CHICAGO, IL—Established biomarkers failed to predict response to platinum in patients with metastatic triple-negative breast cancer (mTNBC), a study concluded at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.
However, “homologous recombination deficiency [HRD] assays may identify sporadic TNBC tumors that are BRCA1/2-like and responsive to platinum chemotherapy,” said Steven J. Isakoff, MD, PhD, of Massachusetts General Hospital Cancer Center in Boston, MA.
Previously, a multicenter, single-arm, phase 2 study of single-agent platinum in 86 patients with mTNBC found that BRCA1/2 carriers (n=11) had an objective response rate (ORR) of 54.5% (95% CI: 23.4%-83.3%) versus 19.7% (95% CI: 10.9%-31.3%) in noncarriers (n=66; P= 0.022). In nine patients, BRCA1/2 status was unknown. Overall, ORR was 25.6% (95% CI: 16.8%-36.1%), and six long-term responders remain disease free at median follow-up of approximately 4 years, Dr. Isakoff reported.
However, although the BRCA1/2 germline mutation carriers had a significantly higher response rate, this was not found to predict either longer progression-free survival or overall survival.
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In this analysis, the investigators explored biomarkers of response to platinum in that study, in which patients received cisplatin 75mg/m2 or carboplatin AUC 6 every 3 or 4 weeks, by physician choice. Co-primary endpoints were ORR in first- or second-line treatment of mTNBC and p63/p73 expression by reverse transcriptase polymerase chain reaction (RT-PCR) as a biomarker of response.
Among the 61 patients evaluable for p63/p73 expression by RT-PCR as a predictor of response, 28 (46%) had the prespecified p63/p73 ratio greater than or equal to 2, which did not predict response to platinum (ORR, 18% vs. 27% in p63/p73 ≥ 2 vs. < 2, respectively; P = 0.54). This study endpoint was not met.
When the p63/p73 ratio was evaluated in seven patients who had no prior treatment for TNBC, five had a complete or partial response and two had disease progression (P = 0.0308). These responses correlated with a higher p63/p73 ratio and supports results seen in neoadjuvant platinum therapy, he said.