CONTESSA: A multinational, multicenter, randomized, phase III registration study of tesetaxel plus a reduced dose of capecitabine in patients (pts) with HER2-, hormone receptor + (HR+) locally advanced or metastatic breast cancer (LA/MBC) who have previously received a taxane.
Joyce O’ShaughnessyMartine PiccartLee S. SchwartzbergJavier CortésNadia HarbeckSeock‐Ah ImHope S. RugoMichael UntchDenise A. YardleyIgor BondarenkoStephen ChanVéronique DièrasMark D. PegramStew KrollJoseph O’ConnellJeff VacircaThomas WeiKevin TangAndrew D. Seidman
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TPS1107 Background: Chemotherapy treatments with robust efficacy that preserve quality of life are needed. Tesetaxel (T) is a novel, oral taxane that has potential advantages over currently available taxanes, including: oral administration with a low pill burden and Q3W dosing regimen; no observed hypersensitivity reactions; preclinical evidence of CNS penetration; and improved activity against chemotherapy-resistant tumors. Over 600 pts have been treated with T in clinical studies. T had robust monotherapy activity in a Phase 2 study in 38 pts with HER2-, HR+ MBC who received T Q3W, with a confirmed ORR per RECIST 1.1 of 45% and median PFS of 5.4 mo. The confirmed ORR in taxane-pretreated pts was 45%. Preclinical and clinical studies suggest that reducing the dose of capecitabine (C) in combination with a taxane may result in reduced toxicity without reduction in efficacy. Preclinical data also suggest that T may penetrate the brain at clinically relevant concentrations. CONTESSA investigates T plus a reduced dose of C as an all-oral regimen in HER2-, HR+ LA/MBC, with revised eligibility criteria to allow inclusion of pts with CNS metastases. Methods: CONTESSA is a 600-pt, multinational, multicenter, randomized (1:1), Phase 3 registration study comparing T (27 mg/m 2 on Day 1 of a 21-day cycle) plus a reduced dose of C (1,650 mg/m 2 /day on Days 1-14 of a 21-day cycle) to the approved dose of C alone (2,500 mg/m 2 /day on Days 1-14 of a 21-day cycle) in pts with HER2-, HR+ LA/MBC previously treated with a taxane in the (neo)adjuvant setting. The protocol was newly amended to allow pts with known CNS metastases. The primary endpoint is PFS assessed by an Independent Radiologic Review Committee (IRC). CONTESSA is 90% powered to detect a 42% improvement in PFS (HR = 0.71). Secondary endpoints are OS, ORR, and disease control rate. Enrollment began in Dec 2017. Following review in Jan 2019, the Independent Data Monitoring Committee recommended that the Study continue as planned. Clinical trial information: NCT03326674.Keywords:
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There is little information available on the patterns of chemotherapy regimens administered in daily practice to patients with early stage and metastatic or recurrent breast cancer. To determine the trends in type of chemotherapy regimens used in breast cancer patients, newly diagnosed breast cancer patients in the period 2000–2008 who received chemotherapy were identified from the Eindhoven Cancer Registry (ECR) and linked to the PHARMO RLS, including data on, e.g., in- and outpatient drug use. Chemotherapy regimens were classified based on the received combinations and sequences. Trends in the distribution of adjuvant chemotherapy regimens (for early-stage breast cancer) and palliative chemotherapy regimens (for metastatic or recurrent breast cancer) were determined and stratified by Her2/neu status when possible. In this study, 422 patients diagnosed with early-stage breast cancer received adjuvant chemotherapy. The use of CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) decreased from 90% in 2000 to almost none since 2005. Administration of regimens that included anthracyclines increased from 4% in 2000 to 96% in 2005, but decreased to 68% in 2008. The use of trastuzumab- and taxane-containing regimens (with or without anthracyclines) increased from 2005 onwards to 24% and 34%, respectively, in 2008. Among the 82 breast cancer patients who received palliative chemotherapy at diagnosis or after breast cancer recurrence, the use of CMF and anthracyclines (without taxanes) decreased, while the use of taxanes (with or without anthracyclines) increased (26% in 2008). Trastuzumab was used as palliative chemotherapy from 2003 onwards, with 22% of the metastatic breast cancer patients receiving trastuzumab-containing regimens in 2008, and bevacizumab was administered since 2007 with 19% of the patients receiving bevacizumab-containing regimens in 2008. In conclusion, major changes have taken place in the chemotherapeutic treatment of patients with early and recurrent breast cancer. These changes reflect the key findings from large clinical trials, as incorporated in the Dutch guidelines.
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Objective To investigate the effect of PR expression on the sensitivity of chemotherapy with TC regimen in locally advanced breast cancer patients.Methods The expression of PR was detected by EnVision immunohistochemistry in breast cancer tissues before neoadjuvant chemotherapy with TC regimen in corresponding patients,and the correlation of PR expression with the sensitivity of chemotherapy were studied in 57 PR negative or positive patients.Results The sensitivity was 81.48%(22/27)in PR negative breast tumours,and was 53.33%(16/30) in PR positive breast tumours with TC regimen in locally advanced breast cancer patients,and there was significant difference of sensitivity between breast cancer patients with PR negative and positive tumours(P0.05).Conclusion PR negative breast cancer patients were more sensitive to neoadjuvant chemotherapy.PR negative may serve as one of good markers for prediction of sensitivity of neoadjuvant chemotherapy with TC regimen in locally advanced breast cancer patients.
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Taxanes belong to the most effective agents in the treatment of advanced and non-hormone responsive breast cancer. Several recently published phase III studies have examined the role of taxane-anthracycline combinations in the first line treatment of metastatic breast cancer. Especially, patients with symptomatic visceral spread seem to benefit from taxanes containing polychemotherapy that is adequately dosed. Polychemotherapy with taxanes appears to be more effective than monotherapy. But at present, there are no adequate data concerning the comparison of taxane-monotherapy and anthracycline-containing polychemotherapy. New hopeful results with respect to efficacy and toxicity are reported from the docetaxel-capecitabine polychemotherapy. Thus, the combination of anthracyclines (adriamycin, doxorubicin) and taxanes (docetaxel, paclitaxel) is a promising tool in the treatment of metastatic breast cancer. New interesting combinations are under investigation.
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OBJECTIVE: To observe the efficacy and toxicity of capecitabine combination with gemcitabinein on anthracycline-and-taxane-resistant metastatic breast cancer.METHODS: 30 patients of anthracycline-and-taxane-resistant metastatic breast cancer were treated with capecitabine and gemcitabinein combination regimen.Capecitabine was orally given at a dose of 2 000 mg/(m2·d),two weeks;gemcitabinein was given at a dose of 1 000 mg/m2 by intravenous infection at day 1 and day 8,21 days apart for each cycle,at least two cycles were given.RESULTS: The ORR was 53.3% including CR 3 cases,PR 13 cases,SD 9 cases and PD 5 cases.The MST was 14 months,the one-year survival rate was 56.7%;The main toxicity was myelosuppression,nausea and vomitimg,hand-foot syndrome.CONCLUSION: Capecitabine and gemcitabinein combination regimen has good anti-tumor activity and good toleration on patients with anthracycline-and-taxane-resistant metastatic breast cancer.
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e12035 Background: Capecitabine is a potent and safe agent, which can be used after antracycline and taxane treatment in patients with metastatic breast cancer (MBC). The purpose of this study was to investigate the efficacy and safety of capecitabine monotherapy as a first-line treatment in HER-2 negative MBC patients. Methods: In this single center trial, a total of 109 HER-2 negative MBC patients who received capecitabine monotherapy in the first-line treatment between 2003 and 2014 were retrospectively analyzed.Kaplan Meier survival analysis was carried out for progression free survival (PFS) and for overall survival (OS). Two-sided p values of < 0.05 were considered as statistically significant. Results: Median PFS was 7.0 ±0.67 (CI: 5.6-8.3) months and median OS was 30 ±4.1 (CI: 21.8-38.1) months. First-line capecitabine treatment for HER-2 negative MBC was more effective in ER positive patient population compared to ER negative group (median PFS: 9 vs. 4 months (p = 0.002), median OS: 33 vs. 21 months (p = 0.01). Indeed, the overall response rate in ER negative group was 16%, while this was calculated as 38% for ER positive cases. While most of our patient population was treated with a higher dose (1250 mg/m2), the observed grade 3-4 toxicities were lower compared to some previously reported phase II and phase III capecitabine studies. Conclusions: Capecitabine monotherapy is an effective and safe regimen for ER positive, HER-2 negative MBC patients. Its low toxicity profile compared to other intravenous cytotoxic agents and the ease of its oral administration make this agent a preferable option for both physicians and patients.
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Objective To observe the near futur effect of gemcitabine and capecitabine regimen treatment of patients with metastatic breast cancer.Methods 27patients with metastatic breast cancer were evaluated in gemcitabine and capecitabine regimen.Results 1 patient were CR,18 patients were PR,5 patients was NC,3patients were PD,total remission rate was 70.4%.The most effect was hand-foot syndrome,leukocytopenia.Conclusion This regimen shows more better for metastatic breast cancer,its toxic reaction are tolerable.
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261 Background: Over 155,000 women are living with metastatic breast cancer (mBC) in the US. Chemotherapies can prolong survival for women with mBC, but adverse events (AEs) stemming from their use are common and costly to manage. We compared the healthcare costs for taxane- (TAX) and capecitabine-based (CAP) treatments for mBCpatients as either first- or second-line (FL or SL) therapy in the US. Methods: Using the Marketscan Commercial Database, a nationally representative database of over 52 million people, we selected mBC patients diagnosed from 2008-2011. Patients were categorized into FL and SL chemotherapy including either a TAX (paclitaxel or docetaxel) or CAP using an algorithm based on pharmacy and medical claims data. Chemotherapy-related AEs were identified by ICD-9 codes. Costs were tabulated from a payer perspective. Average monthly costs were stratified by treatment and the presence/absence of AEs. Results: Among 15,535 mBCpatients we identified 15,472 FL and 6,809 SL cases treated with TAX or CAP. The mean age of patients was 51 years (SD 8). At least one AE was experienced during FL treatment by 74% (SD 44%) and 68% (SD 46%) of TAX and CAP users and during SL treatment 60% (SD 49%) and 59% (SD 49%), respectively. Average monthly total costs during the FL period were $2,385 higher (p <0.0001) and $1,679 higher (p=0.28) for TAX- and CAP-treated patients who experienced at least one AE. In SL, costs for patients with at least one AE had were $2,995 (p<0.0001) higher for TAX-treated patients and $4,870 (p=0.0026) higher for CAP-treated patients. Conclusions: Among community-treated patients, AEs are common in women with mBC receiving TAX- and CAP-based chemotherapy regimens. These AEs are associated with higher costs in FL and SL. When possible, prevention or earlier management of AEs may represent an opportunity to reduce costs and improve outcomes for women with mBC. [Table: see text]
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