Pyrotinib plus nab-paclitaxel as adjuvant therapy for patients with N0/N1mi, HER2-positive early-stage breast cancer: 3-year iDFS results of the phase II PHAEDRA trial.

533 Background: While dual anti-HER2 therapy is standard in the adjuvant setting for HER2-positive early breast cancer, treatment de-escalation is an attractive strategy for patients with low-risk disease. Previous studies (e.g., APT, ATEMPT) of adjuvant trastuzumab plus chemotherapy or T-DM1 monotherapy in this population reported 3-year invasive disease-free survival (iDFS) rates of 93.4%-98.7%. Pyrotinib, an irreversible pan-HER2 tyrosine kinase inhibitor, is effective in HER2-positive breast cancer; however, data supporting its use in the adjuvant setting for low-risk disease are limited. This study evaluated the efficacy and safety of adjuvant pyrotinib plus nab-paclitaxel in this population. Methods: This multicenter, single-arm, phase II trial enrolled women aged 18-75 with primary tumor size ≤3 cm and node-negative (N0) or micrometastases (N1mi), histologically confirmed HER2-positive early breast cancer. Patients received nab-paclitaxel (260 mg/m² IV, q3w) plus pyrotinib (400 mg PO, qd) for 12 weeks (4 cycles), followed by pyrotinib monotherapy (400 mg, qd) for one year. The primary endpoint was iDFS. Secondary endpoint was adverse events (AEs) graded by CTCAE v5.0. Results: From January 8, 2021, to September 21, 2023, 263 patients were enrolled and received treatment. Median age was 51 years; 60.8% (160/263) were hormone receptor-positive, and 97.7% (257/263) were node-negative. At the data cutoff (December 30, 2025), with a median follow-up of 36.2 months, 9 iDFS events were observed. The estimated 3-year iDFS rate was 96.8% (95% CI 93.4-98.5). One death occurred and overall survival data were immature. The most common grade ≥3 treatment-related AEs were diarrhea (50.6%), neutropenia (14.4%), and decreased white blood cell count (14.4%). No serious AEs were reported. Treatment interruption, dose reduction, and discontinuation due to AEs occurred in 12.2%, 3.4%, and 1.5% of patients, respectively. Conclusions: Adjuvant pyrotinib combined with nab-paclitaxel showed promising 3-year iDFS and a manageable safety profile in patients with low-risk, HER2-positive early breast cancer. This regimen represents a potential oral de-escalation strategy for this population. Clinical trial information: NCT 04659499 . Efficacy outcomes. Efficacy outcomes Pyrotinib + nab-Paclitaxel（n=263） Events, n(%) 9 (3.4) 24 months 36 months 48 months iDFS rate, (95% CI) 98.77(96.24, 99.60) 96.83(93.42, 98.49) 93.17(85.03, 96.96) DDFS rate, (95% CI) 99.18(96.76, 99.79) 98.77(96.23, 99.60) 95.03(86.00, 98.29) LRFS rate, (95% CI) 99.18(96.75, 99.79) 98.18(95.18, 99.32) 94.47(85.76, 97.92) iDFS: invasive disease-free survival; DDFS: distant disease-free survival; LRFS: locoregional recurrence-free survival.