Ribociclib Improves Outcomes in HR-Positive, HER2-Positive Metastatic Breast Cancer
Key Clinical Takeaways
- Design/Population: The phase 3 DETECT V trial enrolled 262 treated patients with HR-positive, HER2-positive metastatic breast cancer to receive trastuzumab and pertuzumab with either endocrine therapy (chemotherapy-free arm) or chemotherapy, followed by HER2-targeted maintenance plus endocrine therapy. A 2019 protocol amendment added ribociclib to both arms, enabling assessment of CDK4/6 inhibition within HER2-directed treatment strategies.
- Key Outcomes: Across the full study population, chemotherapy-free therapy demonstrated similar OS and PFS compared with chemotherapy-containing regimens. However, the addition of ribociclib significantly improved outcomes:
- OS and PFS were substantially prolonged overall, regardless of treatment arm.
- In chemotherapy-containing regimens, ribociclib produced notable improvement in both survival endpoints.
- In chemotherapy-free regimens, ribociclib significantly improved PFS, with a strong trend toward improved OS.
- Exploratory analyses further showed that chemotherapy-free treatment plus ribociclib outperformed chemotherapy-containing therapy without ribociclib.
- Clinical Relevance: These findings indicate that chemotherapy-free, endocrine-based regimens augmented with ribociclib may represent a highly effective alternative to chemotherapy in HR-positive, HER2-positive metastatic breast cancer. Incorporating CDK4/6 inhibition into dual HER2 blockade may allow for less toxic, more targeted treatment approaches while preserving or improving survival outcomes.
Wolfgang Janni, MD, PhD, University of Ulm, Germany, discusses final efficacy results from the phase 3 DETECT V trial, which assessed trastuzumab, pertuzumab, and ribociclib paired with either chemotherapy-free or chemotherapy-based treatment strategies in patients with hormone receptor–positive, HER2-positive metastatic breast cancer.
Ribociclib consistently prolonged overall and progression-free survival across analyses, with benefit observed in both treatment approaches, supporting the feasibility and potential efficacy of chemotherapy-free regimens enhanced by CDK4/6 inhibition in this population.
These results were presented at the 2025 San Antonio Breast Cancer Symposium in San Antonio, Texas.
Transcript:
Hello, my name is Wolfgang Janni, I'm working at the University of Ulm in Southern Germany, and I'm delighted to present the final analysis of the DETECT V trial at Thursday's rapid fire session at the San Antonio Breast Cancer Symposium 2025.
The DETECT V trial was based on the hypothesis that in triple-positive breast cancer, that is HER2-positive and hormone receptor–positive metastatic breast cancer, dual-targeted treatment in combination with endocrine therapy might be effective without chemotherapy.
We designed a phase 3 randomized trial, randomizing 270 patients between standard-of-care chemotherapy in combination with dual-targeted HER2 treatment consisting of trastuzumab and pertuzumab, followed by dual-blockade maintenance therapy in combination with endocrine therapy versus the experimental arm with dual HER2-targeted treatment in combination with endocrine treatment without chemotherapy. After 124 patients, about half of the study, we added ribociclib to both arms based on data from several studies that CDK4/6 inhibition might enhance the efficacy of endocrine therapy, especially in triple-positive breast cancer patients.
The main result of the study is that induction chemotherapy before the dual-targeted treatment combination with endocrine therapy, plus or minus ribociclib, did not significantly improve progression-free survival or overall survival in these triple-positive metastatic breast cancer patients– this was true in univariate as well as in multivariate analysis. Since we sequentially added ribociclib, we were also very interested in the efficacy of the addition of ribociclib in our patients, especially since last year the results of the PATINA study were presented here at the San Antonio Breast Cancer Symposium.
We basically compared the first 124 patients without ribociclib in both arms versus the second cohort, where ribociclib was added in both arms. This is not a randomized comparison but a sequential cohort comparison; however, the main patient characteristics were well balanced between the first cohort and the second cohort with and without ribociclib. cohorts. Again, looking at progression-free survival and overall survival, we saw a significant improvement in progression-free survival, a significant improvement in overall survival with the addition of ribociclib.
In summary, we believe that in triple-positive breast cancer it is a reasonable option to omit chemotherapy, especially in patients in which we are concerned about the side effects of chemotherapy, such as elderly patients. However, at the same time, the addition of a CDK4/6 inhibitor, in our study ribociclib, can enhance the efficacy of the maintenance therapy in combination with dual HER2-targeted treatment by combining endocrine single-agent therapy with a CDK4/6 inhibitor, which is in line with the results we saw from PATINA.
Source:
Janni W, Fehm T, Muller V, et al. Efficacy analysis of the randomized phase III DETECT V trial: Treatment de-escalation by omission of chemotherapy and the effect of adding ribociclib in HER2-positive and hormone-receptor positive metastatic breast cancer. Presented at SABCS 2025. December 9 - 12, 2025. San Antonio, Texas. Abstract RF4-02
