Study Shows Paclitaxel, Carboplatin Effective Against Triple-Negative Breast Cancer

A recent phase 3 trial of a platinum-based chemotherapy in patients with triple-negative breast cancer (TNBC) with operable disease showed promise but researchers cautioned that additional research is needed.

The Adjuvant Platinum and Taxane in Triple-Negative Breast Cancer (PATTERN) trial investigated the combination of paclitaxel and carboplatin (PCb) in TNBC vs the standard-of-care anthracycline plus docetaxel and found it was effective, according to the randomized, open-label, multicenter study results published in JAMA Oncology.

In particular, disease- (DFS) and relapse-free survival (RFS) were both longer in the trial group (n = 325), which received 6 cycles of PCb, compared with the usual-care group (n = 322), which first received 3 cycles of cyclophosphamide, epirubicin, and fluorouracil, then 3 cycles of docetaxel (Taxotere) (CEF-T). All of the women had pathologically confirmed regional node-positive or -negative disease with tumors larger than 10 mm.

With a primary endpoint of DFS and secondary endpoints of overall survival (OS), distant DFS, RFS, DFS in patients with germline variants in BRCA1 and BRCA2 or homologous recombination repair (HRR)-related genes, and toxicity, the phase 3 randomized trial enrolled its patients between July 1, 2011, and April 30, 2016, before analyzing their data from December 1, 2019, and January 31, 2020. The patients came from 9 cancer centers and hospitals in China, and they had a median (interquartile range [IQR]) age of 51 (IQR, 44-57) years.

Patients were excluded if they had metastatic or locally advanced disease, did not have TNBC, or had previous preoperative anticancer therapy (chemotherapy and radiotherapy). They also had to have adequate hematologic function, adequate hepatic/renal function, and normal cardiac function.

“Both BRCA-associated breast cancer and sporadic TNBC exhibit characteristics consistent with abnormal DNA repair and genome-wide instability, which supports the use of DNA-damaging compounds, such as platinum derivatives,” the authors noted. However, their use as adjuvant treatment among patients with TNBC remains controversial, which is why they took up their investigation.

The trial group received paclitaxel 80 mg/m2 and carboplatin (area under the curve, 2) on days 1, 8, and 15 every 28 days for the 6 cycles, while the usual-care group got cyclophosphamide 500 mg/m2, epirubicin 100 mg/m2, and fluorouracil 500 mg/m2 every 3 weeks for 3 cycles before treatment with docetaxel 100 mg/m2 for another 3 cycles, each 3 weeks apart.

Results show that 5-year DFS was longer among the PCb recipients than those who got CEF-T: 86.5% vs 80.3% (HR, 0.65; 95% CI, 0.44-0.96; P = .03). However, OS did not differ significantly, at 93.4% vs 89.8% (HR, 0.71; 95% CI, 0.42-1.22; P = .22), respectively. Overall, 16.1% of all study participants experienced DFS events.

In addition, 2 subgroup analyses produced the following findings:

• Patients with a BCRA1 or BRCA2 variant who received PCb had a 56% lower risk of death (HR, 0.44; 95% CI, 0.15-1.31; P = .14).
• Patients with an HRR variant who received PCb had a 61% lower risk of death (HR, 0.39; 95% CI, 0.15-0.99; P = .04).

Nevertheless, these findings were from an exploratory analysis and were hypothesis-generating, so the authors call for additional investigation.

The remaining findings of RFS and distant DFS show the superiority of PCb vs CEF-T:

1. RFS: 91.2% vs 84.4% (HR, 0.54, 95% CI, 0.34-0.88; P = .01)
2. Distant DFS: 92.6% vs 87.9% (HR, 0.59; 95% CI, 0.35-0.999; P = .05)

Adverse effects did occur, and they were mostly hematological.

“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 concluded. “However, the results should be considered with caution, as high-level evidence is still lacking to make platinum-based chemotherapy the new standard of care.”

Progress can be made, they suggest, through the identification of predictive biomarkers to aid in selecting the patients for whom adjuvant platinum-based treatment would be most appropriate.

Reference

Yu K-D, Ye F-G, He M, et al. Effect of adjuvant paclitaxel and carboplatin on survival in women with triple-negative breast cancer: a phase 3 randomized clinical trial. JAMA Oncol. Published online August 13, 2017. doi:10.1001/jamaoncol.2020.2965