Pooled Analysis of HER2-Targeting Antibody-Drug Conjugate in Metastatic Breast Cancer
Posted: Friday, July 16, 2021
The HER2-targeting antibody-drug conjugate RC48-ADC demonstrated consistent efficacy with no new safety signals in patients with HER2-positive and HER2-low advanced or metastatic breast cancer, according to Jiayu Wang, MD, of the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, and colleagues. The pooled analysis of the phase I C001 CANCER and phase Ib C003 CANCER trials, which was presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 1022), also suggested 2.0 mg/kg of RC48-ADC may have a more favorable benefit-risk ratio than other dose levels.
Using data from these trials, the investigators identified 118 female patients with HER2-positive (59.3%) or HER2-low (40.7%) breast cancer who were treated with RC48-ADC. The objective response rates with 1.5, 2.0, and 2.5 mg/kg were 22.2%, 42.9%, and 40.0%, respectively, in the HER2-positive subgroup. The median duration of progression-free survival was 4.0 months with 1.5 mg/kg, 5.7 months with 2.0 mg/kg, and 6.3 months with 2.5 mg/kg. The objective response rate and median duration of progression-free survival were 39.6% and 5.7 months, respectively, in the HER2-low subgroup. In the immunohistochemistry (IHC) 2-positive/ fluorescence in situ hybridization (FISH)-negative patients, the objective response rate was 42.9%; the median duration of progression-free survival was 6.6 months. Although the COVID-19 pandemic led to the postponement of treatment for some IHC1-positive patients, the objective response rate and median duration of progression-free survival reached 30.8% and 5.5 months, respectively.
Increased levels of aspartate aminotransferase (64.4%) and alanine aminotransferase (59.3%), hypoesthesia (58.5%), and decreased white blood cell (48.3%) and neutrophil (47.5%) counts were among the most frequently reported treatment-related adverse events; the majority were grade 1 or 2. The most common treatment-related adverse events of grade 3 or higher were decreased neutrophil counts (16.9%), increased levels of gamma-glutamyl transferase (12.7%), and fatigue (11.9%).
Disclosure: Dr. Wang reported no conflicts of interest. For full disclosures of the other study authors, visit coi.asco.org.