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Final results of a phase II study of nab-paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer

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Abstract

In order to examine the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-P) in combination with bevacizumab (B) and gemcitabine (G) for the first-line treatment of patients with HER2-negative metastatic breast cancer (MBC). In this single-center, open-label phase II trial, patients with HER2-negative MBC received gemcitabine 1500 mg/m2, nab-paclitaxel 150 mg/m2, and bevacizumab 10 mg/kg (each administered intravenously) on days 1 and 15 of a 28-day cycle. The primary end point was progression free survival (PFS); secondary end points were overall response rate (ORR), complete (CR) and partial (PR) response rates, clinical benefit (ORR + stable disease), overall survival (OS), and safety. Thirty patients were enrolled. One patient was ineligible and was not included in analysis. Median PFS was 10.4 months (95% CI: 5.6–15.2 months). ORR was 75.9%, comprising eight (27.6%) CRs and 14 (48.3%) PRs; five patients had stable disease (SD) and two patients (6.9%) had progressive disease (PD) as their best response. The clinical benefit rate was 93.1% (27/29) in the overall group and 84.6% in the triple-negative cohort (11/13). The 18-month survival rate was 77.2% (95% CI: 51.1–90.5%). Eight (27.6%) patients experienced grade 3 or 4 toxicity: grade 4 neutropenic fever (n = 1) and grade 3 infection (n = 6), leukopenia, thrombocytopenia, peripheral neuropathy, seizure, shortness of breath, hematuria, and cardiac tamponade (one each). First-line therapy with nab-P, B, and G demonstrated a median PFS of 10.4 months and a 75.9% ORR with acceptable toxicity; this novel combination warrants investigation in a randomized study.

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References

  1. American Cancer Society (2009) Breast cancer facts and figures 2009. American Cancer Society Inc, Atlanta

    Google Scholar 

  2. O’Shaughnessy J (2005) Extending survival with chemotherapy in metastatic breast cancer. Oncologist 10(suppl 3):20–29

    Article  PubMed  Google Scholar 

  3. Mayer EL, Burstein HJ (2007) Chemotherapy for metastatic breast cancer. Hematol Oncol Clin North Am 21:257–272

    Article  PubMed  Google Scholar 

  4. Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desia N, Bhar P et al (2005) Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol 23(31):7794–7803

    Article  CAS  PubMed  Google Scholar 

  5. Gradishar WJ, Krasnojon D, Cheporov S, Makhson AN, Manikhas G, Clawson A et al (2009) Significantly longer progression-free survival with nab-Paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol 27:3611–3619

    Article  CAS  PubMed  Google Scholar 

  6. Tomao S, Romiti A, Tamao F, Di Seri M, Caprio G, Spinelli GP et al (2006) A phase II trial of a biweekly combination of paclitaxel and gemcitabine in metastatic breast cancer. BMC Cancer 6:137

    Article  PubMed  Google Scholar 

  7. Albain KS, Nag SM, Calderillo-Ruiz G, Jordaan JP, Llombart AC, Pluzanska A et al (2008) Gemcitabine plus paclitaxel versus paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment. J Clin Oncol 26:3950–3957

    Article  PubMed  Google Scholar 

  8. Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez E et al (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–2676

    Article  CAS  PubMed  Google Scholar 

  9. Gray R, Bhattacharya S, Bowden C, Miller K, Comis R (2009) Independent Review of E2100: A phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer. J Clin Oncol 27:4966–4972

    Article  CAS  PubMed  Google Scholar 

  10. Danso MA, Blum JL, Robert NJ, Krekow L, Rotche R, Smith DA et al (2008) Phase II trial of weekly nab-paclitaxel in combination with bevacizumab as first-line treatment in metastatic breast cancer. J Clin Oncol 26(suppl):1075

    Google Scholar 

  11. Lobo C, Lopes G, Silva O, Gluck S (2007) Paclitaxel albumin-bound particles (abraxaneTM) in combination with bevacizumab with or without gemcitabine: Early experience at the University of Miami/Braman Family Breast Cancer Institute. Biomed Pharmacother 61:531–533

    Article  CAS  PubMed  Google Scholar 

  12. Collett D (2003) Modeling survival data in medical research. Chapman & Hill, London

    Google Scholar 

  13. Conlin AK, Hudis CA, Bach A, Moynahan M, Lake D, Forero-Torres A et al (2009) Randomized phase II trial of nanoparticle albumin-bound paclitaxel in three dosing schedules with bevacizumab as first-line therapy for HER2-negative metastatic breast cancer. J Clin Oncol 27(Suppl):1006

    Google Scholar 

  14. Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, Brambilla C et al (1976) Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med 294:405–410

    Article  CAS  PubMed  Google Scholar 

  15. Sledge GW, Neuberg D, Bernardo JN, Ingle JN, Martino S, Rowinsky EK et al (2003) Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: An Intergroup Trial (E1193). J Clin Oncol 21(4):588–592

    Article  PubMed  Google Scholar 

  16. O’Shaughnessy JA, Blum JL, Sandbach JF, Savin M, Fenske E, and Hawkins MJ (2004) Weekly nanoparticle albumin paclitaxel (Abraxane) results in long-term disease control in patients with taxane-refractory metastatic breast cancer. Paper presented at the 27th Annual San Antonio Breast Cancer Symposium; 2004 December 8–11, San Antonio (TX). Abstract1070

  17. Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L et al (2005) Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 23:792–799

    Article  CAS  PubMed  Google Scholar 

  18. Ibrahim NK, Desai N, Legha S, Soon-Shiong P, Theriault RL, Rivera E et al (2002) Phase I and pharmacokinetic study of ABI-007, a cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. Clin Cancer Res 8(5):1038–1044

    CAS  PubMed  Google Scholar 

  19. Robert N, Leyland-Jones B, Asmar L, Belt R, Ilegbodu D, Loesch D et al (2006) Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol 24:2786–2792

    Article  CAS  PubMed  Google Scholar 

  20. Northfelt DW (2008) Paclitaxel albumin-stabilized nanoparticle formulation, gemcitabine, and bevacizumab in treating patients with metastatic breast cancer. 2008 Clinicaltrials.gov. http://clinicaltrials.gov/ct2/show/NCT00662129?term=NCT00662129&rank=1. Assessed 28 Jan 2010

  21. Sledge GW, Miller K, Moisa C, Gradishar W (2007) Safety and efficacy of capecitabine (C) plus bevacizumab (B) as first-line in metastatic breast cancer. Paper presented at the 2007 ASCO Annual Meeting; 2007 June 1–5, Chicago (IL). Abstract 1013

  22. Colon-Otero G, Smallridge RC, Solberg LA, Keith TD, Woodward TA, Willis FB et al (2008) Disparities in participation in cancer clinical trials in the United States. Cancer 112(3):447–454

    Article  PubMed  Google Scholar 

  23. Murthy VH, Krumholz HM, Gross CP (2004) Participation in cancer clinical trials: race-, sex-, and age-based disparities. JAMA 291(22):2720–2726

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We appreciate the efforts of Emilio Weiss, the Research Pharmacist. We would like to thank Lilly USA, Genentech, Inc., and Abraxis BioScience for their financial support and drug supply.

Conflict of interest

Statement Stefan Glück received research funding from Lilly USA, Genentech, Inc., and Abraxis BioScience.

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Authors and Affiliations

  1. Florida Cancer Specialists and Research Institute, Gainesville, FL, USA

    Christopher Lobo

  2. The Johns Hopkins Singapore International Medical Centre, Singapore, Singapore

    Gilberto Lopes

  3. The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Gilberto Lopes

  4. Division of Hematology/Oncology, Department of Medicine, Sylvester Comprehensive Cancer Center, Braman Family Breast Cancer Institute Miller School of Medicine in Miami, The University of Miami, 1475 NW 12 Avenue, SCCC, Suite 3510 (D8-4), Miami, FL, 33136, USA

    Odalys Baez, Aurelio Castrellon, Annapoorna Ferrell, Connie Higgins, Erin Hurley, Judith Hurley, Isildinha Reis, Stephen Richman, Pearl Seo, Orlando Silva, Joyce Slingerland, Keleni Tukia, Catherine Welsh & Stefan Glück

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  1. Christopher Lobo
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  2. Gilberto Lopes
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  14. Keleni Tukia
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  15. Catherine Welsh
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  16. Stefan Glück
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Correspondence to Stefan Glück.

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Lobo, C., Lopes, G., Baez, O. et al. Final results of a phase II study of nab-paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer. Breast Cancer Res Treat 123, 427–435 (2010). https://doi.org/10.1007/s10549-010-1002-0

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  • DOI: https://doi.org/10.1007/s10549-010-1002-0

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