Dr. Luca Gianni
“The primary endpoint of pathological complete response was 18.1% with paclitaxel and 22.5% for nab-paclitaxel,” said Luca Gianni, MD, of San Raffaele Scientific Institute, in Milan, who presented the study. The crude difference was 3.9% for an odds ratio of 0.77 (0.52, 1.13) and a nonsignificant difference with p-value of 0.1858.
ETNA Study Data
ETNA was a randomized phase III trial designed for women HER2-negative or operable or locally advanced unilateral breast cancer.
A total of 695 patients enrolled on the study and were distinguished as having triple-negative or luminal B-like breast cancer. The characteristics were well-balanced between the two treatment arms regarding disease stage (approximately 25% had locally advanced tumors), tumor subtype (54% of patients had with luminal B-high disease; 31.5% of patients had triple-negative disease), median age (50 years), T stage, and nodal status. “From the size of the tumor and the clinical status, you can derive the sense that it was a high-risk population,” Dr. Gianni said.
Patients were randomly assigned to receive either paclitaxel 90 mg/m2 weekly for 3 weeks every 4 weeks for four cycles followed by an anthracycline regimen cycle every 3 weeks for 4 cycles (349 patients) or nab-paclitaxel at 125 mg/m2 weekly for 3 weeks every 4 weeks for four cycles followed by anthracycline for four cycles (346 patients). Following surgery, patients with HR-positive tumors received endocrine therapy.
The primary endpoint, which looked to identify a 10% improvement in the pCR (absence of invasive cells in the breast and nodes) between paclitaxel and nab-paclitaxel—was not met. In subgroup analysis—which included tumor subtype, stage, and age—the pCR rate tended to be higher in the nab-paclitaxel arm. “The only variable that was statistically associated with a higher probability of achieving a pCR was tumor subtype, with triple-negative tumors more likely to receive a pCR than luminal B-like tumors,” Dr. Gianni said.
Dr. Stephen K. L. Chia
“ETNA had a standard backbone with the anthracycline after the taxane with slight difference from the GeparSepto study,” said Stephen K. L. Chia, MD, FRCPC, of the British Columbia Cancer Agency. Those differences included the paclitaxel dose (90 mg/m2 vs. 80 mg/2), the anthracycline dose, and dosing schedule.
“In the GeparSepto study,1 they were able to show a statistically significant improvement in pCR in breast and nodes,” Dr. Chia said. That study found a pCR of 38% in the nab-paclitaxel group compared with 29% in the paclitaxel-treated arm.
What may explain the differences between ETNA and GeparSepto?
“One thing may be extensive subgroup extrapolation,” Dr. Chia said. “There are also differences in the trial population in the biology of the patients’ tumors and heterogeneity in the pathology assessment for pCR.”
However, he suggests that what is needed is a biomarker beyond triple-negative breast cancer or SPARC expression. Moving forward for future neoadjuvant strategies, Dr. Chia also suggested striving for universally agreed upon standard chemotherapy backbones.
– Alice McCarthy