A phase II, multicenter, randomized trial of eribulin plus gemcitabine (EG) vs. paclitaxel plus gemcitabine (PG) in patients with HER2-negative metastatic breast cancer (MBC) as first-line chemotherapy (KCSG BR13-11, NCT02263495).

1082 Background: PG chemotherapy is one of the preferred chemotherapeutic regimens for patients with MBC. Eribulin mesylate is a non-taxane inhibitor of microtubule dynamics of the halichondrin class. A recent pooled analysis with eribulin showed improved overall survival (OS) in various patient subgroups. Furthermore, eribulin may have rational benefit compared with paclitaxel in terms of neurotoxicity. Methods: This study was a prospective randomized phase 2, open-label, two-arm, multi-center study comparing EG with PG chemotherapy for patients with HER-2 negative MBC as first-line treatment. Histologically confirmed breast cancer patients, at least 19 years of age, with no prior history of chemotherapy for MBC with evaluable lesions were included. Prior hormonal therapy as a treatment of Hormone Receptor (HR)-positive MBC was allowed. This design was hypothesized that EG chemotherapy would not be inferior to PG chemotherapy. The primary endpoint was Progression-Free Survival (PFS). Estimated 6 mo. PFS rate for each arm was 70%. The secondary endpoints were: Time to Treatment Failure (TTF); OS; neuropathic scale; toxicity; clinical benefit rate. Results: A total of 118 patients (median age: 50, 24-66) were enrolled between 2015 and 2016, and were randomly assigned to PG (n = 59) or EG (n = 59) chemotherapy. Mean number of metastatic sites was 3 (1-8). Six month PFS rates for both arms were 72% for EG and 73% for PG arm (p = 0.457). PFS in PG arm tends to be longer than in EG group (median PFS 12.6 for PG vs. 9.6 months for EG) without statistical significance. In addition, there was no significant difference in OS between the two groups (not reached vs. 21.2 months, p = 0.223). The median numbers of chemotherapy cycles of both groups were 8 for EG and 10 for PG (range 2-32). CBRs were 44% for EG and 45% for PG arm. Major toxicities were neutropenia and neurotoxicity. Grade II or more neurotoxicity was more common in PG than in EG group (40% vs.25%). Conclusions: EG chemotherapy showed similar clinical benefit with PG chemotherapy in terms of PFS but, more favorable neurotoxicity than PG chemotherapy. Clinical trial information: NCT02263495.

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Open label, comparative, randomised, multicentre study of trastuzumab given with docetaxel versus sequential single agent therapy with trastuzumab followed by docetaxel as first-line treatment for Her2neu+++ metastatic breast cancer patients

http://isrctn.org/> ◽

10.1186/isrctn13770586 ◽

2012 ◽

Author(s):

J.G.M. Klijn

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Single Agent ◽

Metastatic Breast ◽

Line Treatment ◽

Breast Cancer Patients ◽

First Line ◽

Open Label ◽

Single Agent Therapy ◽

First Line Treatment

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A new immunotherapy schedule in addition to first-line hormone therapy for metastatic breast cancer patients in a state of clinical benefit during hormone therapy

Journal of Molecular Medicine ◽

10.1007/s00109-020-01881-3 ◽

2020 ◽

Vol 98 (3) ◽

pp. 375-382 ◽

Cited By ~ 2

Author(s):

Andrea Nicolini ◽

Giuseppe Rossi ◽

Paola Ferrari ◽

Riccardo Morganti ◽

Angelo Carpi

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Hormone Therapy ◽

Cancer Patients ◽

Clinical Benefit ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

First Line

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Spanish Breast Cancer Research Group (GEICAM)

Breast Cancer Online ◽

10.1017/s1470903106009175 ◽

2006 ◽

Vol 9 (S1) ◽

pp. 172-205

Author(s):

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Adjuvant Treatment ◽

Metastatic Breast ◽

Operable Breast Cancer ◽

Phase Iii ◽

Breast Cancer Patients ◽

First Line ◽

Open Label

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by Spanish Breast Cancer Research Group (GEICAM). Clinical trials include: FAC versus CMF as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group. GEICAM/8701Phase III study of concomitant versus sequential chemohormonotherapy (EC plus tamoxifen) as adjuvant chemotherapy for node-positive postmenopausal women. GEICAM/9401High-dose DICEP chemotherapy versus observation in metastatic breast cancer patients with monotopic disease responding to induction chemotherapy with paclitaxel plus epirubicin. Phase III GEICAM trial. GEICAM/9601Vinorelbine infusion over 96 hours in heavily pre-treated patients with metastatic breast cancer: a cooperative study by the GEICAM group. GEICAM/9702Phase II trial of gemcitabine in combination with vinorelbine in patients with metastatic breast cancer resistant to anthracyclines. GEICAM/9704A phase II trial for evaluation of sequential doxorubicin and docetaxel as first-line treatment in metastatic breast cancer. GEICAM/9801A multicenter phase III randomized trial comparing docetaxel with doxorubicin and cyclophosphamide (TAC) versus 5-fluorouracil with doxorubicin and cyclophosphamide (FAC) as adjuvant treatment of operable breast cancer patients with negative axillary lymph nodes. TARGET 0 / GEICAM/9805A multicenter phase III randomized trial to compare the sequential and the concomitant administration of doxorubicin and docetaxel, as first-line chemotherapy treatment for metastatic breast disease. GEICAM/9903Docetaxel plus gemcitabine administered every other week as first-line treatment for metastatic breast cancer. GEICAM/9904Weekly docetaxel as neo-adjuvant treatment in stage II and III breast cancer. GEICAM/9905A multicenter phase III randomized trial comparing 5-fluorouracil with epirubicin and cyclophosphamide (FEC) versus 5-fluorouracil with epirubicin and cyclophosphamide (FEC) followed by weekly paclitaxel as adjuvant treatment of operable breast cancer patients with positive axillary lymph nodes. GEICAM/9906An open, multicenter randomized phase IV trial for the administration of pamidronate to breast cancer patients with bone metastatic disease. GEICAM/2000-01A randomized phase III treatment to compare the administration of vinorelbine versus vinorelbine plus gemcitabine in patients with metastatic breast cancer previously treated with anthracyclines and taxanes. GEICAM/2000-04Maintenance phase III/IV study for the administration of Caelyx versus no treatment, after induction chemotherapy for metastatic breast cancer disease. GEICAM/2001-01A multicenter, cross-over, randomized trial with exemestane versus anastrozole as first-line hormonal treatment of postmenopausal women with metastatic breast cancer disease and positive hormone receptors. GEICAM/2001-03A multicenter, open-label randomized phase III trial for the administration of zoledronate to patients with advanced breast cancer disease and non-symptomatic bone metastasis. GEICAM/2001-05A multicenter phase II trial to evaluate the administration of gemcitabine with doxorubicin and paclitaxel (GAT) as neo-adjuvant treatment of stage III disease breast cancer patients. GEICAM/2002–01A phase II trial to evaluate the administration of doxorubicin with cyclophosphamide (AC) followed by weekly docetaxel (T) as neo-adjuvant treatment of stage II disease breast cancer patients. GEICAM/2002–03A multicenter, open-label, randomized phase III trial comparing six courses of FAC (fluorouracil, doxorubicin, cyclophosphamide) with four courses of FAC followed by 8-weekly administrations of Taxol in the adjuvant treatment of node-negative patients with operable breast cancer. GEICAM/2003–02A multicenter, open-label, randomized phase III trial comparing epirubicin plus cyclophosphamide (EC) followed by docetaxel (T) with epirubicin plus docetaxel (ET) followed by capecitabine (X) in the adjuvant treatment of node-positive patients with operable breast cancer. GEICAM/2003–10Open-label, no randomized, phases I–II of the treatment with Myocet/Taxotere/Herceptin as primary antineoplasic treatment in newly diagnosed breast cancer patients with HER2neu overexpression. GEICAM/2003–03Phase IV.II clinical trial with the combination of pegylated liposomal doxorubicin, cyclophosphamide and trastuzumab in patients with metastatic breast cancer with overexpression HER2neu. GEICAM/2004–05Randomized clinical trial to compare the benefit of adding trastuzumab to the combination of capecitabine plus vinorelbine as second-line treatment for patients with locally advanced non-operable breast cancer or metastatic breast cancer with overexpression of HER2, who have progressed to a previous line of treatment for metastatic disease that included trastuzumab in combination with taxanes. GEICAM/2004–06Phase IV.II clinical trial, multicenter, for administration of capecitabine concomitant to radiotherapy in patients with locally advanced breast cancer and HER2neu negatives. GEICAM/2005–01Phase IV.III, multicenter, open, randomized treatment study to evaluate the efficacy of maintenance therapy with capecitabine after standard chemotherapy with anthracyclines in patients with metastatic breast cancer. GEICAM/2005–04

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Lack of Benefit of Maintenance Paclitaxel in First-Line Chemotherapy in Metastatic Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.06.1812 ◽

2006 ◽

Vol 24 (24) ◽

pp. 3912-3918 ◽

Cited By ~ 68

Author(s):

Alessandra Gennari ◽

Dino Amadori ◽

Mario De Lena ◽

Oriana Nanni ◽

Paolo Bruzzi ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Combination Chemotherapy ◽

Metastatic Breast ◽

Progression Free Survival ◽

Breast Cancer Patients ◽

First Line ◽

Free Survival ◽

Median Progression Free Survival ◽

Significant Difference

Purpose This randomized study compared maintenance paclitaxel with control in metastatic breast cancer patients not experiencing progression after first-line anthracycline/paclitaxel combination chemotherapy. Methods Between April 1998 and October 2003, 459 metastatic breast cancer patients received first-line combination chemotherapy with epirubicin or doxorubicin plus paclitaxel. Of these, 255 who had a response or stable disease were then randomly assigned onto the Maintenance Paclitaxel 1 (MANTA1) study, comparing eight courses of maintenance paclitaxel versus control (ie, no additional chemotherapy administration). The primary end point was progression-free survival. Results The study was prematurely concluded after a futility analysis, which was performed on 215 of the 238 patients randomly assigned within December 2002. Of these, 109 patients were assigned to maintenance paclitaxel and 106 were assigned to stopping chemotherapy. No significant difference in median progression-free survival was observed (8.0 months for maintenance paclitaxel and 9.0 months for control). There was no significant difference in median survival time (28.0 v 29.0 months). When the Bayesian method for monitoring clinical trials was applied to these data, even under an enthusiastic prior distribution, in the posterior distribution there was only an 8.6% chance of observing a 3-month improvement in median progression-free survival in the group receiving maintenance paclitaxel. After these results study accrual was closed. Conclusion Compared with control, the administration of additional courses of paclitaxel in patients who achieve disease control after six to eight courses of first-line anthracycline plus paclitaxel combination chemotherapy does not improve progression-free survival.

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A phase III, multicenter, randomized trial of maintenance versus observation after achieving clinical response in patients with metastatic breast cancer who received six cycles of gemcitabine plus paclitaxel as first-line chemotherapy (KCSG-BR 0702, NCT00561119).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1003 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 1003-1003

Author(s):

Young-Hyuck Im ◽

Yeon Hee Park ◽

Kyung Hae Jung ◽

Seock-Ah Im ◽

Joo Hyuk Sohn ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Randomized Trial ◽

Statistical Significance ◽

Metastatic Breast ◽

Hazard Ratio ◽

Phase Iii ◽

Maintenance Chemotherapy ◽

First Line ◽

Significant Difference

1003 Background: Chemotherapy provides a survival benefit in patients with metastatic breast cancer (MBC), but the optimal duration of chemotherapy remains controversial. Primary purpose of the study was to evaluate whether the maintenance chemotherapy with gemcitabine/paclitaxel (GP), which is one of the two regimens which showed a survival gain from a randomized trial, is superior to observation in terms of progression free survival (PFS) in responding patients with MBC after 6 cycles of GP as first-line treatment. Methods: This study is a prospective, randomized, multi-center, phase III study. Patients who achieved response (CR+PR+SD) following 6 cycles of GP chemotherapy (gemcitabine 1250 mg/m2 on day 1 and 8 plus paclitaxel 175 mg/m2 on day 1 every 3 weeks) randomized to maintenance till progression or observation arm. The trial was conducted by the Korean Cancer Study Group (KCSG). Results: Among total 324 patients enrolled between 2007 and 2010 from 10 centers, 231 responding patients to were randomly assigned to maintenance chemotherapy (n=116) or observation (n=115). Median age was 49 (range 28-76). The numbers of hormone receptor (HR)+ve and HR-ve patients were 172 (74.5%) and 59 (25.5%), respectively. The median No. of chemotherapy cycles in maintenance group was 12 (range 6-32). During median 33 months of follow-up, median PFS was superior in maintenance than in observation (12.0 vs. 8.3 months, p=0.030). Patients < age 50 years (hazard ratio 0.50, p=0.001) and HR-ve patients (hazard ratio 0.52, p=0.019) received more benefit from maintenance chemotherapy in terms of PFS. Median OS was superior in maintenance than in observation (36.8 vs 28.0 months, p=0.047). Neurotoxicity (≥ grade 2) was more common in maintenance than in observation without statistical significance (41.7% vs 33.3%, p=0.210). Serial assessment of Quality of Life (QoL) did not show any significant difference between two groups. Conclusions: Maintenance GP chemotherapy for responding patients with MBC showed clinical benefit in terms of PFS and OS without impairment of QoL.

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Faculty of 1000 evaluation for Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer: interim efficacy results of the randomised, open-label, non-inferiority, phase 3 TURANDOT trial.

F1000 - Post-publication peer review of the biomedical literature ◽

10.3410/f.717976445.793471388 ◽

2013 ◽

Author(s):

Ana Maria Gonzalez-Angulo

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Line Treatment ◽

First Line ◽

Open Label ◽

Phase 3 ◽

First Line Treatment

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Phase II study of metronomic treatment with daily oral vinorelbine as first-line chemotherapy in patients with advanced/metastatic HR+/HER2− breast cancer resistant to endocrine therapy: VinoMetro—AGO-B-046

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-021-03599-2 ◽

2021 ◽

Author(s):

Slavomir Krajnak ◽

Thomas Decker ◽

Lukas Schollenberger ◽

Christian Rosé ◽

Christian Ruckes ◽

...

Keyword(s):

Breast Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Metastatic Breast ◽

Progression Free Survival ◽

First Line ◽

Open Label ◽

Oral Vinorelbine ◽

Her2 Breast Cancer ◽

Line Chemotherapy

Abstract Purpose Metronomic chemotherapy (MCT) is an increasingly used treatment option in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced/metastatic breast cancer (MBC) after failure of endocrine-based therapies. Methods VinoMetro was a multicentre, open-label, single-arm, phase II study of metronomic oral vinorelbine (VRL; 30 mg/day) as a first-line chemotherapy (CT) in patients with HR+/HER2− MBC after endocrine failure. The primary endpoint was the clinical benefit rate (CBR) at 24 weeks. Results Between January 2017 and April 2019, nine patients were enrolled. The CBR was 22.2% (90% confidence interval [CI] 4.1–55.0), p = 0.211. The median progression-free survival (PFS) was 12.0 weeks (95% CI 11.3–12.7). Grade 3–4 adverse events (AEs) occurred in 22.2% of patients. One patient died of febrile neutropenia. Conclusion VinoMetro (AGO-B-046) was closed early after nine patients and occurrence of one grade 5 toxicity in agreement with the lead institutional review board (IRB). Metronomic dosing of oral VRL in HR+/HER2− MBC as first-line CT after failure of endocrine therapies showed only limited benefit in this population. Trial registration number and date of registration ClinicalTrials.gov Identifier: NCT03007992; December 15, 2016.

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