Abstract RF4-02: 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

Abstract Background: Current data support that metastatic hormone receptor-positive (HR+) and HER2-positive (HER2+) breast cancer offers distinct treatment options targeting both the hormone receptor and the HER2-pathway. This might lead to increased treatment efficacy with the potential of omitting chemotherapy in these patients. The aim of the randomized multicenter phase III DETECT V trial was to analyze the efficacy of chemotherapy free and CDK4/6 inhibitor containing treatment strategies compared to current standard treatment. Methods: Between 09/2015 and 11/2022, 271 patients with HER2+ and HR+ MBC in the 1st-3rd line setting were randomized 1:1 to receive trastuzumab and pertuzumab combined with either endocrine therapy or chemotherapy followed by maintenance therapy with dual HER2 targeted and endocrine therapy. Chemotherapy and the endocrine agents could be chosen from a variety of available regimens according to physicians’ choice. In January 2019, the protocol was amended with the addition of the CDK4/6 inhibitor ribociclib to both treatment arms. The primary objective of DETECT V was to compare tolerability between the treatment arms, and secondary objectives comprised the comparison of overall survival (OS), progression-free survival (PFS) and safety, as well as the evaluation of the effect of adding ribociclib to both treatment arms. Here we report results of the final efficacy analyses as based on the modified ITT set of 262 patients (9 patients did not receive any study treatment and were excluded). Of these, 120 patients were recruited before the addition of ribociclib (59 and 61 patients in the chemotherapy-free and chemotherapy-containing treatment arm, respectively), and 142 patients were recruited after the addition of ribociclib (73 and 69 patients in the chemotherapy-free and chemotherapy-containing treatment arm, respectively). Results: Median patient age was 60 years, 202 (77.1%) of patients were in the first line setting and 137 (52.3%) patients had a metastasis-free interval (from primary diagnosis) exceeding 12 months. The overall comparison between all patients receiving chemotherapy-free and chemotherapy-containing treatment showed no significant difference with regard to OS and PFS (median OS not reached vs 46.1 months, HR 0.98, 95% CI 0.60 - 1.59, p = 0.93; median PFS 19.5 vs 23.0 months, HR 1.15, 95% CI 0.82 - 1.62, p = 0.42). However, both OS and PFS were significantly improved by the (non-randomized) addition of ribociclib (OS: median OS not reached vs 46.1 months, HR 0.43, 95% CI 0.26 - 0.72, p = 0.001; PFS: median PFS 29.7 vs 15.6 months, HR 0.48, 95% CI 0.34 - 0.67, p < 0.001). A separate analysis for the two treatment arms showed that the addition of ribociclib to chemotherapy-containing treatment significantly improved both OS (median OS not reached vs 38.7 months, HR 0.30, 95% CI 0.14 - 0.64, p = 0.002) and PFS (median PFS 33.1 vs 15.4 months, HR 0.35, 95% CI 0.21 - 0.59, p < 0.001), while the addition of ribociclib to chemotherapy-free treatment significantly improved PFS (median PFS 27.2 vs 15.6 months, HR 0.61, 95% CI 0.38 - 0.98, p = 0.040) but not OS (median OS not reached in both groups, HR 0.60, 95% CI 0.30 - 1.23, p = 0.163). An exploratory cross-cohort comparison revealed significantly improved outcome for patients receiving chemotherapy-free treatment plus ribociclib vs chemotherapy-containing treatment without ribociclib (OS: median OS not reached vs 38.7 months, HR 0.48, 95% CI 0.24 - 0.94, p = 0.033; PFS: median PFS 27.2 vs 15.4 months, HR 0.53, 95% CI 0.33 - 0.85, p = 0.008). Conclusion: Our results suggest that chemotherapy-free treatment for patients with HER2+ and HR+ MBC may be a valuable and effective treatment alternative, and may improve survival with the addition of ribociclib. Citation Format: W. Janni, T. Fehm, V. Müller, J. Blohmer, A. De Gregorio, T. Decker, A. Hartkopf, N. Ditsch, M. Schmidt, P. Wimberger, T. Engler, M. Banys-Paluchowski, P. A. Fasching, B. Rack, A. Schneeweiss, K. Pantel, T. W. Friedl, F. Schochter, J. Huober. 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 [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF4-02.