In a German phase II trial (WSG-TP-II) reported in JAMA Oncology, Gluz et al found that the addition of neoadjuvant paclitaxel monotherapy to trastuzumab/pertuzumab resulted in a higher pathologic complete response (pCR) rate in patients with hormone receptor–positive, HER2-positive early breast cancer compared to treatment with neoadjuvant endocrine therapy plus trastuzumab/pertuzumab.
Study Details
In the open-label multicenter trial, 207 patients were randomly assigned between September 2017 and March 2019 to receive 12 weeks of standard endocrine therapy with an aromatase inhibitor or tamoxifen (n = 100) or paclitaxel at 80 mg/m2 weekly (n = 107) plus trastuzumab (8 mg/kg loading dose followed by 6 mg/kg) and pertuzumab (840 mg loading dose followed by 420 mg) every 21 days. The primary endpoint was pCR (ypT0/is, ypN0).
pCR Rates
pCR rates were 23.7% (95% confidence interval [CI] =15.7%–33.4%) in the endocrine therapy group vs 56.4% (95% CI = 46.2%–66.3%) in the paclitaxel group (odds ratio [OR] = 0.24, 95% CI = 0.12–0.46, P < .001).
Immunohistochemical HER2 score ≥ 3 and HER2-enriched subtype were independent predictors of pCR in both groups. pCR rates in the endocrine therapy group and the paclitaxel group were 26.1% and 60.9% among patients with a HER2 score of ≥ 3 vs 0.0% and 28.6% among those with HER2 scores of < 3. pCR rates in the endocrine therapy group and paclitaxel group were 34.8% and 60.8%, respectively, in patients with a HER2-enriched subtype vs 3.9% and 40.7%, respectively, in patients with a luminal A/B subtype.
KEY POINTS
- Paclitaxel plus trastuzumab/pertuzumab significantly improved pCR rate vs endocrine therapy plus trastuzumab/pertuzumab.
- pCR rates were 56.4% vs 23.7%.
pCR rates were significantly higher in the paclitaxel vs endocrine therapy group in the lower three quartiles of HER2 expression (20.0% vs 0.0%; OR = 6.27, 95% CI = 2.43–16.15), with the improvement in the highest quartile not reaching statistical significance (70.0% vs 55.6%; OR = 1.87, 95% CI = 0.49–7.08).
Adverse Events
During neoadjuvant therapy, totals of 13 vs 10 serious adverse events occurred in the paclitaxel vs endocrine therapy groups. A total of 848 (677 drug-related) nonserious adverse events of any grade occurred in 104 patients in the paclitaxel group vs a total of 348 (239 drug-related) events in 99 patients in the endocrine therapy group. Totals of 30 vs 5 grade 3 or 4 adverse events occurred, with the most common in the paclitaxel group being diarrhea (4%) and infections (3%).
Health-related quality of life scores (using the EORTC-QLQ-C30) remained stable in patients in the endocrine therapy group and decreased significantly in the paclitaxel group at 12 weeks.
The investigators concluded, “The WSG-TP-II randomized clinical trial is, to our knowledge, the first prospective trial comparing two neoadjuvant de-escalation treatments in [hormone receptor–]positive/HER2-positive early breast cancer and demonstrated an excellent pCR rate after 12 weeks of paclitaxel plus trastuzumab and pertuzumab that was clearly superior to the pCR rate after endocrine therapy plus trastuzumab and pertuzumab.”
Oleg Gluz, MD, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by Roche Pharma AG. For full disclosures of the study authors, visit jamanetwork.com.
