Extended Adjuvant Pyrotinib Shows Promising Efficacy After Trastuzumab-Based Therapy in HER2+ Breast Cancer

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Extended treatment with pyrotinib in the adjuvant setting following trastuzumab (Herceptin)-based adjuvant therapy displayed efficacy in patients with high-risk, HER2-positive early or locally advanced breast cancer, according to data from the phase 2 PERSIST trial (NCT05880927).

At a median follow-up of 24 months (IQR, 18.0-34.0), the 2-year invasive disease-free survival (iDFS) rate was 94.59% (95% CI, 88.97%-97.38%) in the overall population (n = 141). Additionally, patients who completed 6 (n = 31) or 12 months (n = 92) of pyrotinib treatment achieved 2-year iDFS rates of 90.32% (95% CI, 72.93%-96.77%) and 94.90% (95% CI, 86.97%-98.06%), respectively.

“Approximately one-third of patients with HER2-positive breast cancer experienced recurrence within 10 years after receiving 1 year of adjuvant trastuzumab,” the study authors wrote. “[Data from] the [phase 3] ExteNET study [NCT00878709] showed that 1 year of extended adjuvant neratinib [Nerlynx] after trastuzumab-based adjuvant therapy could reduce iDFS events compared with placebo. This study investigated the efficacy and safety of pyrotinib, an irreversible pan-HER receptor TKI, after trastuzumab-based adjuvant therapy in patients with high-risk, HER2-positive early or locally advanced breast cancer.”

PERSIST was an investigator-initiated, exploratory trial that enrolled patients 18 to 75 years old at 23 sites in China. Eligible patients needed to have high-risk, HER2-postitive (immunohistochemistry 3+ or 2+ with gene amplification by fluorescence in situ hybridization) early or locally advanced invasive breast cancer, have completed 1 year of adjuvant therapy with either trastuzumab or trastuzumab plus pertuzumab (Perjeta) within 6 months of enrollment, have an ECOG performance status of 0 or 1, have known hormone receptor (HR) status, and have adequate bone marrow, hepatic, renal, and cardiac function.

Patients received oral pyrotinib at a dose of 400 mg once daily within 6 months of the completion of adjuvant trastuzumab-based therapy. The investigators recommended concurrent adjuvant endocrine therapy for patients with HR-positive disease. Treatment continued for 1 year unless intolerable adverse effects (AEs), disease recurrence, death, or withdrawal of consent occurred.

The primary end point was iDFS rate at 2 years. Safety represented the secondary end point.

At baseline, the median age was 50 years (range, 25-72). Most patients had negative HR status (54.6%), a Ki-67 score of at least 20% (84.4%), and received adjuvant trastuzumab monotherapy (65.2%). Patients had stage T1 (30.5%), T2 (58.9%), T3 (7.8%), T4 (1.4%), or an undeterminable (1.4%) stage disease. In terms of nodal status, patients were node negative (24.1%), had 1 to 3 positive nodes (34.8%), or more than 3 positive nodes (41.1%).

Additional findings from PERSIST revealed that patients with HR-positive disease (n = 64) experienced a 2-year iDFS rate of 96.74% (95% CI, 87.57%-99.18%). Patients with HR-negative breast cancer (n = 77) achieved a 2-year iDFS rate of 92.77% (95% CI, 83.48%-96.93%). Patients with lymph node–negative (n = 34) or –positive (n = 107) disease experienced 2-year iDFS rates of 96.88% (95% CI, 79.82%-99.55%) and 93.85% (95% CI, 86.81%-97.20%), respectively. The 2-year iDFS rates were 97.30% (95% CI, 82.32%-99.61%) in patients who received adjuvant trastuzumab plus pertuzumab (n = 49) and 93.48% (95% CI, 86.06%-97.02%) in patients who received adjuvant trastuzumab monotherapy (n = 92).

In terms of safety, the most common any-grade treatment-emergent AEs (TEAEs) included diarrhea (79.4%), fatigue (36.9%), decreased lymphocyte count (36.9%), nausea (33.3%), and hand-foot syndrome (33.3%). Grade 3 TEAEs consisted of diarrhea (30.5%) and hand-foot syndrome (0.7%).

Eleven patients were forced to discontinue treatment due to grade 3 diarrhea (n = 8), grade 3 hand-foot syndrome (n = 1), and intolerance to therapy (n = 2). Dose reductions due to AEs were reported in 16 patients.

“Our study suggests the potential of extended adjuvant pyrotinib in patients with high-risk HER2-positive early or locally advanced breast cancer after trastuzumab-based adjuvant therapy,” the study authors wrote in their conclusion. “Follow-up is ongoing to determine the long-term benefit of extended adjuvant pyrotinib.”

Reference

Cao F, Ma Z, Wu Z, et al. Pyrotinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (PERSIST): a multicenter phase II trial. Elife. 2025;13:RP101724. doi:10.7554/eLife.101724