| Autor: |
Yardley DA; Sarah Cannon Research Institute, 3322 West End Ave, Suite 900, Nashville, TN, 37203, USA. dyardley@tnonc.com.; Tennessee Oncology, PLLC, 250 25th Avenue North, Nashville, TN, 37203, USA. dyardley@tnonc.com., Bosserman LD; Wilshire Oncology Medical Group, La Verne, CA, USA., O'Shaughnessy JA; Baylor Sammons Cancer Center and Texas Oncology, Dallas, TX, USA., Harwin WN; Sarah Cannon Research Institute, 3322 West End Ave, Suite 900, Nashville, TN, 37203, USA.; Florida Cancer Specialists, Fort Myers, FL, USA., Morgan SK; Sarah Cannon Research Institute, 3322 West End Ave, Suite 900, Nashville, TN, 37203, USA.; Florida Cancer Specialists, Fort Myers, FL, USA., Priego VM; The Center for Cancer and Blood Disorders, Bethesda, MD, USA., Peacock NW; Sarah Cannon Research Institute, 3322 West End Ave, Suite 900, Nashville, TN, 37203, USA.; Tennessee Oncology, PLLC, 250 25th Avenue North, Nashville, TN, 37203, USA., Bass JD; Sarah Cannon Research Institute, 3322 West End Ave, Suite 900, Nashville, TN, 37203, USA., Burris HA 3rd; Sarah Cannon Research Institute, 3322 West End Ave, Suite 900, Nashville, TN, 37203, USA.; Tennessee Oncology, PLLC, 250 25th Avenue North, Nashville, TN, 37203, USA., Hainsworth JD; Sarah Cannon Research Institute, 3322 West End Ave, Suite 900, Nashville, TN, 37203, USA. john.hainsworth@scresearch.net.; Tennessee Oncology, PLLC, 250 25th Avenue North, Nashville, TN, 37203, USA. john.hainsworth@scresearch.net. |
| Abstrakt: |
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/m(2) 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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