A comparative effectiveness analysis of single-agent cytotoxics in triple-negative metastatic breast cancer (TN-MBC) patients.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e17648-e17648
Author(s):  
George Dranitsaris ◽  
Hope S. Rugo ◽  
Stefan Gluck ◽  
David Cox ◽  
Claudio Faria
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Comparative Effectiveness ◽  
Triple Negative ◽  
Single Agent ◽  
Metastatic Breast ◽  
Effectiveness Analysis ◽  
Comparative Effectiveness Analysis

A comparative effectiveness analysis of single-agent cytotoxics in triple-negative metastatic breast cancer patients.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 157-157
Author(s):  
George Dranitsaris ◽  
Stefan Glück ◽  
Claudio Faria ◽  
David Cox ◽  
Hope S. Rugo
Keyword(s):  
Propensity Score ◽  
Comparative Effectiveness ◽  
Triple Negative ◽  
Performance Status ◽  
Single Agent ◽  
Cytotoxic Agents ◽  
Current Therapy ◽  
Effectiveness Analysis ◽  
Community Oncology ◽  
Comparative Effectiveness Analysis

157 Background: There has been considerable progress in treatments for MBC. However, the identification of optimal cytotoxic agents in patients with triple negative disease (negative for hormone receptors, ER/PR and HER-2) remains a therapeutic challenge. A comparative effectiveness analysis of four cytotoxic agents was conducted in patients with TN MBC. Methods: We retrospectively identified 225 patients treated with single agent eribulin (E=47), capecitabine (C=69), gemcitabine (G=56) or vinorelbine (V=53) in 19 community oncology clinics across the US. Data collection included baseline patient characteristics, performance status, duration of current therapy, growth factor use and all dose limiting toxicities. Time to treatment failure (TTF) was measured from the first cycle of chemotherapy until disease progression, discontinuation due to toxicity, or death. TTF was then estimated using the Kaplan-Meier method and Cox proportional hazard modeling adjusted for clustering on the practice site. To control for selection bias that is inherent in observational studies, a propensity score weighted TTF analysis was also conducted. Results: Patients were comparable with respect to age, performance status, duration of disease free survival, presence of comorbidities and hemoglobin level prior to the start of chemotherapy. However, the median lines of therapy for use of C, G, V and E were 2nd, 3rd, 3rd, and 4th, respectively. The median duration of treatment was approximately 2 months with C, G, and E compared to 1.6 months with V. Using eribulin as the reference and adjusting for line of therapy and associated prognostic factors, the propensity score weighted Cox regression analysis did not identify statistically significant differences in TTF: C vs. E: HR = 1.15 (0.75 to 1.76), G vs. E: HR = 0.62 (0.34 to 1.13), V vs. E: HR = 1.0 (0.60 to 1.37). Conclusions: In patients with TN-MBC treated in a community oncology setting, eribulin was utilized in later lines than other agents. However, eribulin demonstrated at least comparable drug activity even when used in more heavily pretreated patients. These findings warrant further analyses in a larger population with an evaluation of biologic heterogeneity.

scholarly journals Phase II study of pembrolizumab and capecitabine for triple negative and hormone receptor-positive, HER2−negative endocrine-refractory metastatic breast cancer

2020 ◽  
Vol 8 (1) ◽  
pp. e000173 ◽  
Author(s):  
Ami N Shah ◽  
Lisa Flaum ◽  
Irene Helenowski ◽  
Cesar A Santa-Maria ◽  
Sarika Jain ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Phase Ii Study ◽  
Single Agent ◽  
Metastatic Breast ◽  
Low Grade ◽  
Hormone Receptor Positive

BackgroundResponse rates to single agent immune checkpoint blockade in unselected pretreated HER2−negative metastatic breast cancer (MBC) are low. However, they may be augmented when combined with chemotherapy.MethodsWe conducted a single-arm, phase II study of patients with triple negative (TN) or hormone receptor-positive endocrine-refractory (HR+) MBC who were candidates for capecitabine. Patients were treated with pembrolizumab 200 mg intravenously day 1 and capecitabine 1000 mg/m2by mouth twice daily on days 1–14 of a 21-day cycle. The primary end point was median progression-free survival (mPFS) compared with historic controls and secondary end points were overall response rate (ORR), safety and tolerability. The study had 80% power to detect a 2-month improvement in mPFS with the addition of pembrolizumab over historic controls treated with capecitabine alone.ResultsThirty patients, 16 TN and 14 HR+ MBC, were enrolled from 2017 to 2018. Patients had a median age of 51 years and received a median of 1 (range 0–6) prior lines of therapy for MBC. Of 29 evaluable patients, the mPFS was 4.0 (95% CI 2.0 to 6.4) months and was not significantly longer than historic controls of 3 months. The median overall survival was 15.4 (95% CI 8.2 to 20.3) months. The ORR was 14% (n=4), stable disease (SD) was 41% (n=12) and clinical benefit rate (CBR=partial response+SD>6 months) was 28% (n=8). The ORR and CBR were not significantly different between disease subtypes (ORR 13% and 14%, CBR 25% and 29% for TN and HR+, respectively). The 1-year PFS rate was 20.7% and three patients have ongoing responses. The most common adverse events were low grade and consistent with those seen in MBC patients receiving capecitabine, including hand-foot syndrome, gastrointestinal symptoms, fatigue and cytopenias. Toxicities at least possibly from pembrolizumab included grade 3 or 4 liver test abnormalities (7%), rash (7%) and diarrhea (3%), as well as grade 5 hepatic failure in a patient with liver metastases.ConclusionsCompared with historical controls, pembrolizumab with capecitabine did not improve PFS in this biomarker unselected, pretreated cohort. However, some patients had prolonged disease control.Trial registration numberNCT03044730.

First-in-human phase I/Ib multicenter, open-label dose escalation study to assess safety and tolerability of PMD-026 in patients with metastatic breast cancer with expansion in metastatic triple negative breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS1110-TPS1110
Author(s):  
Muralidhar Beeram ◽  
Judy Sing-Zan Wang ◽  
Lida A. Mina ◽  
Amita Patnaik ◽  
Mary Rose Pambid ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Triple Negative Breast Cancer ◽  
Dose Escalation ◽  
Triple Negative ◽  
Single Agent ◽  
Metastatic Breast ◽  
Open Label

TPS1110 Background: Metastatic triple negative breast cancer (mTNBC) has a poor prognosis with limited durable treatment options. RSK (P90 ribosomal S6 kinase) is a signaling protein at the convergence point of PDK-1 and MAPK signaling pathways. RSK1-3 phosphorylates transcription factors, including Y-box binding protein-1 (YB-1), thereby inducing drug resistance and cancer growth genes. Phosphorylated YB-1 is involved in tumor cell survival, proliferation, and drug resistance. In human breast tumor samples, RSK2 protein is expressed across all breast cancer subtypes (TNBC, ER+ and HER2+) and is associated with poor overall survival. Expression of RSK2 is found in approximately 87% of mTNBC tumors and of those tumors approximately 41% have very high expression of RSK2. PMD-026 is a potent, oral, small molecule RSK inhibitor with high selectivity for RSK2. Preclinical in vivo studies have demonstrated activity both as a single agent and in combination with standard of care therapies. Further, a CAP/CLIA certified IHC method has been developed with Roche to determine tumor expression of RSK2. Methods: This single-arm, open-label, first-in-human, phase I/Ib study evaluates the safety and efficacy of single agent PMD-026 in patients with metastatic breast cancer for whom standard therapies are no longer effective. During dose escalation, the study utilizes an accelerated titration design with single patient cohorts until the occurrence of DLT or Grade 2+ toxicity; then reverts to 3+3 design to define the maximally tolerated dose (MTD) and recommended phase II dose (RP2D). The dose expansion portion will enroll approximately 20 patients with mTNBC. Patients are dosed orally once daily in 21-day cycles with measures to adapt the dosing schedule based on the pharmacokinetic (PK) data, as needed. Tumor tissue is required for all enrolled patients; RSK2 expression will be retrospectively correlated with clinical outcomes. The primary objectives are to determine safety and tolerability of PMD-026, determine the MTD, define a RP2D, and assess anti-tumor activity of PMD-026 in patients with TNBC. Secondary objectives are to evaluate PK, time to response, mTNBC subtyping using NanoString, and duration of response of PMD-026. To date, cohorts 1 and 2 have been completed without DLT. Enrollment to cohort 3 began in January 2020. Clinical trial information: NCT04115306 .

Phase II study of irinotecan plus capecitabine in patients with anthracycline and taxane pretreated metastatic breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1093-1093
Author(s):  
K. S. Lee ◽  
J. Ro ◽  
I. H. Park ◽  
E. A. Kim ◽  
B. Nam
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Triple Negative ◽  
Single Agent ◽  
Objective Response ◽  
Metastatic Breast ◽  
Stage Iv ◽  
Phase Iii ◽  
Cross Resistance ◽  
Median Response

1093 Background: Irinotecan (I) and capecitabine (X) have demonstrated single agent activity against breast cancer by different antitumor mechanism without cross-resistance. To assess the objective response rate (RR) of IX combination in metastatic breast cancer (MBC) patients (pts) was the primary end point. Methods: Anthracycline- and taxane-pretreated pts with measurable disease, age ≥ 18 years, adequate organ functions, and ECOG performance score (PS) 0–2 were eligible. Sample size of 36 was calculated with Simon's two stage minimax design. Pts received I 80 mg/m2 intravenously on days 1 and 8 and X 1,000 mg/m2 orally twice daily on days 1–14 of every 21-day cycle. Results: Between September 2006 and April 2008, 36 pts with median age of 50 years (range, 28–71) were enrolled. Median follow-up was 17 months (range, 8.3+ - 27.7+). Among 35 evaluable pts excluding 1-consent withdrawal, 86% received at least one prior chemotherapy for MBC; 20% had stage IV disease with 66% lung/37% liver metastases; 80% had PS 0–1; 77% had hormone receptor (HR) positive tumors, 20% triple negative disease and 3% HER-2 positive tumors. Overall RR was 60% (95% CI, 43.5–74.5) with median response duration of 6.3 months (range, 1.0+-17.1+); 2 CR (6%), 19 PR (54%), 8 SD (23%), and 6 PD (17%) with similar RR between HR+ (63%) versus triple negative disease (57%). Median survival was not reached with 76% estimated survival at 1-year, and median progression free survival (PFS) was 7.3 months (range, 0.7–21.1+). Pts received a median of 8 cycles of treatment (range, 1–26+). G1, G2, and G3 hand-foot syndrome were observed in 34%, 17%, and 0%, respectively. NCI grade ≥ 3 adverse events were: neutropenia (60%); asthenia, diarrhea, and vomiting (9%, each); transaminase elevation and febrile neutropenia (6%, each); abdominal pain, anorexia, fatigue, myalgia, and nausea (3%, each). Conclusions: I and X combination by this schedule and doses is highly efficacious in anthracyline- and taxane-pretreated MBC pts with manageable toxicities. Further investigation of this combination in phase III trials is warranted. No significant financial relationships to disclose.

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