Bevacizumab and pegylated liposomal doxorubicin as first-line therapy for locally recurrent or metastatic breast cancer: A multicenter, single-arm phase II trial of the Swiss Group for Clinical Cancer Research (SAKK)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1030-1030
Author(s):  
C. Rochlitz ◽  
C. Spirig ◽  
T. Ruhstaller ◽  
T. Suter ◽  
M. Bühlmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Liposomal Doxorubicin ◽  
Cardiac Toxicity ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Advanced Breast ◽  
First Line ◽  
Hand Foot Syndrome ◽  
Grade 3

1030 Background: Bevacizumab in combination with taxanes has become a standard first-line treatment of advanced breast cancer in some countries, but there is no information on its use in combination with pegylated lipsomal doxorubicin in metastatic breast cancer. Therefore, we performed a multicenter, single-arm phase II trial to evaluate the toxicity and efficacy of pegylated liposomal doxorubicin (PLD) and bevacizumab (B) as first-line treatment in advanced breast cancer. Methods: PLD at a dose of 20 mg/m2 and B at 10 mg/kg were infused on days 1 and 15 of each 4-week cycle for a maximum of 6 cycles. Thereafter, B monotherapy was continued at the same dose until progression or toxicity. Primary endpoint was the occurrence of specific toxic events known to strongly interfere with quality of life, i.e., severe cardiac toxicity, any grade 4/5 toxicity, and selected grade 3 nonhematological toxicities (hand-foot-syndrome, cognitive disturbance, CNS hemorrhage, and mucositis/stomatitis). Secondary endpoints included overall response, progression free survival (PFS), time to treatment failure, and duration of response. Eligibility criteria included documentation of metastatic or inoperable breast cancer; measurable disease according to RECIST; erbB2-negativity; LVEF of ≥ 55%; WHO performance status 0 or 1. The study used a Herndon's two-stage design with 14 and 29 patients for stages 1 and 2, respectively. The promising rate of primary toxicity was <15% and the uninteresting rate >33%. The type I error probability was 5% and the power 80%. Results: The trial had to be stopped prematurely because of toxicity after the enrollment of 41 evaluable patients. Among these patients, 16 (39%) had grade 3 hand-foot syndrome, 1 grade 3 mucositis and 1 grade 4 cardiac toxicity. Thus, a total of 18/41 (44%, exact 95% c.i. 28–60%) of all patients had a primary toxicity. Best overall response rate was 23.3% (exact 95% c.i. 12–39%), median PFS was 7.5 months (95% c.i. 4.6–8.1 months). Conclusions: The combination of 2-weekly PLD and B in advanced breast cancer is surprisingly toxic and only modestly active and should not be further investigated. [Table: see text]

Phase II trial of pegylated liposomal doxorubicin-cyclophosphamide combination as first-line chemotherapy in elderly metastatic breast cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19565-19565 ◽  
Author(s):  
P. R. Dufour ◽  
F. Rousseau ◽  
N. Meyer ◽  
T. Delozier ◽  
D. Serin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Liposomal Doxorubicin ◽  
Phase Ii Trial ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
First Line ◽  
Grade 3 ◽  
Line Chemotherapy

19565 Background: Although the majority of metastatic breast cancer (MBC) patients (pts) responds to endocrine therapy, treatment failure is a concern, as well as front-line therapy for pts with ER/PR negative disease.The combination of anthracyclines (A) and cyclophosphamide (C) is active in younger pts, but cardiac toxicity of A in elderly MBC pts has to be considered. Pegylated liposomal doxorubicin (PLD) (Caelyx®) is active in MBC and has much less cardiotoxicity than A, and we present the preliminary data of the PLD/C in elderly MBC pts. Methods: This was a multicentric phase II trial. Inclusion criteria included: pts aged between 65 and 75, histologically proven measurable MBC, ECOG PS 0–1, LVEF = 50%, first-line chemotherapy for MBC. Prior adjuvant chemotherapy was allowed if stopped for = 6 or 12 months without and with anthracyclines, respectively. Endocrine therapy either in the adjuvant or metastatic setting had to be stopped for = 1 month. All pts gave a written informed consent. The treatment schedule was : PLD 40mg/m2 and C 500mg/m2 d1 every 4 weeks. Efficacy as well as response duration and tolerance were the primary and secondary end-points, respectively. Results: 35 patients were enrolled (Median age 71.3, range 65.6–75.9). A total of 166 cycles have been administered. The median number of cycles was 6 (range 1–9). No toxic death was reported, one patient died of diabetes mellitus decompensation. No congestive heart failure or decrease in LVEF was reported, although 1 pt experience grade 3 dyspnea and stopped treatment. Other (gr3–4) NCI-CTC toxicity included: neutropenia in 7 (gr3) and 3 (gr4) pts; gr3 mucositis (4). No febrile neutropenia was reported. Grade 3 hand-foot syndrome occurred in 1 pt, whereas treatment was stopped due to a generalized rash in 1 pt. An objective response (CR + PR) was achieved in 10 (28,6%) pts (1 CR and 8 PR), and a disease control in 24 (68.6%) with a progression free survival of 8.8 months and a median survival of 20.4 months Conclusions: The LPD-C combination is active in elderly MBC pts, with an acceptable toxicity profile. No significant financial relationships to disclose.

Pegylated liposomal doxorubicin in combination with gemcitabine in elderly women with locally advanced or metastatic breast cancer: Safety and activity results of our clinical experience

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e12005-e12005
Author(s):  
B. Adamo ◽  
T. Franchina ◽  
N. Denaro ◽  
C. Garipoli ◽  
G. Ferraro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Clinical Benefit ◽  
Liposomal Doxorubicin ◽  
Elderly Women ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Advanced Breast ◽  
Left Ventricular Ejection ◽  
Grade 3

e12005 Background: Elderly breast cancer patients have an increased risk of toxicity from chemotherapy, especially from anthracycline-based regimens. Pegylated liposomal doxorubicin (PLD) has shown a better tolerability profile also in combination with gemcitabine (GEM), as evidenced in several phase II trials. The aim of this study is to retrospectively evaluate the safety and activity of this combination in chemo-naïve or pre-treated elderly patients with advanced breast cancer. Methods: From January 2006 to March 2008, 39 patients (pts) with age ≥ 65 received, at our institution, PLD 25 mg/m2 (day 1, q21) and GEM 800 mg/m2 (days 1 and 8, q21). Median age was 72 (range, 65–79). ECOG PS was 0/1/2 in 14/23/2 pts, respectively. 12 pts (31%) were chemo-naïve, 20 (51%) received prior adjuvant anthracycline-based regimens, and 7 (18%) received other chemotherapies. PLD-GEM combination was administered as first line in 35 pts (90%). Median left ventricular ejection fraction (LVEF) at baseline was 61% (range, 50%-75%). 28 patients (72%) had metastatic disease: 10 in liver, 6 in lung, 2 in skin, and 10 in multiple sites. Estrogen receptor was positive in 32 pts (82%); HER-2+ in 5 pts; 7 pts were triple negative. Results: A total of 206 cycles were administered with a mean number of cycles per patient of 5.2 (range, 3–12). Grade 3–4 neutropenia occurred in 4 (10%) and 3 patients (8%), respectively; grade 3 anemia in two pts (5%). Non-hematological toxicity was mild, with 5 cases (13%) of grade 3 mucositis, and 2 cases (5%) of grade 2 palmar-plantar erythrodysesthesia syndrome. No modifications in LVEF or toxic deaths were documented. We observed 1 CR (2.5%) and 11 PR (28.2%). Eighteen (44%) patients experienced SD for 16 weeks and an overall clinical benefit of 76.8%. Conclusions: The combination of PLD and GEM has a favorable tolerability and a safety profile with an evident clinical benefit and should represent an interesting treatment option in elderly women with advanced breast cancer. No significant financial relationships to disclose.

Randomized Phase III Trial of Pegylated Liposomal Doxorubicin Versus Vinorelbine or Mitomycin C Plus Vinblastine in Women With Taxane-Refractory Advanced Breast Cancer

2004 ◽  
Vol 22 (19) ◽  
pp. 3893-3901 ◽  
Author(s):  
Alan M. Keller ◽  
Robert G. Mennel ◽  
Vassilis A. Georgoulias ◽  
Jean-Marc Nabholtz ◽  
Aura Erazo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Mitomycin C ◽  
Metastatic Disease ◽  
Liposomal Doxorubicin ◽  
Therapeutic Option ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Advanced Breast ◽  
Phase Iii

Purpose To compare the efficacy of pegylated liposomal doxorubicin (PLD) with that of a common salvage regimen (comparator) in patients with taxane-refractory advanced breast cancer. Patients and Methods Following failure of a first- or second-line taxane-containing regimen for metastatic disease, 301 women were randomly assigned to receive PLD (50 mg/m2 every 28 days); or comparator-vinorelbine (30 mg/m2 weekly) or mitomycin C (10 mg/m2 day 1 and every 28 days) plus vinblastine (5 mg/m2 day 1, day 14, day 28, and day 42) every 6 to 8 weeks. Patients were stratified before random assignment based on number of previous chemotherapy regimens for metastatic disease and presence of bone metastases only. Results Progression-free survival (PFS) and overall survival (OS) were similar for PLD and comparator (PFS: hazard ratio [HR], 1.26; 95% CI, 0.98 to 1.62; P = .11; median, 2.9 months [PLD] and 2.5 months [comparator]; OS: HR, 1.05; 95% CI, 0.82 to 1.33; P = .71; median, 11.0 months [PLD] and 9.0 months [comparator]). In anthracycline-naïve patients, PFS was somewhat longer with PLD, relative to the comparator (n = 44; median PFS, 5.8 v 2.1 months; HR, 2.40; 95% CI, 1.16 to 4.95; P = .01). Most frequently reported adverse events were nausea (23% to 31%), vomiting (17% to 20%), and fatigue (9% to 20%) and were similar among treatment groups. PLD-treated patients experienced more palmar-plantar erythrodysesthesia (37%; 18% grade 3, 1 patient grade 4) and stomatitis (22%; 5% grades 3/4). Neuropathy (11%), constipation (16%), and neutropenia (14%) were more common with vinorelbine. Alopecia was low in both the PLD and vinorelbine groups (3% and 5%). Conclusion PLD has efficacy comparable to that of common salvage regimens in patients with taxane-refractory metastatic breast cancer, thereby representing a useful therapeutic option.

Pilot study with pegylated liposomal doxorubicin (PLD) and docetaxel as first-line treatment in patients with metastatic breast cancer (MBC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e12002-e12002
Author(s):  
J. R. Mel ◽  
M. Ramos ◽  
J. Cueva ◽  
J. Castellanos ◽  
C. Almanza
Keyword(s):  
Breast Cancer ◽  
Liposomal Doxorubicin ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Dose Intensity ◽  
Cytotoxic Agents ◽  
Line Treatment ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

e12002 Background: Anthracyclines (AC) and taxanes are the most active cytotoxic agents for the treatment of MBC. The use of AC is limited by their acute toxicities and by their potential to cause cumulative cardiac damage. The development of alternative formulations of AC, such as pegylated liposomal doxorubicin (PLD) with lower toxicity may improve tolerability and efficacy of AC based regimens. This study has been conducted to determine the efficacy and toxicity profiles of docetaxel and PLD as first line treatment in patients (pts) with MBC. Methods: Pts ≥ 18 years with histologically confirmed breast cancer, advanced disease, PS ≥ 60%, LVEF> 50%, adequate bone marrow, renal and hepatic function were included. No prior systemic therapy for MBC was allowed. Pts with brain metastases were excluded. Docetaxel 60 mg/m2 iv followed by PLD 30 mg/m2 iv day 1 every 3 weeks up to 6 cycles were given. Results: Thirty women with a median age of 64 years (40–81) were included. (76.7%) of pts were postmenopausal, Karnofsky PS 100 and 90 were 48% and 21% respectively, 86% of pts had ductal carcinoma. Most common sites of metastasis were lung (57%), liver (47%), and bone (43%). 20/30 (67%) of pts were pretreated, 15 (50%) pts with AC-containing regiment and 17 (57%) with radiotherapy. A total of 157 cycles (median 6, range 2–6) were administered. Median relative dose intensity was 90% for docetaxel and 88% for PLD. Over 28 pts assessable for response, overall response rate was 35.7% (95% CI: 18.0%-53.4%), all of them PR. With a median follow-up of 20.5 months, median time to progression was 8.1 months. Main grade 3 nonhaematological toxicities were PPE (27%), mucositis (27%), and asthenia (17%). No grade 4 nonhaematological toxicities were observed. Main grade 3/4 haematological toxicities were neutropenia (17%), leucopenia (10%), and thrombopenia (6.7%). 4 pts (13%) had febrile neutropenia. Conclusions: Docetaxel and PLD administered every 21 days as first-line treatment in MBC is an active schedule with an acceptable toxicity profile. No significant financial relationships to disclose.

Non-pegylated liposomal doxorubicin and docetaxel as first-line treatment in metastatic breast cancer

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 753-753 ◽  
Author(s):  
V. Heilmann ◽  
H. Eggemann ◽  
H. Sommer ◽  
G. Heinrich ◽  
J.-U. Blohmer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Liposomal Doxorubicin ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA (ctDNA) in metastatic breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1015-1015
Author(s):  
Charlotte Victoria Fribbens ◽  
Isaac Garcia-Murillas ◽  
Matthew Beaney ◽  
Sarah Hrebien ◽  
Karen Howarth ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Advanced Breast Cancer ◽  
Disease Progression ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Plasma Samples ◽  
First Line ◽  
Ras Mutations ◽  
Esr1 Mutations

1015 Background: Selection of resistance mutations may play a major role in the development of endocrine resistance. ESR1 mutations are rare in primary breast cancer but have a high prevalence in patients treated with aromatase inhibitors (AI) for advanced breast cancer. We investigated the evolution of genetic resistance to first line AI therapy using sequential ctDNA sampling in patients with advanced breast cancer. Methods: Seventy-one patients on first line AI therapy for metastatic breast cancer were enrolled in a prospective study to collect plasma samples for ctDNA analysis every three months on therapy, and at disease progression. All plasma samples were analysed with ESR1 multiplex digital PCR assays, and samples at disease progression were analysed by InVision (enhanced tagged-amplicon sequencing). Mutations were tracked back through samples prior to disease progression to study the evolution of mutations on therapy. Results: Of the 34 patients who progressed on first line AI, 53% (18/34) had ESR1 mutations detectable at progression. Sequencing of progression plasma ctDNA identified polyclonal RAS mutations in 10.7% (3/28) progressing patients (2 polyclonal KRAS, 1 monoclonal HRAS), all of whom also had ESR1 mutations, and a patient with an activating p.R248C FGFR3 mutation. ESR1 mutations were subclonal in 78.6% (11/14) patients, with all RAS mutations being rare subclones. In serial tracking prior to progression, ESR1 mutations were detectable in plasma with a median of 5.3 months (95% CI 2.9-NA) prior to clinical progression. Conclusions: ESR1 mutations are found at high frequency in patients progressing on AI, but are frequently sub-clonal and may not be the sole driver of AI resistance in these patients. Poly-clonal KRAS mutations are identified as a novel mechanism of resistance to AI, associated with detection of ESR1 mutations.

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