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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.

Background: Data on the oncologic safety of omission of axillary lymph node dissection (ALND) in node positive (N+) patients who downstage to ypN0 with neoadjuvant chemotherapy (NAC) is sparse. Additionally, there is no consensus on which axillary staging procedure should be used in this setting, sentinel lymph node biopsy (SLNB) alone or in combination with localization and retrieval of the clipped positive node, also known as targeted axillary dissection (TAD). Whether the reduction in the false negative rate observed with TAD translates into a significant reduction in the rate of axillary recurrence is unknown. We sought to evaluate oncologic outcomes after omission of ALND in a large, real-world cohort of breast cancer (BC) patients and to compare rates of axillary recurrence after SLNB with dual tracer mapping vs. TAD. Methods: Data were collected from 19 centers in the Oncoplastic Breast Consortium (OPBC) and EUBREAST networks. Patients with T1-4 biopsy-proven N1-3 BC who underwent NAC followed by axillary staging with either SLNB with dual tracer mapping or TAD and who were pathologically node negative (ypN0) were included. ypN0 was defined as the absence of any tumor or isolated tumor cells. Competing risk analysis was performed to assess the cumulative incidence rates of axillary recurrence, locoregional recurrence, and any invasive (locoregional or distant) recurrence. Two-year cumulative incidence rates were compared between TAD and SLNB using the Gray’s test. Type I error rate was set to 0.05 (α). Results: We included 785 patients (565 treated with SLNB and 220 with TAD) treated with NAC followed by surgery from 01/2014-12/2020. Median patient age was 50 years. The majority (57%) of patients had clinical T2 tumors, and 95% had N1 disease. Most (55%) were HER2+, and 21% were triple negative. Most patients (81%) received anthracycline and taxane-based chemotherapy regimens, but NAC regimens differed between patients treated with TAD and those treated with SLNB (Table 1). All patients with HER2+ tumors received anti HER2 therapy. Nodal radiotherapy was administered to 76% of patients, and was more common in patients who underwent TAD (82% TAD vs 74% SLNB, p=0.017). Breast pathologic complete response (ypT0/is) was more frequent among those patients that had TAD (80% TAD vs. 66% SLNB, p< 0.001). TAD localization was with wire in 46%, radioactive seed in 40%, ultrasound in 5%, tattoo in 2%, and with a combination of these techniques in 7%. The clipped node was successfully retrieved in 94% of TAD cases. The median number of lymph nodes removed was lower in the TAD group compared to the SLNB group [3 (IQR 3-5) vs 4 IQR 3-5), p< 0.001], as was the median number of sentinel lymph nodes [3 (IQR 2-4) vs 4 IQR 3-5), p< 0.001] (Table 1). The 5-year rates of any axillary recurrence, locoregional recurrence, and any invasive recurrence in the entire cohort were 1.1% (95%CI 0.39-2.4%), 3.1% (95%CI 1.6-5.3%) and 10% (95%CI 7.6-13%), respectively. The two-year cumulative incidence of axillary recurrence did not differ between patients treated with TAD compared to SLNB (0% vs 0.9%, p=0.19). Conclusion: Early axillary recurrence after omission of ALND in patients who successfully downstage from N+ to ypN0 with NAC is a rare event following both SLNB or TAD, and was not significantly lower in TAD than SLNB. Although longer follow-up is needed to confirm these findings, the main advantage of TAD seems to be a reduction in the number of lymph nodes removed. Overall, these results support omission of ALND in patients who successfully downstage to node negative disease after NAC. Table 1: Clinicopathological Features of the Study Cohort, Stratified by Axillary Staging Technique Citation Format: Giacomo Montagna, Mary Mrdutt, Astrid Botty, Andrea V. Barrio, Varadan Sevilimedu, Judy C. Boughey, Tanya L. Hoskin, Laura H. Rosenberger, E Shelley Hwang, Abigail Ingham, Bärbel Papassotiropoulos, Bich Doan Nguyen-Sträuli, Christian Kurzeder, Danilo Diaz Aybar, Denise Vorburger, Dieter Michael Matlac, Edvin Ostapenko, Fabian Riedel, Florian Fitzal, Francesco Meani, Franziska Fick, Jacqueline Sagasser, Jörg Heil, Konstantin J. Dedes, Laszlo Romics, Maggie Banys-Paluchowski, Maria Del Rosario Cueva Perez, Marcelo Chavez Diaz, Martin Heidinger, Mathias K. Fehr, Mattea Reinisch, Nadia Maggi, Nicola Rocco, Nina Ditsch, Oreste Davide Gentilini, Regis Resende Paulinelli, Sebastian Sole Zarhi, Sherko Küemmel, Simona Bruzas, Simona Di Lascio, Tamara Parissenti, Uwe Güth, Valentina Ovalle, Christoph Tausch, Monica Morrow, Thorsten Kühn, Walter P. Weber. Oncological Outcomes Following Omission of Axillary Lymph Node Dissection in Node Positive Patients Downstaging To Node Negative with Neoadjuvant Chemotherapy: the OPBC-04/EUBREAST-06/OMA study [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 GS4-02.