Minimal clinical benefit of single agent Orathecin (Rubitecan) in heavily pretreated metastatic breast cancer

2005 ◽  
Vol 57 (4) ◽  
pp. 540-544 ◽  
Author(s):  
Silwan Chedid ◽  
Edgardo Rivera ◽  
Debbie K. Frye ◽  
Nuhad Ibrahim ◽  
Francisco Esteva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Benefit ◽  
Single Agent ◽  
Metastatic Breast ◽  
Heavily Pretreated

A pilot study utilizing molecular profiling to find potential targets and select individualized treatments for patients with metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS11123-TPS11123 ◽  
Author(s):  
Gayle S. Jameson ◽  
Emanuel Petricoin ◽  
Jasgit C. Sachdev ◽  
Lance A. Liotta ◽  
David Loesch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Pilot Study ◽  
Clinical Benefit ◽  
Metastatic Breast ◽  
Molecular Profiling ◽  
Treatment Selection ◽  
Mapping Technique ◽  
Type I ◽  
Heavily Pretreated

TPS11123 Background: The objective of this prospective pilot study was to determine if treatment selected by molecular profiling (MP) of metastatic breast cancer (MBC) tumors at time of disease progression provides greater clinical benefit than empiric treatment selection. Methods: Eligible pts had MBC, ≥ 3 prior lines of therapy, and > 6 wks - < 6 months time to progression on last treatment prior to study entry. Fresh core biopsy samples were taken from the metastatic site for MP. Analysis by IHC, FISH, DNA microarray and reverse phase protein microarray (RPMA) a quantitative protein pathway activation mapping technique using laser capture micro dissected tumor cells was done, with results in ≤14 days reviewed by a Treatment Selection Committee. The primary objective was to compare the progression-free survival (PFS) using a MP selected treatment regimen to the preceding PFS. Clinical benefit for the pt is defined by PFS ratio (PFS on MP selected therapy/PFS on prior therapy) is ≥ 1.3, (JCO,28:4877-83:2010). N= 25 was determined (exact single-stage design for phase II studies, type I error rate of 5% [one-sided], power of 90%). MP selected therapy would warrant further investigation if ≥ 35% of the pts demonstrate a PFS ratio of ≥ 1.3. Results: Three U.S. sites enrolled 25 evaluable pts who were treated based on MP results. Pts were heavily pretreated with 4 -11 prior therapies (median 7.24). Ten pts (40%) met or exceeded the PFS ratio of 1.3. The most common targets used in drug treatment selection were TOPO1, TS, ER/PR, TOP2A, HER2. Sixty percent of pts’ samples had activation of drug targets determined by RPMA in 3 major clusters: pan-HER-AKT; EGFR/SRC/ERK/mTOR; IGFR/RAF/MEK/PLK1. Days on MP selected treatments range from 9 - 816+. 3 pts continue on treatment for 199, 254 and 816 days. Conclusions: This study demonstrates the feasibility of a highly multiplexed genomic and proteomic MP study for treatment selection in a timely fashion. Patient-specific target driven treatment selection based on MP of a metastatic lesion provided clinical benefit for 10 of 25 heavily pretreated MBC pts. Thus, this approach merits further investigation in future studies. Funded by The Side-Out Foundation. Clinical trial information: NCT01074814.

Phase II Evaluation of Thalidomide in Patients With Metastatic Breast Cancer

2000 ◽  
Vol 18 (14) ◽  
pp. 2710-2717 ◽  
Author(s):  
Said M. Baidas ◽  
Eric P. Winer ◽  
Gini F. Fleming ◽  
Lyndsay Harris ◽  
James M. Pluda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Progressive Disease ◽  
Single Agent ◽  
Metastatic Breast ◽  
Complete Response ◽  
Pharmacokinetic Studies ◽  
Angiogenic Growth Factors ◽  
Heavily Pretreated ◽  
Dose Levels

PURPOSE: To determine the efficacy, safety, pharmacokinetics, and effect on serum angiogenic growth factors of two dose levels of thalidomide in patients with metastatic breast cancer. PATIENTS AND METHODS: Twenty-eight patients with progressive metastatic breast cancer were randomized to receive either daily 200 mg of thalidomide or 800 mg to be escalated to 1,200 mg. Fourteen heavily pretreated patients were assigned to each dose level. Each cycle consisted of 8 weeks of treatment. Pharmacokinetics and growth factor serum levels were evaluated. RESULTS: No patient had a true partial or complete response. On the 800-mg arm, 13 patients had progressive disease at or before 8 weeks of treatment and one refused to continue treatment. The dose was reduced because of somnolence to 600 mg for five patients and to 400 mg for two and was increased for one to 1,000 mg and for four to 1,200 mg. On the 200-mg arm, 12 patients had progressive disease at or before 8 weeks and two had stable disease at 8 weeks, of whom one was removed from study at week 11 because of grade 3 neuropathy and the other had progressive disease at week 16. Dose-limiting toxicities included somnolence and neuropathy. Adverse events that did not require dose or schedule modifications included constipation, fatigue, dry mouth, dizziness, nausea, anorexia, arrhythmia, headaches, skin rash, hypotension, and neutropenia. Evaluation of circulating angiogenic factors and pharmacokinetic studies failed to provide insight into the reason for the lack of efficacy. CONCLUSION: Single-agent thalidomide has little or no activity in patients with heavily pretreated breast cancer. Further studies that include different patient populations and/or combinations with other agents might be performed at the lower dose levels.

scholarly journals Real-world survival outcomes of heavily pretreated patients with refractory HR+, HER2−metastatic breast cancer receiving single-agent chemotherapy—a comparison with MONARCH 1

2020 ◽  
Vol 184 (1) ◽  
pp. 161-172
Author(s):  
Hope S. Rugo ◽  
Veronique Dieras ◽  
Javier Cortes ◽  
Debra Patt ◽  
Hans Wildiers ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real World ◽  
Single Agent ◽  
Metastatic Breast ◽  
Clinical Context ◽  
Eligibility Criteria ◽  
The Real ◽  
Heavily Pretreated ◽  
Single Agent Chemotherapy

Abstract Purpose In MONARCH 1 (NCT02102490), single-agent abemaciclib demonstrated promising efficacy activity and tolerability in a population of heavily pretreated women with refractory HR+, HER2− metastatic breast cancer (MBC). To help interpret these results and put in clinical context, we compared overall survival (OS) and duration of therapy (DoT) between MONARCH 1 and a real-world single-agent chemotherapy cohort. Methods The real-world chemotherapy cohort was created from a Flatiron Health electronic health records-derived database based on key eligibility criteria from MONARCH 1. The chemotherapies included in the cohort were single-agent capecitabine, gemcitabine, eribulin, or vinorelbine. Results were adjusted for baseline demographics and clinical differences using Mahalanobis distance matching (primary analysis) and entropy balancing (sensitivity analysis). OS and DoT were analyzed using the Kaplan–Meier method and Cox proportional hazards regression. Results A real-world single-agent chemotherapy cohort (n = 281) with eligibility criteria similar to the MONARCH 1 population (n = 132) was identified. The MONARCH 1 (n = 108) cohort was matched to the real-world chemotherapy cohort (n = 108). Median OS was 22.3 months in the abemaciclib arm versus 13.6 months in the matched real-world chemotherapy cohort with an estimated hazard ratio (HR) of 0.54. The median DoT was 4.1 months in MONARCH 1 compared to 2.9 months in the real-world chemotherapy cohort with HR of 0.76. Conclusions This study demonstrates an approach to create a real-world chemotherapy cohort suitable to serve as a comparator for trial data. These exploratory results suggest a survival advantage and place the benefit of abemaciclib monotherapy in clinical context.

Vorinostat to restore sensitivity to aromatase inhibitor therapy in metastatic breast cancer: A phase II clinical trial with ER imaging correlates.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS3109-TPS3109
Author(s):  
Hannah M. Linden ◽  
Brenda F Kurland ◽  
Jeanne Link ◽  
Vijayakrishna K. Gadi ◽  
Jennifer M. Specht ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Aromatase Inhibitor ◽  
Clinical Benefit ◽  
Fdg Pet ◽  
Single Agent ◽  
Metastatic Breast ◽  
Receptor Modulation ◽  
The Impact ◽  
Er Expression

TPS3109 Background: Endocrine refractory,Indolent, soft tissue, and bone dominant metastatic breast cancer is a clinical problem, for which alternatives to chemotherapy are needed, Histone deacetylace inhibitors (HDACi) have shown pre-clinical promise in estrogen receptor-modulation and restoring sensitivity to endocrine manipulation, suggesting potential clinical benefit. HDACi restore ER expression in ER-negative cells which are then sensitive to AI treatment in xenografts (Sabnis 2011) and are toxic to ER-positive cell lines (Huang 2000). Vorinostat is an FDA approved HDACi for CTCL, and could have a beneficial role in restoring ER-signaling in endocrine-resistant tumors. We hypothesized that HDACi therapy could restore sensitivity to aromatase inhibitor (AI) therapy, in patients with prior progression on AI, and allow continued endocrine therapy. Recent data suggest clinical benefit of Tamoxifen and vorinostat given continuously (Munster 2011) as well as entinostat and an AI (Yardley 2011). Our prior work has shown the feasibility of monitoring regional ER expression and ER-estrogen binding in vivo using [F-18]fluoroestradiol (FES) PET imaging (Linden 2011) providing a biomarker to interrogate the molecular target. Methods: Patients with metastatic breast cancer with prior clinical benefit from endocrine manipulation who progressed on AI therapy are eligible. Patients must be off ER blocking therapies, and functionally postmenopausal. Baseline FES and FDG PET are performed and patients receive investigational vorinostat treatment at 400 mg po BID for 2 weeks followed by serial FES and FDG PET to assess the impact of vorinostat on ER expression and tumor metabolism. Patients are retreated on their prior AI as a single agent for 6 weeks, followed by paired FES and FDG and clinical assessment. Patients with clinical benefit may continue on treatment: 2 weeks of vorinostat followed by 6 weeks of AI in 8-week cycles until progressive disease or toxicity. We have enrolled 4 of a planned 20 patients.

scholarly journals Hormone receptor–positive, HER2-negative metastatic breast cancer: redrawing the lines

2018 ◽  
Vol 25 ◽  
pp. 131 ◽  
Author(s):  
A. Matutino ◽  
A.A. Joy ◽  
C. Brezden-Masley ◽  
S. Chia ◽  
S. Verma
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Benefit ◽  
Hormone Receptor ◽  
Single Agent ◽  
Treatment Algorithm ◽  
Metastatic Breast ◽  
Standards Of Care ◽  
Endocrine Treatment ◽  
Hormone Receptor Positive

Estrogen receptor modulators and estrogen deprivation have become standards of care for hormone receptor– positive metastatic breast cancer. However, after traditional first-line endocrine monotherapy treatment, the disease typically progresses despite the initial high rate of clinical benefit. Multiple studies have aimed at optimizing treatment strategies to improve upon clinical benefit beyond the traditional single-agent endocrine treatment. With the availability of new data and novel therapies, the clinical practice challenge becomes how best to define the optimal treatment sequence to maximize clinical benefit. In this review, we present treatment options clinically relevant to the management of hormone-positive, her2-negative metastatic breast cancer, and we propose a treatment algorithm based on the current literature.

scholarly journals PO67 CLINICAL BENEFIT OF ETHINYLESTRADIOL AS A SALVAGE ENDOCRINE THERAPY FOR THE HEAVILY PRETREATED METASTATIC BREAST CANCER

The Breast ◽  
2013 ◽  
Vol 22 ◽  
pp. S43
Author(s):  
Hirotaka Iwase ◽  
Naoto Kondo ◽  
Toshinari Yamashita ◽  
Seigo Nakamura ◽  
Masahiko Ikeda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Clinical Benefit ◽  
Metastatic Breast ◽  
Heavily Pretreated

scholarly journals Phase II Studies of Gemcitabine and Cisplatin in Heavily and Minimally Pretreated Metastatic Breast Cancer

2009 ◽  
Vol 27 (13) ◽  
pp. 2163-2169 ◽  
Author(s):  
Helen K. Chew ◽  
James H. Doroshow ◽  
Paul Frankel ◽  
Kim A. Margolin ◽  
George Somlo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Genetic Polymorphisms ◽  
Phase Ii ◽  
Response Rate ◽  
Single Agent ◽  
Metastatic Breast ◽  
High Dose ◽  
Phase Ii Trials ◽  
Heavily Pretreated

Purpose Cisplatin and gemcitabine have single-agent activity in metastatic breast cancer, and preclinical data support synergy of the combination. Two parallel, phase II trials were conducted to evaluate the response rate, response duration, and toxicities of the combination. Genetic polymorphisms were analyzed for correlation with outcomes. Patients and Methods Eligible women had measurable disease and heavily or minimally pretreated metastatic breast cancer. The heavily pretreated protocol required prior anthracycline and taxane therapy; cisplatin as part of high-dose therapy was allowed. All patients received cisplatin 25 mg/m2 on days 1 through 4 and gemcitabine 1,000 mg/m2 on days 2 and 8 of a 21-day cycle with prophylactic granulocyte colony-stimulating factor in the heavily pretreated group. Sera from a subset of patients were evaluated by polymerase chain reaction restriction fragment length polymorphism for polymorphisms in 10 genes of interest. Results Of 136 women enrolled, 74 were heavily pretreated. Both protocols accrued to their two-stage design. The response rate for both the heavily and minimally pretreated cohorts was 26%, and the median durations of response were 5.3 and 5.9 months, respectively. In a multivariate analysis, hormone receptor–negative disease was associated with a higher response rate. The most common grades 3 or 4 toxicities were thrombocytopenia (71%), neutropenia (66%), and anemia (38%). In a subset of 55 patients, the xeroderma pigmentosum group D (XPD)–751, x-ray cross-complementing group 3 (XRCC3) and cytidine deaminase polymorphisms were significantly associated with clinical outcomes. Conclusion Combination cisplatin and gemcitabine is active in metastatic breast cancer regardless of prior therapy. Genetic polymorphisms may tailor which patients benefit from this regimen.

Study of lapatinib (T) in combination with trastuzumab (T) in women heavily pretreated with HER2-positive metastatic breast cancer (MBC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11577-e11577 ◽  
Author(s):  
Javier Salvador ◽  
Manuel Ruiz Borrego ◽  
Maria Valero ◽  
Juan L. Bayo ◽  
Luis De La Cruz-Merino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Benefit ◽  
Kinase Inhibitor ◽  
Antitumour Activity ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Heavily Pretreated ◽  
Grade 3

e11577 Background: The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer.In heavily pre-treated pts, L+T is associated with improved outcomes compared to L alone and significantly improved progression-free survival (PFS), offering a chemotherapy-free option for patients with heavily pretreated human epidermal growth factor. (Kimberly L et al, 2012 JCO). Methods: We evaluated the safety and efficacy of L+T in patients with 1-4 prior (Median 3) lines of chemotherapy (CT) for HER2+ MBC.: 20 Pts with measurable, HER2+ MBC were eligible. Pts received every 3 weeks T (8 mg/kg loading then 6 mg/Kg) and daily L 1000 mg. Results: The characteristic of the all of pts included (20) are: median age 51.4 (32-68) Total number of cycles administered was 141. The median cycles administered per pts was 6 (range 1-18). Median follow-up was 6 months. Of the 18 pts with response assessment, the clinical benefit obtained was: 76,1% (5,9% PR + and 70,6% disease stabilization) with 95% CI 71.3%-80.9%. Disease progression was 17,6%. Of the 20 pts with a median follow up of 13,32 m (3-32), median PFS for these pts was 6 m. The one year OS % was 64,70% (56,7-72,7). All pts had received al least one line lapatinib prior (1-3). Toxicity was generally manageable. No major cardiac dysfunctions ocurred. Grade 3/4 treatment-related toxicities were uncommon (grade 3 diarrhea, 18%; grade 3 hepatic 7%. All others < 3 %). Conclusions: L+T is an active regimen in HER2+ MBC. L+T showed high clinical benefit with manageable safety profile. Dual inhibition of HER2 might be a valid approach to treatment of Her-2 positive metastatic breast cancer.

Efficacy and Safety of Trastuzumab as a Single Agent in Heavily Pretreated Patients with Her-2/NEU-Overexpressing Metastatic Breast Cancer

2004 ◽  
Vol 90 (1) ◽  
pp. 40-43 ◽  
Author(s):  
Masataka Sawaki ◽  
Yoshinori Ito ◽  
Keiichiro Tada ◽  
Nobuyuki Mizunuma ◽  
Shunji Takahashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Single Agent ◽  
Metastatic Breast ◽  
Efficacy And Safety ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Her 2
Sign in / Sign up

Export Citation Format

Share Document