TNT Study for Triple-Negative or BRCA1/2 Breast Cancer

The phase III TNT trial randomized 376 patients with triple-negative breast cancer (TNBC) or BRCA1/2 mutation positive metastatic breast cancer to first-line treatment with docetaxel or carboplatin. In the full population, the results did not demonstrate a significant difference between the two agents, states Debu Tripathy, MD, although patients with BRCA1/2 mutations who received carboplatin achieved a greater response and longer progression-free survival compared with docetaxel.

In those with BRCA1/2 breast cancer, the objective response rate (ORR) with carboplatin was 68.0% compared with 33.3% for docetaxel (P = .03). In this same population, carboplatin showed a 6.8-month progression-free survival compared with 4.8 months with docetaxel. However, patients with homologous recombination deficiency (HRD) experienced similar outcomes between the docetaxel and carboplatin arm. In the HRD high arm, the ORR with carboplatin was 38.2% versus 42.6% with docetaxel (P = .82).

The TNT data did not show that HRD, which is hypothesized to confer sensitivity to platinum agents, made a difference in terms of outcomes, notes Joyce O’Shaughnessy, MD. Earlier administration of the ACT regimen (doxorubicin and cyclophosphamide followed by docetaxel) in the adjuvant or neoadjuvant setting may have eliminated cells with HRD, resulting in a disease without HRD at the time of recurrence, O’Shaughnessy postulates.

There aren’t enough data at present to use HRD testing to select patients for carboplatin treatment in TNBC, comments Edith Perez, MD. For the overall group of patients, physicians can use either docetaxel or carboplatin, adds Perez.