QuoteReplyTopic: Any BRCA neg done carboplatin taxane after ACT? Posted: Apr 27 2016 at 3:46pm
Hi,
I have a recurrence (small tumor, four years out, NED). I did ACT first time around, and my recommended tx option is carboplatin taxane combo. I am BRCA negative and this is shown to have less benefit.
Anyone else with BRCA negative who had to find a second line of defense? What was it? What did you learn? How did it go?
I tried posting earlier but thought this newly phrased posting might elicit more response.
Unfortunately both my sister and i are BRCA Pos. I took carboplatin after a clinical trial "G" drug with Taxol, AC followed by carboplatin. My sister currently taking carboplatin and taxane for ovarian cancer (TNBC survivor) with promising results. Have you talked to your doctor about benefits of a clinical trial? PD1 has had very promising results for different types of cancers, now there's a trial for Triple Negative. There is a phase 1 & 2 trial I believe. Wish you the best.
Hey, my wife is BRCA- and had the carboplatin-taxotere combination as an adjuvant therapy following her initial ACT and mastectomy but before radiation. They weren't able to see the results, as the primary tumor had already been removed, but she had a recurrence shortly after the radiation finished, so the assumption was that it wasn't helpful. The side effects were fairly tolerable, in comparison with the ACT, but I think I would question the usefulness (at the time we didn't realize that platinum treatments are more effective with BRCA+). To me it's especially illogical to do if you've already received taxol, which she had (but I'm not an expert!).
Thank you for your reply. And I am so sorry it didn't work. This is my fear too- that for BRCA- it won't work, although it's good to hear the affects weren't as bad as ACT because that was really rough. I am so sorry you all had to go through that again, and I really appreciate your response.
My wife had Carbo/Gem chemo before surgery, it reduced tumor from 5cm to 1.2cm and killed cancer in 4 lymph nodes (pCR) she is BRCA- and neg for another 5 genes they tested for(AmbreyGenomics) and found out androgen negative also.
She couldn't have AC on 2015 diagnosis b/c she had it in 2008 and would exceed limit for Adrymycin ("A), and having squamous features, Carbo/Gem was recommd. She had Taxol after surgery.
Controversy Continues Over Platinum for TNBC Patients
SAN ANTONIO– Oncologists are
split over the use of platinum compounds as adjuvant or neoadjuvant
therapy for triple-negative breast cancer patients, a rift likely to
continue until definitive outcome data become available several years
from now.
“In the U.S., I would say that about half of all medical oncologists
are now in a fairly routine manner giving carboplatin in this setting,”
Dr. Eric P. Winer estimated at the San Antonio Breast Cancer Symposium.
He’s not among them.
“Is
carboplatin ready for prime time use in the adjuvant or neoadjuvant
setting in triple-negative breast cancer? I personally feel we first
need a definitive study showing improvement in disease-free survival
and/or overall survival, or something close to that,” said Dr. Winer,
chief of the division of women’s cancers at the Dana-Farber Cancer
Institute and professor of medicine at Harvard Medical School, Boston.
Proponents of platinum salts cite two positive phase II randomized trials – GeparSixto and CALGB 40603
– which demonstrated significantly higher pathologic complete response
(pCR) rates in patients with stage II or III triple-negative breast
cancer (TNBC) with the addition of carboplatin to neoadjuvant
chemotherapy.
The pro-platinum camp points to evidence
suggesting a pCR in women with TNBC appears to be a good surrogate
endpoint for event-free survival and overall survival, as shown in a
recent meta-analysis by Dr. Patricia Cortazar of the Food and Drug
Administration and her coworkers. The investigators concluded that pCR
in response to neoadjuvant therapy with various regimens was associated
with a 76% improvement in event-free survival and an 84% improvement in
overall survival in 557 women with TNBC (Lancet 2014;384:164-72).
“The two phase II studies are going in the same direction,” observed Dr. Gunter von Minckwitz of the German Breast Group
and principal investigator in the GeparSixto trial. “We have surveyed
our group of investigators, and they are all using platinum in
triple-negative breast cancer. The German guidelines say you can, but
you don’t have to.”
But Dr. Winer, and by his estimate roughly half of all American medical oncologists, remain unconvinced.
“I
think we should all keep in mind that pCR is a marker of better
outcome, it’s not necessarily a required step in the process,” he said.
He’s
leery of relying upon pCR as a surrogate endpoint in light of the
deeply disappointing BEATRICE experience. The phase III BEATRICE trial
included nearly 2,600 women with TNBC who were randomized to adjuvant
chemotherapy alone or in combination with bevacizumab. The bevacizumab
group had a higher pCR, but no improvement in disease-free survival or
overall survival (Lancet Oncol. 2013;14:933-42).
“I
would hate to see us all indiscriminately adding platinum to standard
regimens, increasing toxicity, particularly if it is not associated with
long-term benefit,” Dr. Winer said. “And even if it is associated with
long-term benefit, I want to tease out who really benefits and which
triple-negative patients are most sensitive to these agents.”
Progress
is occurring in this area, he added. In GeparSixto, the addition of
neoadjuvant carboplatin to paclitaxel and nonpegylated liposomal
doxorubicin was associated with a 66.7% pCR rate in the subgroup of TNBC
patients with a BRCA 1 or 2 germline mutation and a 43.5% rate in those
without such mutations (Lancet Oncol. 2014;15:747-56).
Moreover, in the phase III Triple Negative Breast Cancer Trial (TNT)
presented at this year’s San Antonio symposium, Dr. Andrew N.J. Tutt
reported that in a prespecified analysis of the small subgroup
comprising 43 BRCA mutation-positive patients, the objective response
rate was 68% in those randomized to carboplatin, compared with 33% in
those assigned to docetaxel. Moreover, mean progression-free survival
was 6.8 months with carboplatin, significantly better than the 4.8
months with docetaxel or the 3.1 months in carboplatin-treated patients
without a BRCA 1/2 mutation.
The TNT trial included 376 patients
with metastatic or recurrent locally advanced TNBC randomized to single
agent therapy. While the study provides no evidence of a superior
response to carboplatin, compared with docetaxel in unselected patients
with metastatic TNBC, it does support BRCA 1/2 mutation genotyping as
part of decision making regarding therapy in metastatic TNBC and
familial breast cancer, according to Dr. Tutt, professor of breast
oncology at the Institute of Cancer Research, London.
The trial also tested the utility of Myriad Genetics’ novel Homologous Recombination Deficiency (HRD) score as a predictor of platinum-responsiveness of TNBC and concluded it was without benefit.
Dr.
Winer noted that TNBC accounts for only about 15% of breast cancers.
Still, that’s roughly 35,000 new cases per year in the United States
alone – and TNBC is responsible for a disproportionate degree of breast
cancer mortality.
“Perhaps in patients with BRCA 1 or 2
mutations, we’re getting close to thinking that platinum may be a
standard, but even here I would await the completion of ongoing trials
before we embrace that concept,” he said.
Among these studies is
the 12-258 INFORM trial, a multicenter study in which 166 newly
diagnosed breast cancer patients with BRCA1 or 2 mutations are being
randomized to preoperative cisplatin or doxorubicin/cyclophosphamide.
Dr. William M. Sikov, principal investigator for the CALGB 40603 trial (J. Clin. Oncol. 2015;33:13-21),
predicted there will be little crossover between the platinum-user and
nonuser camps until definitive trials report whether the therapy
improves relapse-free or overall survival.
“One group will say,
‘There’s an absolute increase in pathologic complete response with
carboplatin in these two studies, and I’m convinced it’s a beneficial
drug in these patients.’ It’s inexpensive, it’s available, although not
approved for triple negative breast cancer, and it has some hematologic
toxicities. But we have no long-term outcomes yet. I don’t think the TNT
results will change anyone’s mind,” according to Dr. Sikov of Women and
Infants Hospital in Providence, R.I.
Dr. Winer reported
receiving research funding from Genentech. Dr. Sikov serves as a
consultant to AbbVie and Celgene. Dr. Tutt reported having no financial
conflicts.
Wow, Gordon. This is so helpful. I really appreciate it. Such good news to hear about your wife, and I am keeping my fingers tightly crossed for your results at the end of May.
Thanks for your reply, I have no idea if Carboplatin/Gemzar worked on my wife, but it killed the small mets in the lymph nodes, and 75% of her tumor as an neoadjuvant (chemo before surgery) but maybe Donna has more recent statistics on if the platinum From everything I have read, Carbo/Gem seems to have an edge if administered before surgery (neoadjuvant chemo)especially for BRCA +(positive) genes detected... doctors seem to be assessing it's effectiveness after surgery, but they seem to be split 50/50 on this course of action, again, this is my total assumption, after reading what I can find.
The doctors are equally concerned about toxicity,for administering platinum agents...
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