Substituting Nab-paclitaxel in Anthracycline Regimen Did Not Significantly Improve pCR in HER2-negative Breast Cancer

CHICAGO — Replacing paclitaxel with nab-paclitaxel in an anthracycline regimen failed to significantly improve the pathologic complete response rate in patients with HER2-negative breast cancer, according to research presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

“Sequential anthracycline and taxane regimens are a reference adjuvant therapy for high-risk breast cancer,” said lead investigator Luca Gianni, MD, medical oncologist at San Raffaele Scientific Institute in Milano, Italy. “In the sequence, weekly paclitaxel is superior to a taxane every 3 weeks.”

Neoadjuvant chemotherapy regimens with a taxane followed by an anthracycline doubled pathologic complete response rates, and the reverse sequence is at least equally effective. Because nab-paclitaxel, an albumin-bound nanoparticle formulation of paclitaxel that allows for safe infusion with premedication, is associated with a significantly higher pathologic complete response rate compared with paclitaxel in the neoadjuvant setting,² investigators decided to compare outcomes after neoadjuvant nab-paclitaxel with paclitaxel followed by an anthracycline-based regimen in a phase 3 trial.

In the multicenter, open-label ETNA trial, researchers enrolled 695 patients with centrally confirmed HER2-negative breast cancer and randomly assigned them to receive paclitaxel 90 mg/m² or nab-paclitaxel 125 mg/m² on weeks 1, 2, and 3, followed by a 1-week rest, for 4 cycles. All patients then received an anthracycline-based regimen per investigator choice.

Results showed that the pathologic complete response rate was 18.6% (95% CI, 14.7-23.1) with paclitaxel vs 22.5% (95% CI, 18.2-27.3) with nab-paclitaxel (OR, 0.77; 95% CI, 0.52-1.13; P=.1858).

“The improved rate of pathologic complete response rate after nab-paclitaxel did not reach statistical significance,” Dr Gianni noted.

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In addition, multivariate analyses demonstrated that tumor subtype was most significantly associated with treatment outcome (OR, 4.85).

In terms of safety, the protein-bound paclitaxel was associated with a higher overall rate of grade 3 or worse peripheral neuropathy, neutropenia, fatigue, and vomiting compared with paclitaxel.

Dr Gianni concluded that extensive collection and banking of tumor (>90%) and blood were performed and translational studies might provide clues for informative correlations with available clinical findings.

Reference

1. Gianni L, Mansutti M, Anton A, et al. ETNA (Evaluating Treatment with Neoadjuvant Abraxane) randomized phase III study comparing neoadjuvant nab-paclitaxel (nab-P) versus paclitaxel (P) both followed by anthracycline regimens in women with HER2-negative high-risk breast cancer: A MICHELANGO study. J Clin Oncol. 2016; 34 (suppl; abstr 502).
2. Untch M, Jackisch C, Schneeweiss A, et al. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. 2016;17(3):345-56. doi:10.1016/S1470-2045(15)00542-2.