The following is a summary of “Nab-paclitaxel weekly versus dose-dense solvent-based paclitaxel followed by dose-dense epirubicin plus cyclophosphamide in high-risk HR+/HER2− early breast cancer: results from the neoadjuvant part of the WSG-ADAPT-HR+/HER2− trial,” published in the June 2023 issue of the Oncology by Gluz et al.

In neoadjuvant trials for high-risk hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2) early breast cancer (EBC), nanoparticle albumin-bound (nab)-paclitaxel demonstrated promising efficacy compared to solvent-based (sb)-paclitaxel; however, optimal patient and therapy selection remains an area of active investigation. Oncotype DX® recurrence score (RS) and endocrine therapy (ET) response (low post-endocrine Ki67) for therapy selection are investigated. High-risk HR+/HER2 EBC patients were randomized to (neo)adjuvant 4× sb-paclitaxel 175 mg/m2 q2w or 8× nab-paclitaxel 125 mg/m2 q1w, followed by 4× epirubicin + cyclophosphamide (90 mg + 600 mg) q2w, in the WSG-ADAPT trial (NCT01779206). Patients with cN2-3 or (G3, baseline Ki67 40%, and tumor size >1 cm) could be enrolled without RS and ET testing. 

Using statistical mediation and moderation models, the associations of important factors with the complete pathological response (pCR) (primary) and survival (secondary) endpoints were analyzed. 864 patients were treated with nab-paclitaxel (n = 437) or sb-paclitaxel (n = 427); nab-paclitaxel was preferable for pCR (20.8% vs 12.9%, P = 0.002). pCR was higher for RS >25 vs RS ≤25 (16.0% vs 8.4%, P = 0.021) and ET non-response vs ET response (15.1% vs 6.0%, P = 0.027); no characteristics predicted the relative efficacy of nab-paclitaxel vs sb-paclitaxel [dDFS; hazard ratio 0.42, 95% CI: 0.20-0.91, P = 0.024]. Patients with pCR had prolonged distant disease-free survival. 

Despite the favorable prognostic association of RS >25 relatives to RS≤ 25 with pCR (odds ratio 3.11, 95% CI 1.71-5.63, P≤0.001), higher RS was negatively associated with dDFS (hazard ratio 1.03, 95% CI 1.01-1.10, P = 0.010). Regarding pCR, neoadjuvant nab-paclitaxel q1w appears superior to sb-paclitaxel q2w in high-risk HR+/HER2 EBC. Combining RS and ET response assessment seems to select patients with excellent pCR rates. In patients with pCR, the disadvantage of a higher RS for dDFS is diminished. These are the first findings from a large randomized neoadjuvant trial supporting the use of RS to select patients for neoadjuvant chemotherapy in HR+/HER2 EBC with elevated risk.

Source: sciencedirect.com/science/article/pii/S0923753423001369