medwireNews: For patients with newly diagnosed human epidermal growth factor receptor 2 (HER2)-negative breast cancer, the ETNA trial results suggest that substituting neoadjuvant solvent-based paclitaxel with nab-paclitaxel before anthracycline-based chemotherapy does not improve the rate of pathological complete remission (pCR).
The phase III, open-label study's primary endpoint – defined as absence of invasive cells in both the breast and axillary nodes by time of surgery – was met by 22.5% of the 346 patients randomly assigned to receive four cycles of nab-paclitaxel 125 mg/m
This was not significantly higher than the 18.6% pCR rate achieved by the 349 patients whose neoadjuvant regimen consisted of paclitaxel 90 mg/m2 given on the same schedule, report Luca Gianni, from the San Raffaele Scientific Institute in Milan, Italy, and co-investigators.
Furthermore, nab-paclitaxel was associated with a higher rate of serious adverse events, affecting 16.0% of patients versus 11.3% of their paclitaxel-treated counterparts. And grade 3 or worse peripheral neuropathy (4.5 vs 1.8%) and neutropenia (30.6 vs 19.7%) were significantly more common with nab-paclitaxel.
However, the researchers note that “the different tolerability did not affect the overall drug delivery”, with dose reductions required for 11.0% of the nab-paclitaxel and 8.4% of the paclitaxel groups.
Multivariate analysis, adjusting for patient age, tumour stage and subtype, and treatment indicated that tumour subtype was the most significant factor affecting treatment outcome, with a hazard ratio of 4.85 for pCR that favoured triple-negative patients versus those with other subtypes.
“The data do not show a different outcome of paclitaxel vs nab-paclitaxel in triple-negative or in [hormone receptor]-positive tumors selected to approximate the luminal-B subtype and do not support direct substitution of paclitaxel with nab-paclitaxel at the doses and schedule adopted in the ETNA trial”, Luca Gianni et al therefore conclude.
But they add: “The extensive biobanking performed in the trial will allow for translational studies and better interpretation of the clinical findings.”
In a linked editorial, Joseph Sparano, from Montefiore Medical Center in New York, USA, notes the ETNA trial results are in contrast to those of the GeparSepto (GBG69) trial which showed a small but significant improvement in pCR with a different dosage of nab-paclitaxel versus paclitaxel before an anthracycline plus cyclophosphamide regimen. These HER2-positive patients also received concurrent trastuzumab–pertuzumab.
While acknowledging that nab-paclitaxel is “appealing” because of its shorter infusion time and avoidance of corticosteroid premedication, he believes the higher rates of grade 3–4 neuropathy with nab-paclitaxel in both trials and greater cost, as well as comparable rates of breast conservation and need for axillary surgery is “insufficient evidence” for its use in triple-negative breast cancer.
“On the other hand, for patients who develop a hypersensitivity reaction to solvent-based paclitaxel or docetaxel, or those who have contraindications to corticosteroids, nab-paclitaxel offers an effective
option in those who would otherwise not be able to receive taxane therapy,” the editorialist says.
Gianni L, Mansutti M, Anton A, et al. Comparing neoadjuvant nab-paclitaxel vs paclitaxel both followed by anthracycline regimens in women with ERBB2/HER2-negative breast cancer – the Evaluating Treatment With Neoadjuvant Abraxane (ETNA) trial. A randomized phase 3 clinical trial. JAMA Oncol; Advance online publication 11 January 2018. doi:10.1001/jamaoncol.2017.4612
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group