Abstract PD18-07: Omission of chemotherapy in the treatment of HER2-positive and hormone-receptor positive metastatic breast cancer – interim results from the randomized phase 3 DETECT V trial
Authors: Janni Wolfgang , Fehm Tanja , Müller Volkmar , Schochter Fabienne , De Gregorio Amelie , Decker Thomas , Hartkopf Andreas , Just Marianne , Sagasser Jacqueline , Schmidt Marcus , Wimberger Pauline , Banys-Paluchowski Maggie , Fasching Peter A. , Rack Brigitte , Riethdorf Sabine , Schneeweiss Andreas , Wallwiener Diethelm , Meier-Stiegen Franziska , Krawczyk Natalia , Hoffmann Oliver , Blohmer Jens-Uwe , Niederacher Dieter , Neubauer Hans , Pantel Klaus , Friedl Thomas W. , Huober Jens 
Published: March 2023

Abstract
Background: Metastatic breast cancer (MBC) is an incurable disease and both the improvement of survival and maintenance of quality of life (QoL) are equally important aims of treatment planning. In patients with HER2-positive MBC, taxane-based chemotherapy in combination with dual HER2 targeted therapy with trastuzumab (T) and pertuzumab (P) is the standard of care first line therapy. However, adverse events are well-known side effects of any cytostatic treatment and can seriously impact the patients’ QoL. In addition, in HER2-positive MBC activated estrogen receptor (ER) signaling is associated with primary or secondary resistance. Thus, for patients with HER2-positive and hormone-receptor (HR) positive MBC, the synergistic combination of dual HER2-targeted therapy plus endocrine therapy might offer a better treatment option compared to cytotoxic chemotherapy-based treatments. Methods: Between 9/2015 and 11/2022, the multicenter phase III DETECT V trial randomized patients with HER2-positive and HR-positive (i.e. ER positive and/or progesterone-receptor positive) MBC in the 1st-3rd line setting 1:1 to receive T and P combined with either endocrine therapy or chemotherapy followed by maintenance therapy with T, P and endocrine therapy. Chemotherapy and the endocrine agents could be chosen from a variety of available regimens according to physicians’ choice. Based on emerging data strongly suggesting an additional benefit of CDK4/6 inhibitors, an amendment came into effect in January 2019 with the addition of ribociclib to both treatment arms after 124 patients had been randomized. The primary objective of DETECT V is to compare tolerability between the chemotherapy-free and chemotherapy-containing treatment arm; secondary objectives comprise the comparison of PFS, OS and safety. Here we report results of an unplanned interim analysis with data cut off June 22th 2022. Results: The results reported here are based on 153 patients for whom end of study was documented at the time of data cut off for this interim analysis (120 patients randomized before and 33 patients randomized after the addition of ribociclib; 115 patients in the 1st line setting; 77 and 76 patients in the chemotherapy-free and chemotherapy-containing arm, respectively). Overall survival (OS) and progression-free survival (PFS) did not differ between patients receiving chemotherapy-free and chemotherapy-containing treatment (median OS not yet reached vs. 37.2 months, hazard ratio 0.87, 95% CI 0.51 – 1.50, p = 0.63; median PFS 15.6 vs. 14.9 months, hazard ratio 0.98, 95% CI 0.64 – 1.52, p = 0.93). Study treatment was terminated prematurely significantly less often in the chemotherapy-free treatment arm (43.9% vs. 72.2%, p = 0.001). Furthermore, tolerability was better for the chemotherapy-free treatment as there were less adverse events (AEs) of any grade (585 vs. 793; 70 vs. 71 patients affected), less AEs grade 3 or higher (66 vs. 90; 33 vs. 48 patients affected) and less serious adverse events (45 vs. 52; 28 vs. 29 patients affected) reported in the chemotherapy-free treatment arm as compared to the chemotherapy-containing treatment arm. Conclusion: These preliminary results suggest that chemotherapy-free treatment for patients with triple-positive MBC might be an effective and well tolerated option.
Citation Format: Wolfgang Janni, Tanja Fehm, Volkmar Müller, Fabienne Schochter, Amelie De Gregorio, Thomas Decker, Andreas Hartkopf, Marianne Just, Jacqueline Sagasser, Marcus Schmidt, Pauline Wimberger, Maggie Banys-Paluchowski, Peter A. Fasching, Brigitte Rack, Sabine Riethdorf, Andreas Schneeweiss, Diethelm Wallwiener, Franziska Meier-Stiegen, Natalia Krawczyk, Oliver Hoffmann, Jens-Uwe Blohmer, Dieter Niederacher, Hans Neubauer, Klaus Pantel, Thomas W. Friedl, Jens Huober. Omission of chemotherapy in the treatment of HER2-positive and hormone-receptor positive metastatic breast cancer – interim results from the randomized phase 3 DETECT V trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD18-07.