△ At ESMO 2024, Cristina Saura presented clinical trial data from the ICARUS-BREAST01 study in the metastatic breast cancer session.
New positive results in advanced or metastatic breast cancer research support the use of ADCs for a broader range of patients.
Antibody-drug conjugates have expanded treatment options for patients with unresectable locally advanced or metastatic breast cancer, providing new options for those who have exhausted other treatments. Studies presented at the 2024 European Society for Medical Oncology (ESMO) Congress (September 13-17, Barcelona) aimed to expand the current use of ADCs to a wider patient population and explore novel ADCs in advanced or metastatic breast cancer, shedding light on targeting HER2 and HER3 to improve patient outcomes.
The latest primary results from the open-label phase IIIb/IV DESTINY-Breast12 study (LBA18) showed significant and durable efficacy of T-DXd in 504 patients with HER2-positive metastatic breast cancer, including those with brain metastases. Among patients with brain metastases (n=263), the 12-month progression-free survival (PFS) rate was 61.6%, with a 12-month central nervous system (CNS) PFS rate of 58.9%. Notably, PFS rates were similar for both stable brain metastases (57.8%) and active brain metastases (60.1%). All 504 patients in this open-label trial had disease progression following ≤2 prior lines of treatment.
Dr. Philippe Aftimos of the Institut Jules Bordet, commented on these results, saying, “These outcomes have been highly anticipated, given the high incidence of brain metastases in HER2-positive metastatic breast cancer. Until recently, most patients required radiotherapy, which carries significant toxicity risks.” He added, “Initially, there were reservations about using T-DXd for untreated brain metastases due to concerns about its large molecular weight and limited blood-brain barrier penetration. However, DESTINY-Breast12 results indicate positive outcomes for brain metastasis patients, suggesting that systemic strategies may effectively treat advanced breast cancer with brain metastases without additional local therapies.”
At the conference, researchers from France shared results from the phase II single-arm ICARUS-BREAST01 study, which evaluated the efficacy of the novel anti-HER3 antibody-drug conjugate, patritumab deruxtecan, in patients with HR+/HER2- unresectable locally advanced or metastatic breast cancer who had disease progression following CDK4/6 inhibitors and first-line chemotherapy (Abstract 340O). At data cutoff, 99 patients had been treated, with a median follow-up of 15.3 months, achieving a confirmed objective response rate of 53.5% and a median PFS of 9.4 months. Dr. Aftimos noted, “While the significance of HER3 as a target is still being understood, HER3 expression has been linked to poor prognosis.” He highlighted that patritumab deruxtecan’s efficacy appears promising, with around 50.1% of patients experiencing ≥grade 3 treatment-related adverse events, the most common being fatigue, nausea, and diarrhea. “We have experience managing such adverse events, and based on current data, patritumab deruxtecan should be tolerable in clinical settings,” Dr. Aftimos stated.
Considering recent findings from the DESTINY-Breast06 trial in HR+/HER2-low or ultra-low metastatic breast cancer (90.4% of patients had received prior CDK4/6 therapy) [J Clin Oncol. 2024;42(Suppl)], Dr. Aftimos remarked, “These encouraging early results suggest that patritumab deruxtecan could become a future treatment option for HR+/HER2- advanced breast cancer patients who have failed CDK4/6 inhibitors. We eagerly await further clinical data.”
Dr. Aftimos emphasized the need for more data and acknowledged existing challenges in integrating ADCs into clinical practice. “While ADCs are already approved for metastatic breast cancer, and ongoing trials in earlier stages continue to yield positive results, we need to establish the optimal way to introduce new ADCs into curative treatment regimens while managing their side effects effectively. Additionally, the multiple ADC options in breast cancer raise questions about the treatment sequence.” Currently, two new ADCs have been approved for advanced/metastatic breast cancer: T-DXd for HER2-positive and HER2-low expression breast cancer patients, and sacituzumab govitecan for heavily pretreated triple-negative breast cancer and HR+/HER2- breast cancer.
Dr. Aftimos highlighted the need for a better understanding of biomarkers and their correlation with outcomes to extend ADC therapy access to a broader patient population. He noted the promising results in HER2 ultra-low expression patients observed in the DESTINY-Breast06 trial and called for more data on HER3 targeting. “I am pleased to see emerging evidence on new ADCs for advanced and metastatic breast cancer. Moving forward, more research is needed to explore the role of ADCs in earlier treatment lines. Ongoing ADC research offers great hope for the future, potentially enabling more personalized and effective treatment plans to improve patient outcomes,” Dr. Aftimos concluded.
Reference
- 1、Lin N, et al. Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ advanced/metastatic breast cancer (mBC) with or without brain metastases (BM): DESTINYBreast-12 primary results. ESMO Congress 2024, LBA18
- 2、Pistilli B, et al. Efficacy, safety and biomarker analysis of ICARUS-BREAST01: A phase 2 study of patritumab deruxtecan (HER3-DXd) in patients (pts) with HR+/HER2- advanced breast cancer (ABC). ESMO Congress 2024, Abstract 340O
