ESMO Focus | The Latest Research Findings of Doxorubicin Unveiled

Recently, the annual meeting of the European Society for Medical Oncology (ESMO) is being held in Paris, France. The ESMO Congress is the most prestigious and influential oncology conference in Europe and a platform for publishing the latest clinical research findings in oncology.

The results of a collaborative study between CSPC and Professor Liu Qiang's team from Sun Yat-sen Memorial Hospital, Sun Yat-sen University, were presented in a poster session at the 2022 ESMO Congress. It is a Phase II single-arm clinical study of pegylated liposomal doxorubicin (PLD) + cyclophosphamide (C) in combination with trastuzumab (H) and Pertuzumab (P) for the neoadjuvant treatment of HER2-positive breast cancer.

Background

For neoadjuvant treatment of HER2 (human epidermal growth factor receptor 2)-positive breast cancer, the earlier the HER2-targeted drugs are used, the more likely the tumor shrinkage effect will be achieved as soon as possible. However, due to cardiotoxicity, the concomitant use of trastuzumab and traditional anthracyclines is usually avoided in clinical practice. Pegylated liposomal doxorubicin (PLD) is significantly less cardiotoxic than doxorubicin and is safe to use in combination with trastuzumab in patients with advanced breast cancer. This prospective study was designed to evaluate the efficacy and safety of PLD in combination with trastuzumab and pertuzumab in the neoadjuvant treatment of HER2-positive breast cancer.

Methodology

This study is a single-arm, single-center, Phase II clinical study. The study planned to include 78 patients with non-metastatic HER2-positive breast cancer receiving 4 cycles of PLD (30-35 mg/m2) + cyclophosphamide + trastuzumab + Pertuzumab sequential to 4 cycles of paclitaxel + trastuzumab + Pertuzumab neoadjuvant therapy. The primary study endpoint was the rate of pathological complete remission (pCR, ypT0/isN0), and the secondary study endpoints were the objective response rate (ORR) and safety at the completion of the first 4 cycles of treatment.

Findings

As of July 25, 2022, 78 patients were enrolled, of which 64 had pathological results. See Table 1 for the baseline characteristics of patients.

Table 1: Baseline Characteristics

Efficacy: the pCR rate was 59.4% (38/64), while the ORR at the completion of the first 4 cycles of treatment was 68.8%. See Table 2 for the data for pCR rate.

Table 2: pCR rate

The most common Grade 3-4 adverse events (AEs) were white blood cell count decreased (21.9%), lymphocyte count decreased (21.9%), and neutrophil count decreased (18.8%). In terms of cardiac safety, the asymptomatic left ventricular ejection fraction (LVEF) decreased by ≥10% from baseline in 6 patients. However, the LVEF was higher than 55%. See Table 3 for the data of Grade 3-4 AEs.

Table 3: Grade 3-4 Adverse Events (AEs)

Conclusions

Preliminary results showed that PLD in combination with cyclophosphamide and trastuzumab and pertuzumab sequential to taxanes in combination with trastuzumab and pertuzumab neoadjuvant therapy for HER2-positive breast cancer is safe and has enormous potential in efficacy.