispanic (HIS) women (<40 years) w...
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Background: In the Phase III MONALEESA-2 study (NCT01958021), ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor [CDK4/6i]) + letrozole (LET) significantly prolonged progression-free survival (PFS) vs placebo (PBO) + LET in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advan...
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Background: Evaluation of adverse events (AEs) in pivotal registration trials and ongoing postmarketing surveillance is important for all biologics, including biosimilars. A combined analysis of two pivotal registration studies was performed to strengthen evidence on safety for biosimilar filgrastim EP2006 in patients with breast cancer receiving...
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Background: In 2015, the biosimilar filgrastim EP2006 became the first biosimilar approved by the US Food and Drug Administration (FDA) for commercial use in the United States, marketed as Zarxio®. This phase 3 randomised, double-blind registration study in patients with breast cancer receiving (neo)adjuvant myelosuppressive chemotherapy (TAC; doc...
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Background: Current treatment for HER-2+ breast cancer includes chemotherapy and targeted HER-2 therapy with trastuzumab and/or pertuzumab. Evidence is lacking on the safety of breast reconstructive operations in these patients. We hypothesized that targeted HER-2 therapy was not associated with post-mastectomy reconstructive outcomes. Study desi...
Research
516 Background: HER2 mutation occurs in ~2% of breast cancer (BC). Preclinical models suggested neratinib, an irreversible HER2/EGFR tyrosine kinase inhibitor, could be an effective treatment. This trial was conducted to assess the clinical benefit rate (CBR), defined as complete response (CR), partial response (PR) or stable disease (SD) ≥ 6 month...
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Purpose: Based on promising preclinical data, we conducted a single arm phase II trial to assess the clinical benefit rate (CBR) of neratinib, defined as complete/partial response (CR/PR) or stable disease (SD) ≥24 weeks, in HER2(mut) non-amplified metastatic breast cancer (MBC). Secondary endpoints included progression-free survival (PFS), toxici...
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Introduction: MutHER is a phase II trial that demonstrated the anti-tumor activity of the pan-HER inhibitor neratinib in mut, non-amplified MBC. The major challenges to accrue to this trial were the large number of pts to screen for the 2-3% mut population and the high rate (24%) of poor quality tumor DNA for sequencing. The goals of this ctDNA stu...
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e21701 Background: The biosimilar filgrastim Zarzio (EP2006) was approved in Europe in 2009 and in 2015 became the first biosimilar approved by the FDA for use in the USA, marketed as Zarxio. Two phase III registration studies were performed to confirm the efficacy and safety of biosimilar filgrastim in women with breast cancer receiving myelotoxic...
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10116 Background: In 2015, filgrastim EP2006 (Zarxio) became the first biosimilar approved by the FDA for commercial use in the US. This phase III randomized, double-blind registration study in patients with breast cancer receiving (neo)adjuvant myelosuppressive chemotherapy (TAC) compares US-licensed filgrastim, Neupogen (reference), with two grou...
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Background: Stereotactic radiosurgery (SRS) offers excellent local control for brain metastases (BM) with low rates of toxicity. Radiation necrosis (RN) may occur after treatment and is challenging to distinguish from local recurrence (LR). We evaluated enlarging brain lesions following SRS that were subsequently biopsied to differentiate RN versu...
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Aim: This is a pooled subgroup analysis of Asian patients enrolled in two Phase III confirmatory studies comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in women receiving chemotherapy for breast cancer. Patients & methods: Women were randomized to LA-EP2006 (n = 90) or reference (n = 84) pegfilgrastim (Neulasta(®), Amgen, I...
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Background Cyclin-dependent kinase (CDK) 4/6 inhibitor-based therapies have shown great promise in improving clinical outcomes for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer. Objectives 1. Discuss the mode of action of the three CDK4/6 inhibitors in late clinical...
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Background: Biosimilars are highly similar to a biological reference product with no clinically meaningful differences in terms of efficacy and safety. Here we present the pooled analysis of two randomized trials (PROTECT1 and 2) comparing the efficacy, safety and immunogenicity of proposed biosimilar pegfilgrastim (LA-EP2006) with reference pegfil...
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Purose We aimed to identify whether hormonal recetors change throughout tumor rogression, because this may influence management and influence rognosis in breast cancer atients. Patients and Methods From the institution's database, we collected data of 963 atients who develoed relase during their follow-us. To determine estrogen recetor(ER) and roge...
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Background: Breast cancer is the most common malignancy among women. With the introduction of improved imaging techniques and the general population's awareness of breast cancer, increasing numbers of patients are more frequently diagnosed at a very early stage. The Oncotype DX Recurrence Score (ODX) is commonly used to estimate recurrence risk and...
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Background Overexpression of fibroblast growth factor receptor 1 (FGFR1), found in ≤8% of hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2−) breast cancer cases, is correlated with decreased overall survival and resistance to endocrine therapy (ET). Dovitinib, a potent FGFR inhibitor, has demonstrated antitum...
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Therapies that efficiently induce apoptosis are likely to be required for durable clinical responses in patients with solid tumors. Using a pharmacological screening approach, we discovered that combined inhibition of B cell lymphoma-extra large (BCL-XL) and the mammalian target of rapamycin (mTOR)/4E-BP axis results in selective and synergistic in...
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Background The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2). Methods In this randomized, placebo-controlled, phase 3 trial, we evaluated...
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Purpose: Osteoclast-mediated bone resorption through src kinase releases growth factors, sustaining bone metastases. This trial determined the recommended phase II dose (RP2D) and clinical efficacy of the src kinase inhibitor dasatinib combined with zoledronic acid in bone predominant, HER2-negative breast cancer metastases. Experimental design:...
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Background Pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. In highly regulated markets, there are currently no approved biosimilars of pegfilgrastim. Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2) was a confirmatory efficacy and safety study designed to co...
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Brain metastases represent the most common type of brain tumor. These tumors offer a dismal prognosis and significantly impact quality of life for patients. Their capacity for central nervous system (CNS) invasion is dependent upon induced disruptions to the blood brain barrier, alterations to the brain microenvironment, and mechanisms for escaping...
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Aim: This randomized, double-blind trial compared proposed biosimilar LA-EP2006 with reference pegfilgrastim in women receiving chemotherapy for breast cancer (PROTECT-1). Patients & methods: Women (≥18 years) were randomized to receive LA-EP2006 (n = 159) or reference (n = 157) pegfilgrastim (Neulasta(®), Amgen) for ≤6 cycles of (neo)-adjuvant...
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Background: Baseline TIL density and T-cell clonality predict pathological complete response (pCR) to neoadjuvant (NA) trastuzumab (TRAS). Preclinical data suggests that a major mechanism of TRAS is enhancement of antibody-dependent cytoxicity (ADCC) and T-cell mediated tumor kill and that the combination of TRAS with pertuzumab (PERT) may enhance...
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Background: An abbreviated pathway for biological products shown to be biosimilar to the reference product exists in Europe and the US. The randomized PROTECT1 trial compared the efficacy and safety of the proposed biosimilar pegfilgrastim with reference pegfilgrastim. Methods: In this multinational, prospective, double-blind trial, chemotherapy-na...
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Background: Tumor DNA sequencing is now readily available in metastatic breast cancer (MBC). The purpose of this study was to determine the effect of molecular testing on clinical decision-making in MBC at an academic cancer center. Methods: We obtained the Foundation One (FO) tests that were requested from Duke Cancer Institute breast oncologists...
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Purpose: Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatme...
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There is growing interest in the relationship between dietary habits and cancer. Dietary fibers are a complex group of oligosaccharides, polysaccharides, resistant starch, and resistant dextrins. There is longstanding evidence that dietary fibers may reduce circulating estrogen levels through changes in the gut microbiome and increased excretion of...
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Leptomeningeal disease has become increasingly prevalent as novel therapeutic interventions extend the survival of cancer patients. Although a majority of leptomeningeal spread occurs secondary to breast cancer, lung cancer, and melanoma, a wide variety of malignancies have been reported as primary sources. Symptoms on presentation are equally dive...
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Biosimilars of filgrastim are in widespread clinical use in Europe. This phase III study compares biosimilar filgrastim (EP2006), with the US-licensed reference product, Neupogen(®), in breast cancer patients receiving (neo)adjuvant myelosuppressive chemotherapy (TAC). A total of 218 patients receiving 5 µg/kg/day filgrastim over 6 chemotherapy cyc...
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Zoledronic acid, a potent nitrogen-containing bisphosphonate, plays a key role in preventing complications of bone metastases in metastatic breast cancer, but its affect on early-stage breast cancer has been unclear. The preclinical data supporting the anticancer effects of zoledronic acid are compelling and several recent clinical trials have sugg...
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Introduction: Biosimilars are biologics which have demonstrated highly similar safety, potency and purity to an originator product. Several biosimilars of recombinant human filgrastim, based on the originator Neupogen®, have become available in Europe since 2008 and are now in clinical use for the prevention of chemotherapy-induced neutropenia and...
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Next generation sequencing (NGS) coupled with sophisticated bioinformatics tools yields an unprecedented amount of information regarding tumor genetics, with the potential to reveal insights into tumor behavior. NGS and other multiplex genomic assays are rapidly spilling from the laboratory into the clinic through numerous commercial and academic e...
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Background: PIK3CA is one of the most frequently mutated genes in human breast cancer, and the high expression of a PIK3CA-pathway signature is associated with the poor prognosis Luminal B and Basal-like expression subtypes. BKM120 is an oral pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, which has shown activity in preclinical and ear...
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Background: 1/3 of women with metastatic HER2+ breast cancer will develop central nervous system (CNS) metastases yet evidence-based treatments for women with progressive CNS disease are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4 which has promising activity in HER2+ breast cancer. Preclinical evidence suggests it may...
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TPS1148 Background: Overcoming endocrine resistance is a critical goal in the treatment of hormone receptor−positive (HR+) breast cancer. Molecular mechanisms associated with endocrine resistance include adaptive “cross-talk” between the estrogen receptor and the fibroblast growth factor receptor (FGFR). Up to 8% of HR+/HER2- breast cancer patients...
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2041 Background: aBC, a small heat shock protein, is commonly expressed in basal BC and predicts poor survival in BC patients (pts). aBC has been associated with the development of BM within basal BC. We evaluated the expression of aBC in BM and pBC with eventual BM and its association with survival. Methods: Under IRB approval (UNC/Duke), we estab...
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TPS122 Background: Patients with ER-/PR- MBC do not benefit from endocrine therapy. Doane et al. described a subgroup of ER-/PR- breast cancers with a gene expression profile similar to ER+ tumors but characterized by AR expression (Oncogene 2006). Farmer et al. identified an AR+ER-, non-basal-like group of breast tumors in a separate data set and...
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TPS127 Background: TNBC is an aggressive subset of BC with high rates of BM and poor survival. Iniparib, an anticancer agent with poly (ADP-ribose) polymerase (PARP) inhibitory activity, in combination with DNA-damaging chemotherapy appears to be effective in advanced TNBC. Iniparib penetrates the blood brain barrier. We are evaluating the efficacy...
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Background: Preclinical data suggest that inhibition of the EGFR and HER2 growth factor signaling pathways might potentiate the efficacy of endocrine treatment for ER positive breast cancer. CALGB 40302 was designed to determine whether the addition of the dual-kinase inhibitor, lapatinib, would improve progression-free survival (PFS) among women w...
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1109 Background: Improved therapies and predictive markers are needed in TNBC. B (bevacizumab) and C combinations are active in many solid tumors, including TNBC. SPARC is an albumin-binding protein secreted by tumors, a potential target of nabP. This study used enrollment metastatic biopsies (bxs) of TNMBC to 1) determine intratumor SPARC expressi...
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e21040 Background: SPARC is an albumin-binding protein associated with poor prognosis that may mediate intratumoral accumulation of nab-P. SPARC is associated with both tumor cells and stromal components. We examined SMS in paired primary (P) and metastatic (M) TNBC biopsies (bxs) to 1) determine changes in expression, and 2) examine potential corr...
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#3123 Background: In order to optimize drug efficacy and patient selection for targeted agents such as dasatinib, a tyrosine kinase inhibitor, there is a need for adaptive trial methodologies and validated marker endpoints. Predictive and pharmacodynamic (PD) biomarkers of dasatinib activity will be crucial for individualized drug dosing and enrich...
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3517 Background: Radiation activates HIF-1a via a free radical mediated mechanism associated with reoxygenation. This response could be inhibited, resulting in reduced tumor vascularity and proliferation. Preclinical breast cancer models and a Phase Ib clinical trial (CT) were employed to look at the effects of chemo with or without an oral HIF-1a...