scholarly journals Eribulin in the Management of Advanced Breast Cancer: Implications of Current Research Findings

2015 ◽  
Vol 9 ◽  
pp. BCBCR.S32787 ◽  
Author(s):  
Victor C. Kok
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Cytotoxic Agents ◽  
European Medicines Agency ◽  
Eribulin Mesylate ◽  
Halichondrin B ◽  
Taiwan National Health Insurance ◽  
Grade 3

The search for cytotoxic agents from marine natural products ultimately led to the production of eribulin, which is a synthetic macrocyclic ketone analog of halichondrin B. Eribulin binds to tubulin to induce mitotic arrest and gained approval in Japan in May 2010; it was approved by the US Food and Drug Administration in November 2010 and the European Medicines Agency in March 2011 and was reimbursed by the Taiwan National Health Insurance in December 2014 for patients with metastatic breast cancer who had received at least one anthracycline and one taxane. The recommended regimen for eribulin mesylate comprises intravenous administration of 1.4 mg/m2 (equivalent to 1.23 mg/m2 eribulin) over two to five minutes on days 1 and 8 of a three-week cycle. Since 2011, various clinical investigations of eribulin monotherapy with dose or schedule modifications, combined use with other antineoplastic therapeutics, or head-to-head comparisons with specific agents have been performed in the management of advanced breast cancer. Ethnic-specific data from Japan and Korea indicate higher rates (>85%) of grade 3 or 4 neutropenia. Some anecdotal evidence suggests that eribulin can shrink brain and retinal metastases, which warrants further detailed studies. In this review, current observations of the effects of eribulin monotherapy are summarized and eribulin-backbone combination (bio-) chemotherapy is investigated.

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]

Gemcitabine Plus Paclitaxel Versus Paclitaxel Monotherapy in Patients With Metastatic Breast Cancer and Prior Anthracycline Treatment

2008 ◽  
Vol 26 (24) ◽  
pp. 3950-3957 ◽  
Author(s):  
Kathy S. Albain ◽  
Shona M. Nag ◽  
German Calderillo-Ruiz ◽  
Johann P. Jordaan ◽  
Antonio C. Llombart ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Response Duration ◽  
Advanced Breast ◽  
Phase Iii ◽  
Pivotal Study ◽  
Reasonable Choice ◽  
Grade 3

Purpose The objective of this phase III global study was to compare the efficacy of gemcitabine plus paclitaxel (GT) versus paclitaxel in patients with advanced breast cancer. It was designed as a pivotal study for the approval of G for a breast cancer treatment indication. Patients and Methods Patients who relapsed after adjuvant anthracyclines were randomly assigned to gemcitabine,1,250 mg/m2 days 1 and 8 plus paclitaxel, 175 mg/m2 on day 1; or, to paclitaxel at same dose on day 1 (both arms administered every 21 days, unblinded). The primary end point was overall survival (OS) and secondary end points were time to progression (TTP), response rate (RR), progression-free survival, response duration, and toxicity. This final OS analysis was planned at 380 deaths. Results A total of 266 patients were randomly assigned to GT and 263 to paclitaxel. Median survival on GT was 18.6 months versus 15.8 months on paclitaxel (log-rank P = . 0489), with an adjusted Cox hazard ratio of 0.78 (95% CI, 0.64 to 0.96; P = .0187). The TTP was longer (6.14 v 3.98 months; log-rank P = .0002) and the RR was better (41.4% v 26.2%; P = .0002) on GT. There was more grade 3 to 4 neutropenia on GT and grade 2 to 4 fatigue and neuropathy were slightly more prevalent on GT. Conclusion This phase III study documents a role for gemcitabine in advanced breast cancer after anthracycline-based adjuvant therapy. The results establish GT as a reasonable choice for women who require cytoreduction with manageable toxicities and validate ongoing testing of GT in the adjuvant setting.

Treatment of advanced breast cancer with sterically stabilized liposomal doxorubicin: results of a multicenter phase II trial.

1997 ◽  
Vol 15 (10) ◽  
pp. 3185-3191 ◽  
Author(s):  
M R Ranson ◽  
J Carmichael ◽  
K O'Byrne ◽  
S Stewart ◽  
D Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Active Agent ◽  
Metastatic Breast ◽  
Skin Toxicity ◽  
Advanced Breast ◽  
Multicenter Phase ◽  
Stage Iv Breast Cancer ◽  
Grade 3

PURPOSE A multicenter phase II study to determine the activity and toxicity of Caelyx (Doxil; Sequus Pharmaceuticals Inc, Menlo Park, CA) in patients with metastatic breast cancer. PATIENTS AND METHODS Seventy-one patients with stage IV breast cancer were treated with Caelyx at doses of 45 to 60 mg/m2 every 3 to 4 weeks for a maximum of six cycles. Twenty-eight patients had received prior chemotherapy with a nonanthracycline regimen. Fifty-two patients had disease at multiple sites. Hepatic and pulmonary disease were the predominant metastatic site in 50 patients. Response was assessable in 64 cases. RESULTS Sixteen patients achieved a partial response and a complete response (overall response rate, 31%; (95% confidence interval, 20% to 43%). Twenty patients (31%) had stable disease on treatment. Neutropenia > or = grade 3 occurred in 10% of cycles (27% of patients) and mucositis > or = grade 3 in 10% of cycles (32% of patients). Significant alopecia was rare and routine prophylactic antiemetics were not required. At doses of 60 mg/m2 every 3 weeks, seven of 13 patients had > or = grade 3 skin toxicity; overall, this toxicity complicated 25% of treatment cycles. The incidence of > or = grade 3 skin toxicity was greatly reduced at doses of 45 mg/m2 every 4 weeks, occurring in five of 32 patients and affecting only 5% of 126 treatment cycles. CONCLUSION Caelyx is an active agent in advanced breast cancer with a safety profile that differs markedly from nonliposomal doxorubicin. A regimen of 45 mg/m2 every 4 weeks was well tolerated in this cohort of women with advanced poor-prognosis breast cancer. The mild myelosuppression seen with this regimen would favor its use in combination chemotherapy.

Phase II Study of the Efficacy and Tolerability of Two Dosing Regimens of the Farnesyl Transferase Inhibitor, R115777, in Advanced Breast Cancer

2003 ◽  
Vol 21 (13) ◽  
pp. 2492-2499 ◽  
Author(s):  
Stephen R.D. Johnston ◽  
Tamas Hickish ◽  
Paul Ellis ◽  
Stephen Houston ◽  
Lloyd Kelland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Hematologic Toxicity ◽  
Farnesyl Transferase ◽  
Farnesyl Transferase Inhibitor ◽  
Grade 3

Purpose: R115777 is an orally active farnesyl transferase inhibitor that specifically blocks farnesylation of proteins involved in growth-factor–dependent cell-signal–transduction pathways. We conducted a phase II study in 76 patients with advanced breast cancer. Patients and Methods: Two cohorts of patients were recruited sequentially. The first cohort (n = 41) received a continuous dosing [CD] regimen of R115777 400 or 300 mg bid. The second cohort (n = 35) received 300 mg bid in a cyclical regimen of 21 days of treatment followed by 7 days of rest (intermittent dosing [ID]). Results: In the CD cohort, four patients (10%) had a partial response (PR) and six patients (15%) had stable disease at ≥ 24 weeks (SD). In the ID cohort, five patients (14%) had a PR and three patients (9%) had prolonged SD. The first six patients in the CD cohort treated at 400 mg bid all developed grade 3 to 4 neutropenia, so the subsequent 35 patients were treated at 300 mg bid. The incidence of hematologic toxicity was significantly lower in the ID than in the CD (300-mg bid) cohort: grade 3 to 4 neutropenia (14% v 43%; P = .016) and grade 3 to 4 thrombocytopenia (3% v 26%; P = .013). One patient in the ID cohort developed grade 2 to 3 neurotoxicity compared with 15 patients in the CD cohort (3% v 37%; P = .0004). Conclusion: The farnesyl transferase inhibitor R115777 has demonstrated clinical activity in patients with metastatic breast cancer, and the ID regimen has a significantly improved therapeutic index compared with the CD regimen.

New cytotoxic agents and schedules for advanced breast cancer

2001 ◽  
Vol 28 (4) ◽  
pp. 344-358 ◽  
Author(s):  
Harold J. Burstein ◽  
Craig A. Bunnell ◽  
Eric P. Winer
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Advanced Breast ◽  
Cytotoxic Agents

Plasma ESR1 Mutations and the Treatment of Estrogen Receptor–Positive Advanced Breast Cancer

2016 ◽  
Vol 34 (25) ◽  
pp. 2961-2968 ◽  
Author(s):  
Charlotte Fribbens ◽  
Ben O’Leary ◽  
Lucy Kilburn ◽  
Sarah Hrebien ◽  
Isaac Garcia-Murillas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Advanced Breast Cancer ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Phase Iii ◽  
Wild Type ◽  
Estrogen Receptor Positive ◽  
Esr1 Mutations ◽  
The Impact

Purpose ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor–positive advanced breast cancer. Materials and Methods In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor–Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction. Results In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001). Conclusion ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required.

scholarly journals Implementation and Feasibility of Electronic Patient-Reported Outcome (ePRO) Data Entry in the PRAEGNANT Real-Time Advanced and Metastatic Breast Cancer Registry

2017 ◽  
Vol 77 (08) ◽  
pp. 870-878 ◽  
Author(s):  
Markus Wallwiener ◽  
Felix Heindl ◽  
Sara Brucker ◽  
Florin-Andrei Taran ◽  
Andreas Hartkopf ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Advanced Breast Cancer ◽  
Cancer Registry ◽  
Data Entry ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Patient Reported ◽  
Trial Staff ◽  
Breast Cancer Registry

Abstract Purpose Patient-reported outcomes (PROs) have been incorporated into clinical trials for many symptoms and medical conditions. A transition from paper-based capture of PROs to electronic PROs (ePROs) has recently started. This study reports on the feasibility of ePRO assessment in a prospective registry including molecular data for patients with advanced breast cancer. Methods As part of the PRAEGNANT network, patients were invited by clinical trial staff, physicians, and nurses to complete three standardized Internet-based questionnaires (EQ 5D 5 L, CES-D and IPAQ). Feasibility was assessed by the staff members who assigned the user accounts by the patients. The completeness of the questionnaires was also assessed. Results Fifteen of 17 patients who were asked agreed to participate to complete the PRO questionnaires (EQ-5D-5L and CES-D). However, the IPAQ (physical activity) questionnaire was only validly completed by 9 patients. Feasibility was ranked better by the physicians and dedicated clinical trial staff than by the nursing staff. Conclusions Incorporating ePRO questionnaires into an advanced breast cancer registry is feasible, and no major hurdles were reported. Involving stakeholders from the start, the application is tailored to the capacities and abilities of both patients and clinical staff. The patientsʼ compliance was better with some questionnaires, but others may present difficulties.

PALOMAGE, a French real-world cohort of elderly women beyond age 70 with advanced breast cancer receiving palbociclib: Baseline characteristics and safety evaluation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1012-1012
Author(s):  
Philippe Caillet ◽  
Marina Pulido ◽  
Etienne Brain ◽  
Claire Falandry ◽  
Isabelle Desmoulins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Real World ◽  
Older Patients ◽  
Systemic Treatment ◽  
Safety Data ◽  
Real Life ◽  
Advanced Breast ◽  
Baseline Characteristics ◽  
Grade 3

1012 Background: Advanced breast cancer (ABC) is common in older patients, resulting from the high incidence of breast cancer beyond age 70. This population is often limited in clinical trials. Endocrine therapy (ET) combined with a CDK4/6 inhibitor is the standard of care in ABC overexpressing hormonal receptors (HR+). Data specific to older patients are scarce in the literature, deserving further research. Methods: PALOMAGE is an ongoing French prospective study evaluating palbociclib (PAL) + ET in real life setting in women aged ≥70 with HR+ HER2- ABC, split in 2 cohorts: ET sensitive patients with no prior systemic treatment for ABC (cohort A), and ET resistant patients and/or with prior systemic treatment for ABC (cohort B). Data collected include clinical characteristics, quality of life (EORTC QLQ-C30 and ELD14) and geriatric description [G8 and Geriatric-COre DatasEt (G-CODE)]. This analysis reports on baseline characteristics and safety data for the whole population. Results: From 10/2018 to 10/2020, 400 and 407 patients were included in cohort A and B, respectively. The median age was 79 years (69-98), 15.1% with an age > 85. ECOG performance status (PS) was ≥2 in 17.9% patients, 68.3% had a G8 score ≤14 suggesting frailty, 32.1% had bone only metastasis, and 44% had visceral disease. 35.8% of patients in cohort B had no prior treatment for ABC. Safety data were available for 787 patients. The median follow-up was 6.7 months (IC95% = 6.1-7.6). At start of treatment, full dose of PAL (125 mg) was used in 76% of the patients: 62.6%, 68.7% and 71.6% of patients aged ≥ 80, those with ECOG PS ≥2 and those with a G8 score ≤14, respectively. In the safety population, 70% had ≥1 adverse event (AE), including 43.1% grade 3/4 AE, and 22.9% ≥ 1 serious AE. Most frequent AE reported were neutropenia (43.2%), anemia (17.5%), asthenia (16.3%) and thrombocytopenia (13.6%). Grade 3/4 neutropenia was observed in 32.3% of patients, with febrile neutropenia in 1.1%. Grade 3/4 AE PAL-related were reported in 40.1%, 31.4% of patients aged < 80, ≥80, respectively. Regarding PAL, 23.4% of patients had a dose reduction and 41.8% had a temporary or permanent discontinuation due to AE. Safety data were similar in both cohorts. Geriatric data and impact on safety will be presented. Conclusions: PALOMAGE is a unique large real-world cohort focusing on older patients treated with PAL in France. These preliminary data do not suggest any new safety signal, matching data derived from PALOMA trials. The occurrence of less grade3/4 AE related to PAL in patients aged 80 and beyond might reflect the 30% decrease of PAL dose upfront. Effectiveness analyses are eagerly awaited. Clinical trial information: EUPAS23012 .

scholarly journals 4th International Consensus Conference on Advanced Breast Cancer (ABC4), Lisbon, November 4, 2017

2018 ◽  
Vol 78 (05) ◽  
pp. 469-480
Author(s):  
Michael Untch ◽  
Rachel Würstlein ◽  
Norbert Marschner ◽  
Diana Lüftner ◽  
Doris Augustin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Practice ◽  
Advanced Breast Cancer ◽  
Metastatic Breast ◽  
Consensus Conference ◽  
Advanced Breast ◽  
Diagnosis And Treatment ◽  
Parp Inhibition ◽  
Molecular Testing ◽  
The World

AbstractThe fourth international advanced breast cancer consensus conference (ABC4) on the diagnosis and treatment of advanced breast cancer (ABC) headed by Professor Fatima Cardoso was once again held in Lisbon on November 2 – 4, 2017. To simplify matters, the abbreviation ABC will be used hereinafter in the text. In clinical practice, the abbreviation corresponds to metastatic breast cancer or locally far-advanced disease. This year the focus was on new developments in the treatment of ABC. Topics discussed included the importance of CDK4/6 inhibition in hormone receptor (HR)-positive ABC, the use of dual antibody blockade to treat HER2-positive ABC, PARP inhibition in triple-negative ABC and the potential therapeutic outcomes. Another major area discussed at the conference was BRCA-associated breast cancer, the treatment of cerebral metastasis, and individualized treatment decisions based on molecular testing (so-called precision medicine). As in previous years, close cooperation with representatives from patient organizations from around the world is an important aspect of the ABC conference. This cooperation was reinforced and expanded at the ABC4 conference. A global alliance was founded at the conclusion of the consensus conference, which aims to promote and coordinate the measures considered necessary by patient advocates worldwide. Because the panel of experts was composed of specialists from all over the world, it was inevitable that the ABC consensus also reflected country-specific features. As in previous years, a team of German breast cancer specialists who closely followed the consensus voting of the ABC panelists in Lisbon and intensively discussed the votes has therefore commented on the consensus in the context of the current German guidelines on the diagnosis and treatment of breast cancer 1, 2 used in clinical practice in Germany. The ABC consensus is based on the votes of the ABC panelists in Lisbon.

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