Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer

Javier Cortes, J. Perez-Garcia, C. Levy, P. Gómez Pardo, H. Bourgeois, S. Spazzapan, N. Martínez-Jañez, T. C. Chao, M. Espié, J. M. Nabholtz, X. Gonzàlez Farré, V. Beliakouski, J. Román Garciá, E. Holgado, M. Campone

Research output: Contribution to journalArticle

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Abstract

Background: There is no standard treatment after progression on second-line chemotherapy for metastatic breast cancer (MBC). We compared vinflunine with physician's choice of alkylating agent (AA) for patients with heavily pretreated MBC. Patients and methods: In this open-label phase III trial, patients with MBC were included if they had received at least two prior chemotherapy regimens for MBC and had received anthracycline, taxane, antimetabolite and vinca alkaloid therapy. Patients were no longer candidates for these chemotherapies because of resistance and/or intolerance. Patients were randomised to either vinflunine 280 mg/m2 intravenously every 3 weeks (q3w) or AA monotherapy q3w. Stratification factors were performance status, number of prior chemotherapy lines for MBC, disease measurability and study site. The primary end point was overall survival (OS). Results: A total of 594 patients were randomised (298 to vinflunine, 296 to AA). There was no difference between treatment arms in OS (hazard ratio 1.04, P=0.67; median 9.1 months for vinflunine versus 9.3 months for AA), progression-free survival (hazard ratio 0.94, P=0.49; median 2.5 versus 1.9 months, respectively) or overall response rate (6% versus 4%, respectively). However, the disease control rate was significantly higher with vinflunine than AA (44% versus 35%, respectively; P=0.04). The most common adverse events (any grade) were haematological and gastrointestinal disorders and asthenia in both arms. The most common grade 3/4 adverse events were neutropenia (19% versus 11% with vinflunine versus AA, respectively) and asthenia (10% versus 4%). Conclusions: Vinflunine 280 mg/m2 q3w did not improve OS compared with the physician's choice of AA as third- or later-line therapy for MBC. Vinflunine demonstrated an acceptable safety profile, suggesting that vinflunine 320 mg/m2 merits evaluation.

Original languageEnglish
Pages (from-to)881-887
Number of pages7
JournalAnnals of Oncology
Volume29
Issue number4
DOIs
Publication statusPublished - Apr 1 2018

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Alkylating Agents
Breast Neoplasms
Asthenia
Drug Therapy
Survival
Vinca Alkaloids
Physicians
vinflunine
Antimetabolites
Breast Diseases
Anthracyclines
Therapeutics
Neutropenia
Disease-Free Survival
Safety

Keywords

  • Alkylating agent
  • Metastatic breast cancer
  • Phase III
  • Vinflunine

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer. / Cortes, Javier; Perez-Garcia, J.; Levy, C.; Gómez Pardo, P.; Bourgeois, H.; Spazzapan, S.; Martínez-Jañez, N.; Chao, T. C.; Espié, M.; Nabholtz, J. M.; Farré, X. Gonzàlez; Beliakouski, V.; Garciá, J. Román; Holgado, E.; Campone, M.

In: Annals of Oncology, Vol. 29, No. 4, 01.04.2018, p. 881-887.

Research output: Contribution to journalArticle

Cortes, J, Perez-Garcia, J, Levy, C, Gómez Pardo, P, Bourgeois, H, Spazzapan, S, Martínez-Jañez, N, Chao, TC, Espié, M, Nabholtz, JM, Farré, XG, Beliakouski, V, Garciá, JR, Holgado, E & Campone, M 2018, 'Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer', Annals of Oncology, vol. 29, no. 4, pp. 881-887. https://doi.org/10.1093/annonc/mdy051
Cortes, Javier ; Perez-Garcia, J. ; Levy, C. ; Gómez Pardo, P. ; Bourgeois, H. ; Spazzapan, S. ; Martínez-Jañez, N. ; Chao, T. C. ; Espié, M. ; Nabholtz, J. M. ; Farré, X. Gonzàlez ; Beliakouski, V. ; Garciá, J. Román ; Holgado, E. ; Campone, M. / Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer. In: Annals of Oncology. 2018 ; Vol. 29, No. 4. pp. 881-887.
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T1 - Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer

AU - Cortes, Javier

AU - Perez-Garcia, J.

AU - Levy, C.

AU - Gómez Pardo, P.

AU - Bourgeois, H.

AU - Spazzapan, S.

AU - Martínez-Jañez, N.

AU - Chao, T. C.

AU - Espié, M.

AU - Nabholtz, J. M.

AU - Farré, X. Gonzàlez

AU - Beliakouski, V.

AU - Garciá, J. Román

AU - Holgado, E.

AU - Campone, M.

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N2 - Background: There is no standard treatment after progression on second-line chemotherapy for metastatic breast cancer (MBC). We compared vinflunine with physician's choice of alkylating agent (AA) for patients with heavily pretreated MBC. Patients and methods: In this open-label phase III trial, patients with MBC were included if they had received at least two prior chemotherapy regimens for MBC and had received anthracycline, taxane, antimetabolite and vinca alkaloid therapy. Patients were no longer candidates for these chemotherapies because of resistance and/or intolerance. Patients were randomised to either vinflunine 280 mg/m2 intravenously every 3 weeks (q3w) or AA monotherapy q3w. Stratification factors were performance status, number of prior chemotherapy lines for MBC, disease measurability and study site. The primary end point was overall survival (OS). Results: A total of 594 patients were randomised (298 to vinflunine, 296 to AA). There was no difference between treatment arms in OS (hazard ratio 1.04, P=0.67; median 9.1 months for vinflunine versus 9.3 months for AA), progression-free survival (hazard ratio 0.94, P=0.49; median 2.5 versus 1.9 months, respectively) or overall response rate (6% versus 4%, respectively). However, the disease control rate was significantly higher with vinflunine than AA (44% versus 35%, respectively; P=0.04). The most common adverse events (any grade) were haematological and gastrointestinal disorders and asthenia in both arms. The most common grade 3/4 adverse events were neutropenia (19% versus 11% with vinflunine versus AA, respectively) and asthenia (10% versus 4%). Conclusions: Vinflunine 280 mg/m2 q3w did not improve OS compared with the physician's choice of AA as third- or later-line therapy for MBC. Vinflunine demonstrated an acceptable safety profile, suggesting that vinflunine 320 mg/m2 merits evaluation.

AB - Background: There is no standard treatment after progression on second-line chemotherapy for metastatic breast cancer (MBC). We compared vinflunine with physician's choice of alkylating agent (AA) for patients with heavily pretreated MBC. Patients and methods: In this open-label phase III trial, patients with MBC were included if they had received at least two prior chemotherapy regimens for MBC and had received anthracycline, taxane, antimetabolite and vinca alkaloid therapy. Patients were no longer candidates for these chemotherapies because of resistance and/or intolerance. Patients were randomised to either vinflunine 280 mg/m2 intravenously every 3 weeks (q3w) or AA monotherapy q3w. Stratification factors were performance status, number of prior chemotherapy lines for MBC, disease measurability and study site. The primary end point was overall survival (OS). Results: A total of 594 patients were randomised (298 to vinflunine, 296 to AA). There was no difference between treatment arms in OS (hazard ratio 1.04, P=0.67; median 9.1 months for vinflunine versus 9.3 months for AA), progression-free survival (hazard ratio 0.94, P=0.49; median 2.5 versus 1.9 months, respectively) or overall response rate (6% versus 4%, respectively). However, the disease control rate was significantly higher with vinflunine than AA (44% versus 35%, respectively; P=0.04). The most common adverse events (any grade) were haematological and gastrointestinal disorders and asthenia in both arms. The most common grade 3/4 adverse events were neutropenia (19% versus 11% with vinflunine versus AA, respectively) and asthenia (10% versus 4%). Conclusions: Vinflunine 280 mg/m2 q3w did not improve OS compared with the physician's choice of AA as third- or later-line therapy for MBC. Vinflunine demonstrated an acceptable safety profile, suggesting that vinflunine 320 mg/m2 merits evaluation.

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