An analysis of the chemotherapy cohort from the ADAPT trial found that nanoparticle albumin-bound (nab)-paclitaxel (PAC) had similar outcomes to solvent-based (sb)-PAC in patients with high-risk hormone receptor (HR)-positive, HER2-negative early breast cancer who were preselected by recurrence score and endocrine response. The findings presented at the 2024 San Antonio Breast Cancer Symposium (SABCS) (Abstract GS3-04) raise questions about optimal regimen selection.
“Both taxane-based regimens had manageable safety profiles and low discontinuation rates and can be considered as standard chemotherapy options in high-risk, HR-positive, HER2-negative early breast cancer disease patients,” said Sherko Kuemmel, MD, PhD, lead author of the study and a breast surgeon at the German Medical Institute in Berlin.
Launched in 2012 and conducted by the West German Study Group, the ADAPT trial was designed to evaluate the use of biomarkers to assess risk and predict treatment outcomes in early breast cancer. It established that the trifecta of clinical risk, genomic risk, and endocrine response allows for optimal selection of patients for endocrine therapy or chemotherapy in HR-positive, HER2-negative disease.
The results presented at this year’s SABCS included five-year outcomes and toxicity data from patients who received chemotherapy regimens. For this cohort, 1,129 patients were randomly assigned to receive sb-PAC, and 1,104 were assigned nab-PAC. To be included, patients were required to have stage 0-I disease, a recurrence score of 12–25, and a Ki-67 index of 10% or higher after endocrine therapy, or must have had a similar stage with a recurrence score higher than 25. In addition, patients who had stage II–III or grade 3 cancer, a baseline Ki-67 index of more than 40%, and tumor size greater than 1 cm could be included without recurrence score or endocrine therapy response testing.
Primary endpoints were five-year disease-free survival (DFS) and invasive disease-free survival (iDFS) rates. With nab-PAC, the DFS was 84.9% and iDFS was 85.7%. With sb-PAC, those rates were 81.7% and 82.9%, respectively. Secondary endpoints included relapse-free survival, which was 86.9% with nab-PAC and 84% for sb-PAC, and overall survival, where the respective rates were 94% and 92.9%.
Dr. Kuemmel said that no new safety signals were observed, with 7.8% of patients discontinuing nab-PAC because of an adverse event (AE) compared with 7.9% for sb-PAC. There were also two nontreatment-related deaths in both study groups. More grade 3 or higher AEs occurred in patients receiving nab-PAC, but there was also less neuropathy.
During the SABCS session, Hope S. Rugo, MD, director of breast oncology and clinical trials education at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center, suggested that the toxicity findings may be an argument in favor of switching to nab-PAC if a patient shows early evidence of neuropathy. “Neuropathy, other than secondary cancers, is one of the biggest long-term toxicities from early-stage curable therapy,” she said.
Dr. Kuemmel noted that the phase 3 ADAPTCycle trial is underway and is evaluating ribociclib (Kisqali) in combination with endocrine therapy versus standard-of-care chemotherapy followed by adjuvant endocrine therapy. The trial has randomly assigned 1,684 patients and is scheduled to be completed in 2027.
Dr. Kuemmel reported relationships with Roche, Exact Science, Lilly, Pfizer, Novartis, MSD, Hologic, Seagen, AstraZeneca, Daiichi Sankyo, Gilead, and Agendia.
Dr. Rugo reported relationships with various companies, including AstraZeneca, Pfizer, and Novartis.
