Adding the chemotherapy drug carboplatin to standard treatment improved outcomes for women with triple-negative breast cancer in two studies presented today at the 2013 San Antonio Breast Cancer Symposium. Both measured pathological complete response (pCR), which is recognized as a positive marker for overall survival. The second study also showed improved outcomes using bevacizumab (Avastin).
Combining carboplatin and the targeted drug veliparib and adding the combo to standard presurgery chemotherapy nearly doubled the response rate for women with TNBC, according to results from the I-SPY 2 trial.
In the stage II trial, 52 percent of the patients with TNBC who received veliparib, carboplatin and standard paclitaxel followed by anthracycline-based chemotherapy reached a pathological complete response (pCR). This compared to 26 percent for those who received standard therapy alone. Participants had tumors larger than 2.5 centimeters, so were either stage 2 or 3.
A pCR is defined as no residual invasive cancer detected in breast tissue and lymph nodes removed during surgery, Women with a pCR have a greater chance of long-term survival compared with women who do not. The Federal Drug Administration is increasingly using this as a measure for the approval of chemotherapy drugs.
“These results predict that the veliparib-carboplatin regimen is highly likely to be superior to the control regimen for triple-negative breast cancer in a phase III trial,” said Hope Rugo, M.D., professor of medicine and director of breast oncology and clinical trials education at the UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco.
This is a potent cocktail, although Rugo said most women tolerated it well.
The research is part of an ongoing series of studies called I-SPY 2, designed to learn which patients respond better to which therapies as the trial progresses. Those who respond well to a particular regimen remain on it; those who do not are changed to different drugs.
Seventy-one patients enrolled in I-SPY 2 were randomly assigned to the veliparib plus carboplatin regimen in combination with paclitaxel. Among these patients, 38 had triple-negative breast cancer and 33 had hormone receptor-positive and HER2-negative breast cancer.
The addition of carboplatin to standard neoadjuvant chemotherapy increased the pCR in women with TNBC from 46 percent to 60 percent, according to a phase II clinical trial conducted by the CALGB/Alliance 40603.
The research included 443 patients with operable, stage 2 or 3 triple-negative breast cancer who received carboplatin plus standard neoadjuvant chemotherapy of pacilataxel and AC (cyclophosphamide, doxorubicin). Surgery was performed from four to eight weeks after the completion of neoadjuvant treatment.
The most common side effect was neutropenia, or abnormally low levels of neutrophils in the blood, leading to increased susceptibility to infection.
The CALGB study also studied bevacizumab combined with standard chemotherapy and found an increased response as opposed to using standard therapy only.
Fifty-nine percent of those taking bevacizumab plus standard therapy reached a pathological complete response as opposed to 48 percent of those on standard therapy alone.
“Our study was designed to find out if adding either carboplatin or bevacizumab to standard preoperative chemotherapy would increase the percentage of patients in whom cancer is eliminated before surgery,” said William M. Sikov, M.D., F.A.C.P., associate professor of medicine at the Warren Alpert Medical School of Brown University in Providence, R.I. “We are excited to report that adding either therapy significantly increased the percentage of patients in whom cancer was eliminated from the breast, and that adding both was even more effective.”
Patients taking bevacizumab has slightly more neutropenia than those on other drugs; some also had elevated blood pressure.
Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.
[S5-01] Impact of the addition of carboplatin (Cb) and/or bevacizumab (B) to neoadjuvant weekly paclitaxel (P) followed by dose-dense AC on pathologic complete response (pCR) rates in triple-negative breast cancer (TNBC): CALGB 40603 (Alliance)
Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione C, Tolaney S, Kuzma CS, Pluard TJ, Somlo G, Port E, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis C, Winer EP. Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; University of Texas M.D. Anderson Cancer Center, Houston, TX; UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC; New York University Medical Center, New York, NY; Alliance Statistical Center, Durham, NC; Dana Farber Cancer Institute, Boston, MA; Southeast Cancer Control Consortium, Winston-Salem, NC; Washington University-St. Louis Medical Center, St. Louis, MO; City of Hope Comprehensive Cancer Center, Duarte, CA; Mount Sinai Medical Center, New York, NY; Patient Advocates in Research, Danville, CA; University of Chicago Medical Center, Chicago, IL; Memorial Sloan-Kettering Cancer Center, New York, NY
[S5-02] Veliparib/carboplatin plus standard neoadjuvant therapy for high-risk breast cancer: First efficacy results from the I-SPY 2 TRIAL
Rugo HS, Olopade O, DeMichele A, van 't Veer L, Buxton M, Hylton N, Yee D, Chien AJ, Wallace A, I-SPY 2 Site PI's, Lyandres J, Davis S, Sanil A, Berry D, Esserman L. University of California San Francisco Helen Diller Family Comprehensive Cancer Center; University of Chicago; University of Pennslyvania; University of Minnesota; University of Texas MD Anderson Cancer Center; I-SPY 2 Clinical Trial Sites; University of California San Diego; Berry Consultants, LLC