SABCS 2014 - Triple negative breast cancer (TNBC)

Biomarkers
Myriad-genetics has sponsored two trials on biomarkers in TNBC. The first one in metastatic TNBC comparing Carboplatin to Docetaxel in TNBC (TNT trial). The study showed no difference between Carboplatin and Docetaxel. But, in when the germ-line BRCA+ mTNBC patients were analyzed, the results became quite interesting. The response rate in BRCA+ mTNBC was 68% vs 33% in favor of Carboplatin. The non-basal TNBC (by PAM50) had a remarkable response to Docetaxel (but, it was a small subgroup of patients). The company has also created a genetic test called HRD (Homologous Recombination Deficiency) test to assess the integrity of the DNA repair mechanism in TNBC patients. In a companion trial, patients with early breast cancer had a 52% response rate to platinum if they tested positive to HRD, and only 10% if the results were negative.

Geparsepto: Nab-Paclitaxel in neoadjuvant BC
The germans presented they large Geparsepto trial with about 1200 patients comparing neoadjuvant Paclitaxel followed by EC to nab-Paclitaxel (150 mg/wk) followed by EC. The endpoint was pathologic complete response (pCR). Nab-paclitaxel arm exhibited higher neuropathy and diarrhea. The study met its primary endpoint with an increase in the pCR from 28% to 39% (p=0.001). The results were impressive in the TNBC group with pCR of 48% (25% with the conventional paclitaxel).

Pembrolizumab in TNBC
A phase 1b trial reported by Rita Nanda with Pembrolizumab 10 mg/kg IV q2wk in 32 heavily pretreated PD-L1+ (by IHC) TNBC patients. There were 5 responses in the 27 evaluable patients (ORR: 18.5%), with 1 CR. The median duration of response was >40 weeks (in responding patients), and 1.9 mo (in the others). Treatment was well tolerated, one patient with rapidly progressive metastatic disease died of disseminated intravascular coagulation.