Neoadjuvant treatment combining SHR-A1811, a novel anti-HER2 antibody-drug conjugate (ADC), with pyrotinib has demonstrated promising antitumor activity and a manageable safety profile in patients with HER2-positive breast cancer. These findings were presented at the 2024 ESMO Congress from the phase 2 MUKDEN 07 trial (NCT05635487).
The study revealed an overall total pathologic complete response (tpCR) rate of 78.6% (95% CI, 59.1%-91.7%) among evaluable patients (n = 29). The breast pathologic complete response (bpCR) was also 78.6% in the overall population, with 89.3% achieving a residual cancer burden (RCB) of 0 or 1. The overall response rate (ORR) across all patients was 89.7%.
MUKDEN 07 Trial Details
The open-label, multi-cohort MUKDEN 07 trial enrolled patients aged 18 to 75 years with stage II or III HER2-positive breast cancer who were treatment-naive and had an ECOG performance status of 0 to 1. The trial included four cohorts with varied doses of SHR-A1811 and pyrotinib.
Cohort A received SHR-A1811 at 4.8 mg/kg intravenously every three weeks plus 240 mg of oral pyrotinib daily for 6 cycles. Cohort B received SHR-A1811 at 5.6 mg/kg every three weeks plus 240 mg of pyrotinib daily. Cohort C received SHR-A1811 at 4.8 mg/kg with a reduced pyrotinib dose of 160 mg daily, and cohort D received SHR-A1811 at 4.0 mg/kg plus 240 mg of pyrotinib daily. Data were cut off on May 6, 2024.
The primary objective was tpCR rate, with secondary endpoints including bpCR rate, RCB rate, ORR, and safety. The median age of patients was 55 years (range, 38-61), with a majority having hormone receptor (HR)-positive disease (62.1%) and HER2 expression of immunohistochemistry 3+ (72.4%).
Efficacy and Safety Outcomes
Analysis by HR status showed slightly higher tpCR rates in HR-negative patients (81.8%) compared to HR-positive patients (76.5%). Four patients experienced dose-limiting toxicities (DLTs): diarrhea in cohorts A and C, neutropenia in cohort B, and thrombocytopenia in cohort D.
The most common treatment-related adverse effects (≥20% of patients) included diarrhea (any-grade, 100%; grade ≥3, 51.7%), anemia (93.1%; 20.7%), nausea (93.1%; 0%), vomiting (82.8%; 0%), neutropenia (79.3%; 62.1%), increased alanine aminotransferase levels (79.3%; 6.9%), asthenia (79.3%; 0%), leukopenia (72.4%; 44.8%), and hypokalemia (62.1%; 24.1%).
According to lead study author Dr. Caigang Liu, an oncologist at Shengjing Hospital of China Medical University, "SHR-A1811 combined with pyrotinib as neoadjuvant therapy for HER2-positive breast cancer may lead to promising antitumor efficacy with a manageable toxicity profile."
