Abstract P2-16-05: Efficacy of response- and toxicity-guided neoadjuvant chemotherapy in elderly early breast cancer patients: Results of WSG ADAPT elderly sub-trial
Authors: Kuemmel Sherko , Gluz Oleg , Christgen Matthias , Potenberg Jochem , Hackmann John , von Schumann Raquel , Graeser Monika , Mangold Marina , Wuerstlein Rachel , Kates Ronald , Kreipe Hans H. , Nitz Ulrike , Harbeck Nadia ,   West German Study Group
Published: March 2020

Abstract
Introduction: More than 1/3 of early breast cancers (EBC) are diagnosed in women ≥ 70 years. Although polychemotherapy has been shown to be more effective than monochemotherapy also in these patients, only limited prospective data on efficacy of neoadjuvant therapy are available so far. Here, we present results of the prospective ADAPT Elderly sub-study from the WSG ADAPT umbrella protocol.
Methods: Patients ≥70 years with high-risk HR+/HER2- EBC (i.e. Recurrence Score (RS)&gt;25 or RS 12-25 with post-endocrine Ki67 of &gt;10% or ≥cN2) or HR-/HER2- EBC were treated by 2 cycles of liposomal doxorubicin (Myocet® 60 mg/m2)/cyclophosphamide 600 mg/m2 (MC). In case of clinical response by ultrasound (&gt;50% reduction in the sum of two largest diameters) and no AE grade 3-4, patients received an additional 2 cycles MC, otherwise they were switched to 6 cycles of paclitaxel (80 mg/m2) weekly. A sample size of n=150 was planned to demonstrate non-inferiority of the response- and toxicity-guided regimen vs. 4 cycles MC in responding patients (25% assumed pCR). The study was stopped early due to slow recruitment.
Results: Between 09/2014 and 10/2015, 83 EBC patients from 31 centers were registered; 78 started with therapy (40 HR+/HER2-; 38 HR-/HER2-). Median age was 74 years. 64% had G3 tumors, 66% cT24, and 34% cN+. Median Ki67 was 40%. 75/78 pts underwent stratification after 2 cycles; 1 pt withdrew consent: 45(61%) were responders with no severe toxicities, 29 (39%) non-responders or suffered toxicity grade 3-4. Surgical information is available in 72 patients (43 responder/no toxicity, 29 no response/toxicity groups respectively). pCR was observed in 7 patients in the responder/no toxicity group (i.e. 16% irrespective of HR status) and in n=3 patients in the no response/toxicity group (10%). Updated efficacy and safety data will be presented at the meeting.
Discussion: In one of the largest neoadjuvant chemotherapy-studies specifically for elderly pts with HER2- EBC, we observed a lower than expected pCR rate after 4 cycles of anthracycline-containing neoadjuvant chemotherapy. Taxane-based standard chemotherapy may thus be preferable in this population. Nevertheless, neoadjuvant chemotherapy seems feasible in elderly pts with high-risk HER2- EBC and should further be explored in the context of potential pCR-based (de)escalation strategies.
Citation Format: Sherko Kuemmel, Oleg Gluz, Matthias Christgen, Jochem Potenberg, John Hackmann, Raquel von Schumann, Monika Graeser, Marina Mangold, Rachel Wuerstlein, Ronald Kates, Hans H. Kreipe, Ulrike Nitz, Nadia Harbeck, West German Study Group. Efficacy of response- and toxicity-guided neoadjuvant chemotherapy in elderly early breast cancer patients: Results of WSG ADAPT elderly sub-trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-05.