Paclitaxel, Carboplatin Regimen Shows Promise in Triple-Negative Breast Cancer

Data from a randomized phase 3 clinical trial recently published in JAMA Oncology show that a platinum-based chemotherapy combination may provide patients with operable triple-negative breast cancer (TNBC) an effective alternative adjuvant treatment option than what is currently in use.

But although results of the randomized, open-label trial demonstrated that the combination of paclitaxel and carboplatin show promise in patients with operable TNBC, the study authors noted that more research is needed for the combination to usurp the current standard of care treatment of anthracycline plus docetaxel.

The addition of carboplatin to a taxane-based chemotherapy regimen with or without an anthracycline-based chemotherapy has been shown, the authors wrote, to increase the proportion of complete responses in TNBC. However, they noted, platinum-based chemotherapy in the adjuvant treatment of patients with TNBC remains controversial.

To assess whether a paclitaxel and carboplatin combination in the adjuvant setting would offer patients with operable TNBC superior benefits compared to a standard regimen of anthracycline and docetaxel, the authors conducted the phase 3 PATTERN trial between July 2011 and April 2016 across nine cancer centers and hospitals in China.

A total of 647 women aged 18 to 70 years with operable TNBC were enrolled onto the trial. Patients were excluded from the trial if they did not have TNBC, presented with metastatic or locally advanced disease, or were receiving preoperative anticancer therapy.

Measuring disease-free survival (DFS), which is the time after primary treatment ends that a patient survives without any signs or symptoms of disease, was the main goal of the study. Other goals included measuring overall survival (OS), distant DFS and relapse-free survival (RFS).

Study participants were randomized to receive either paclitaxel and carboplatin (325 patients) on days 1, 8, and 15 every 28 days for six cycles or cyclophosphamide, epirubicin, and fluorouracil (322 patients) every three weeks for three cycles followed by docetaxel (CEF-T) every three weeks for three cycles.

At a median follow-up of 62 months, 16.1% of the patient population experienced a DFS event. Patients who received carboplatin plus paclitaxel had a longer five-year DFS rate (86.5%) compared with patients who received CEF-T (80.3%). The authors noted that there wasn’t a significant difference in terms of five-year OS between the group that received carboplatin plus paclitaxel (93.4%) and the group that received CEF-T (89.8%).

The data demonstrated that five-year RFS was higher in patients who received the platinum-based combination (91.2%) than those who received CEF-T (84.4%).

“This randomized clinical trial found that compared with the conventional anthracycline and docetaxel regimen, the paclitaxel-plus-carboplatin regimen may be an alternative adjuvant chemotherapy strategy for patients with operable TNBC.”

The authors, however, explained that more research is needed before making the combination the new standard of care for the treatment of this population.

“The results should be considered with caution, as high-level evidence is still lacking to make platinum-based chemotherapy the new standard of care,” the authors wrote. “Moreover, identifying predictive biomarkers is imperative for the selection of appropriate patients for platinum-based regimens in the adjuvant setting.”

The authors acknowledged that there were some limitations to the study.

“First, CEF-T, a preferred regimen when the trial was first designed, is no longer a primary recommendation in the National Comprehensive Cancer Network guidelines,” they wrote. “According to updated data from ECOG 1199, epirubicin and cyclophosphamide followed by weekly paclitaxel (EC-wP) might be the optimal choice for TNBC. However, we lack a head-to-head comparison between CEF-T and EC-wP, and we must point out that our trial predominantly enrolled patients with early-stage TNBC.”

Additionally, the authors noted that the trial only included patients from China and further trials in other ethnic groups are needed.