Pyrotinib plus a new antibody-drug conjugate in HER+ breast cancer

A phase 2b trial recently published on Nature Communications shows a significant clinical benefit with the antibody-drug conjugate ARX788 and the tyrosine kinase inhibitor pyrotinib as a neoadjuvant treatment in patients with early or locally advanced HER2-positive breast cancer.

Pyrotinib is an irreversible tyrosine kinase inhibitor targeting HER1, HER2, and HER4; ARX788 is an antibody-drug conjugate consisting of a trastuzumab-based antibody conjugated to two tubulin inhibitors; clinical studies have demonstrated the efficacy and safety of ARX788 in HER2-positive metastatic breast cancer. The MUKDEN 06 trial, a multicentre, randomised, phase 2b study, compared the anti-HER2 antibody-drug conjugate ARX788 plus pyrotinib with the standard neoadjuvant regimen of docetaxel, carboplatin, trastuzumab, and pertuzumab in 152 patients. Results show a pathological complete response achieved in 70.6% of patients receiving ARX788 plus pyrotinib, compared to 51.5% in the standard neoadjuvant group, with a significant absolute difference of 19.1%. The most common grade 3–4 adverse events were diarrhea and hepatic dysfunction in the ARX788 plus pyrotinib group, and fatigue, nausea and anorexia in the standard neoadjuvant group. Interstitial lung disease/pneumonitis and ocular events were observed with ARX788 plus pyrotinib, indicating a distinct safety profile. «While this combination demonstrated a distinct safety profile requiring further refinement, it represents a therapeutic strategy for patients who may not respond optimally to conventional neoadjuvant regimens. Ongoing research into biomarker-driven patient selection and toxicity management will be essential to optimizing the clinical utility of antibody-drug conjugate – tyrosine kinase inhibitors combinations in HER2-positive breast cancer», authors conclude.