Sufficient tissue was available from 32 patients, five with the BRCA1/2 mutation (three germline BRCA1, one somatic BRCA1, and one germline BRCA2), and 27 with BRCA1/2 wild type (four BRCA1 promoter methylation). Mean HRD score was 13.8 for those with the BRCA1/2 mutation and 6.5 for those with BRCA1/2 wild type (P = 0.0089). Platinum sensitivity was also associated with higher HRD scores; among the 27 BRCA1/2 wild type tumors available, five patients responded. Mean HRD was 12.7 for the responders versus 5.1 for the nonresponders (P = 0.0318).

A total of 69% of 52 patients had p53 mutations, and 17% of 53 patients had PIK3CA mutations; however, neither correlated with ORR (P = 0.73 and P = 0.42, respectively).


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“PAM50 analysis from global gene expression profiling identified 60% (34/55) basal-like tumors, which showed a higher ORR that did not reach significance (24% vs. 10% in basal vs. non-basal; P = 0.29), he said.

All six of the patients who achieved durable responses remain alive and progression free for 3 to 6 years. The longest to survive, at 69 months, is a patient who received cisplatin, had BRCA wild type, and received no adjuvant treatment and has undergone post study surgery, chemotherapy, and radiation therapy. Among these patients, no correlation has been shown with germline BRCA1/2 mutations, basal subtype, p53 mutation, PIK3CA mutation, p63/p73 status, or chemotherapy. Additional studies on these “exceptional responders” are ongoing, including exome sequencing and expression array analysis.

Dr. Isakoff said these results show that “caution is necessary when evaluating biomarkers developed in the pretreatment setting for use in the metastatic setting, such as p63/p73.”

“Randomized studies are required to determine whether mTNBC is uniquely sensitive to platinum chemotherapy compared to other chemotherapy agents,” he concluded, adding that “biomarkers that identify potential ‘exceptional responders’ are urgently needed.”

Reference

  1. Isakoff SJ, He L, Mayer EL et al. Abstract 1020. Presented at: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2014; Chicago, IL.