CHICAGO – Carboplatin or cisplatin monotherapy has significant activity as a first- or second-line treatment against metastatic triple-negative breast cancer, according to Dr. Steven J. Isakoff.
The overall response rate to therapy with one of the platinum compounds was 30.2% – 4.7% complete responses and 25.6% partial responses, Dr. Isakoff of Massachusetts General Hospital cancer center, Boston, and his colleagues in the Translational Breast Cancer Research Consortium found.
Subgroup analyses of the multicenter single-arm trial suggested a higher response rate with cisplatin (37%) than with carboplatin (23%), but this was not a head-to-head study, and the results should be interpreted with caution because physicians were allowed to choose one of the two agents at their own discretion, which could introduce bias into the results, Dr. Isakoff said at the meeting.
The drugs were generally well tolerated with manageable toxicities; some patients have received as many as 23 cycles, he said in an interview.
The investigators also looked at the utility of two members of the p53 family of oncogenic transcription factors, p63 and p73, for predicting response to platinum agents in triple-negative breast cancer (tumors lacking receptors for estrogen, progesterone, or HER2/neu that are targeted by other forms of therapy).
"As information about the activity of platinum in BRCA carriers has become recognized, people are thinking about it more in triple-negative breast cancer," Dr. Isakoff said. "We still don’t know whether triple-negative breast cancer is particularly sensitive to platinum or is just sensitive to chemotherapy, and I think it’s going to take some of the randomized studies that are going on now in Europe, such as the TNT trial comparing carboplatin to docetaxel, to see whether there’s something special about triple negative and platinum."
The TBCRC009 study enrolled 86 patients with triple-negative breast cancer. The patients were assigned on the treating physician’s choice to receive either cisplatin at 75mg/m2 IV every 3 weeks, or carboplatin to an area under the curve of 6 every 3 weeks.
In addition to the overall response rates noted here, the authors calculated a clinical benefit rate (a combination of complete and partial response and stable disease) of 34%.
Median progression-free survival (PFS) was 89 days. Thirty-three percent of patients had a PFS of less than 6 weeks, and another 33% had a PFS longer than 6 months. Among responders, a median PFS was 242 days. Responders had a median of nine chemotherapy cycles.
In subgroup analyses, platinum compounds were associated with a 33% response rate when used as first-line agents, and 17% when used in the second line. Only 17 patients received platinum as a second-line therapy, however.
The patients generally tolerated the drugs well. There was one case each of grade 4 neutropenia and hypertension. Grade 3 events included nine cases of fatigue, six of neutropenia, five of anemia, and four of hyponatremia.
"In general, it was well tolerated. We didn’t see unexpected toxicities with platinum, and we modified things with dose reductions as appropriate. It was not a common event to come off therapy due to toxicity," Dr. Isakoff said.
The investigators continue to collect data to determine whether p63/p73 expression can be a biomarker for response to platinum agents. The authors are also conducting BRCA mutation, molecular subtype, and circulating tumor cell analyses.
"This study was well designed with prospective powering for the p63/p73 correlative end point," said Dr. Stephen K.L. Chia of the British Columbia Cancer Agency and the University of British Columbia, in Vancouver, the invited discussant.
The rationale for investigating p63/p73 as a predictive biomarker is sound because these markers can be found in about 35%-40% of triple-negative breast cancers, he said. Questions that need to be addressed include whether there is a change in expression of the markers in metastatic relapse, and whether the heterogeneous group of triple-negative breast cancers can be further refined through molecular subtyping.
The study was funded by the AVON Foundation, Breast Cancer Research Foundation, Susan D. Komen for the Cure, Golfers Against Cancer, the Tracey Davis Breast Cancer Research Fund, and investigator awards from the NCI-AVON Partners for Progress, Harvard-MIT, and the Dana-Farber/Harvard Cancer Center. The authors said they had no other relevant financial disclosures.