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Paclitaxel, bevacizumab, and everolimus/placebo as first-line treatment for patients with metastatic HER2-negative breast cancer: a randomized placebo-controlled phase II trial of the Sarah Cannon Research Institute

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Abstract

Amplified PI3K/Akt/mTOR signaling is common in metastatic breast cancer (MBC). The mTOR inhibitor everolimus improves progression-free survival (PFS) when added to steroidal aromatase inhibitor therapy. This randomized phase II trial compares the efficacy of paclitaxel/bevacizumab/everolimus and paclitaxel/bevacizumab/placebo as first-line treatment for MBC. Patients with untreated HER2-negative MBC were randomized (1:1) to receive 28-day cycles of paclitaxel 90 mg/m2 IV (days 1, 8, and 15) and bevacizumab 10 mg/kg IV (days 1, 15) with either everolimus 10 mg (Arm 1) or placebo (Arm 2) daily. Treatment continued (evaluation every 8 weeks) until progression or unacceptable toxicity. Treatment of 110 patients allowed detection of an improvement in median PFS from 11 to 16 months (70 % power, α = 0.10). Between August 2009 and June 2011, 113 patients (median age 58 years; 88 % ER or PR positive) were randomized (Arm 1, 56; Arm 2, 57). Patients in both arms received a median of six treatment cycles. Median PFS (95 % CI) was 9.1 months (6.8–18.8) for Arm 1, and 7.1 months (5.6–10.8) for Arm 2 (p = 0.89). Comparisons of other efficacy endpoints were also similar in the two treatment arms. Patients receiving everolimus had more anemia, stomatitis, diarrhea, rash, and arthralgia/myalgia, although the overall incidence of severe (grade 3/4) toxicity was similar. The addition of everolimus did not improve the efficacy of weekly paclitaxel/bevacizumab as first-line treatment for patients with HER2-negative MBC. These results contrast with the demonstrated efficacy of adding everolimus to either hormonal or HER2-targeted therapy in previously treated patients.

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Acknowledgments

Supported in part by a grant from Novartis

Author information

Authors and Affiliations

  1. Sarah Cannon Research Institute, 3322 West End Ave, Suite 900, Nashville, TN, 37203, USA

    Denise A. Yardley, William N. Harwin, Susan K. Morgan, Nancy W. Peacock, J. David Bass, Howard A. Burris III & John D. Hainsworth

  2. Tennessee Oncology, PLLC, 250 25th Avenue North, Nashville, TN, 37203, USA

    Denise A. Yardley, Nancy W. Peacock, Howard A. Burris III & John D. Hainsworth

  3. Wilshire Oncology Medical Group, La Verne, CA, USA

    Linda D. Bosserman

  4. Baylor Sammons Cancer Center and Texas Oncology, Dallas, TX, USA

    Joyce A. O’Shaughnessy

  5. Florida Cancer Specialists, Fort Myers, FL, USA

    William N. Harwin & Susan K. Morgan

  6. The Center for Cancer and Blood Disorders, Bethesda, MD, USA

    Victor M. Priego

Authors
  1. Denise A. Yardley
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  2. Linda D. Bosserman
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  8. J. David Bass
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Correspondence to John D. Hainsworth.

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Conflict of Interest

DAY is a consultant for Novartis. LDB is a consultant for Genentech and GSK. JAO is a consultant for Novartis. All other authors declare they have no conflict of interests.

Additional information

http://www.ClinicalTrials.gov. Identifier: NCT00915603.

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Yardley, D.A., Bosserman, L.D., O’Shaughnessy, J.A. et al. Paclitaxel, bevacizumab, and everolimus/placebo as first-line treatment for patients with metastatic HER2-negative breast cancer: a randomized placebo-controlled phase II trial of the Sarah Cannon Research Institute. Breast Cancer Res Treat 154, 89–97 (2015). https://doi.org/10.1007/s10549-015-3599-5

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  • DOI: https://doi.org/10.1007/s10549-015-3599-5

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