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
I-SPY
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.
CALGB/Alliance 40603
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.
Bevacizumab (Avastin)
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.
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SOURCES:
SOURCES:
[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
3 comments:
I am beginning chemo on March 7th with DD AC x 4 and taxol x 12. Is there any evidence to doing the taxol first and then the AC? Someone on breastcancer.org said that her MO follows the MD Anderson standard of care and that they follow this. I am not sure of the reason.Here is an article I found from 2011, but are there any followups?
http://forum.tnbcfoundation.org/attention-newbies-important-new-chemo-study_topic7771_page8.html
The sequencing depends on a lot of factors, so it is hard to tell which one is best overall. The standard had been what you are having, but some docs are switching to taxol first. Some women tolerate taxol better than others, and some have problems with adriamycin. Either way is an accepted approach to treating TNBC, so I would be comfortable with either approach. I long for the day when chemo itself is replaced with something less toxic. For now, though, it works. Hugs and good luck.
Any possibility that Carboplatin could be combined with TAC in the adjuvant stage since the response was so overwhelmingly "positive" in the neoadjuvant stage? About to start TAC every 3 weeks x 6 then 30 rounds of rads.
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