From: cancertherapyadvisor.com
It may be possible to safely omit chemotherapy for patients with HER2-positive, hormone receptor (HR)-positive metastatic breast cancer, according to an updated analysis of the DETECT V study. Wolfgang Janni, MD, PhD, of the University Hospital Ulm in Ulm, Germany presented the findings at the San Antonio Breast Cancer Symposium 2025.
The randomized, multicenter, phase 3 DETECT V study (NCT02344472) enrolled patients with HER2-positive, HR-positive metastatic breast cancer for treatment in the first- to third-line setting. Patients were randomly assigned to trastuzumab plus pertuzumab with either endocrine therapy or chemotherapy, followed by maintenance including trastuzumab, pertuzumab, and endocrine therapy. After a protocol amendment, investigators added ribociclib to endocrine therapy for both arms.
The primary endpoint was the modified adverse event (AE) score, including all AEs of grade 3 or higher. Neutropenia was excluded unless grade 4 or higher. Alopecia, rash, peripheral neuropathy, and hand-food syndrome were included if grade 2 or higher. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). The effects of adding ribociclib were evaluated in exploratory, nonrandomized analyses. Dr Janni presented findings with the final efficacy analysis, with a database lock of June 24, 2025.
The study included 262 patients in a modified intention-to-treat population, with 132 patients in the chemotherapy-free treatment arm and 130 patients in the chemotherapy-containing treatment arm. Patients had a median age of 60 years in both randomized arms. more than three-quarters of patients in both arms received the first line treatment in the metastatic setting. Additionally, 142 patients received ribociclib while 120 patients did not.
The primary study objective was met. Modified AE scores indicating the proportion of patients affected were 52.3% (95% CI, 43.8%-60.8%) in the chemotherapy-free treatment arm compared with 76.9% (95% CI, 69.7%-84.2%) in the chemotherapy-containing treatment arm (P <.001). Diarrhea was the most common AE in both arms.
The study was not powered for PFS or OS comparisons between treatment arms. However, investigators did not detect a significant difference in OS or PFS between the treatment arms. Median PFS durations were 19.5 months for the chemotherapy-free treatment arm and 23.0 months for the chemotherapy-containing treatment arm (hazard ratio [HR], 1.15; 95% CI, 0.82-1.62; P =.419). Median OS times were not reached for the chemotherapy-free treatment arm and 46.1 months for the chemotherapy-containing treatment arm (HR, 0.98; 95% CI, 0.60-1.59; P =.928).
Modified AE scores were 69.0% (95% CI, 61.4%-76.6%) with ribociclib and 59.2% (95% CI, 50.4%-68.0%) without (P =.097). Median PFS (29.7 vs 15.6 months; HR, 0.48; 95% CI, 0.34-0.67) and median OS (not reached vs 46.1 months; HR, 0.43; 95% CI, 0.26-0.72) both favored the ribociclib arm.
“In conclusion, chemotherapy-free treatment with dual HER2-targeted therapy plus endocrine therapy might be an effective treatment option for selected patients with triple-positive metastatic breast cancer, in which chemotherapy should be avoided,” Dr Janni said in his presentation. He also noted that adding ribociclib may support improved survival.
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