Abstract PD7-01: Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: A multicenter retrospective study (ROSET-BM study)
Authors: Yamanaka Takashi , Niikura Naoki , Nomura Hironori , Kusama Hiroki , Yamamoto Mitsugu , Matsuura Kazuo , Inoue Kenichi , Takahara Sachiko , Kita Shosuke , Yamaguchi Miki , Aruga Tomoyuki , Shibata Nobuhiro , Shimomura Akihiko , Ozaki Yuri , Shiraishi Kazuhiro , Sakai Shuji , Kiga Yoko , Izutani Tadahiro , Shiosakai Kazuhito , Tsurutani Junji 
Published: March 2023

Background: Brain metastases (BM) occur in 20%-50% of patients (pts) with HER2-positive (HER2+) metastatic breast cancer (MBC), and their presence is a poor prognostic factor. Leptomeningeal carcinomatosis (LMC) occurs in 12%–43% of pts with MBC. Therapeutic options for BC pts with BM and/or LMC are limited. Results of the DESTINY-Breast01 and DESTINY-Breast03 studies have shown the clinical benefit of trastuzumab deruxtecan (T-DXd) in HER2+ MBC pts with stable BM; however, the study populations were small and did not include pts with active BM (untreated or progressive) and/or LMC. This data gap is addressed in the present study. Methods: ROSET-BM (UMIN000044995) is a multicenter, retrospective chart review study of pts who received T-DXd for HER2+ MBC with BM and LMC between May 25, 2020, and April 30, 2021, in a standard-of-care setting. Overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. Additionally, in the pts with brain imaging data, intracranial (IC)-ORR and IC-PFS were evaluated by independent radiologists to provide central review according to RECIST v1.1. Active BM were determined by independent central review (ICR). Pts whose baseline and pre-baseline brain imaging data were compared and confirmed increased tumor size, or pts with new lesions were classified as active BM. LMC was determined by ICR using brain imaging. Results: In the study period, 62 sites participated, enrolling 113 pts with HER2+ MBC and BM were treated with T-DXd. After exclusion of data from 9 who did not meet the criteria for inclusion, 104 pts were included in the analysis. In the 104 pts, 70.2% (n=73) were active BM, 16.3% (n=17) were active BM with LMC, 5.8% (n=6) were stable BM, 1.9% (n=2) were only LMC, and 5.8% (n=6) were not classified. Symptomatic BM were observed in 30.8% (n=32). Median number of prior lines of therapy was 4 (range, 1–15). Median duration of follow up from first T-DXd treatment was 11.2 months. ORR assessed by investigator was 55.7% (complete response [CR], 5.2%) in all pts, 51.7% (CR, 6.9%) in symptomatic BM pts (n=29), and 57.4% (CR, 4.4%) in asymptomatic BM pts (n=68). Among all pts, median PFS was 16.1 months (95%CI, 12.0–n/a), and median OS was not reached (OS at 1 year was 74.9%). In the 19 pts with LMC, 1-year PFS and OS were 60.7% (95%CI, 34.5–79.1) and 87.1% (95%CI, 57.3–96.6), respectively (neither reached the median). Of the 89 pts with brain lesion imaging data (at both baseline and follow-up), IC-ORR was 62.7% (CR, 0.0%). IC-PD was observed in 5.9% (n=3) of pts. Median IC-PFS was 16.1 months (95%CI, 12.2–n/a). In all pts, the most common event and adverse event leading to discontinuation of T-DXd were PD (27 pts, 26.0%) and interstitial lung disease (19 pts,18.3%), respectively. Conclusion: The results of this retrospective chart review show that T-DXd has promising efficacy in HER2+ MBC pts with active BM and LMC. This study was funded by Daiichi Sankyo Co., Ltd.

Citation Format: Takashi Yamanaka, Naoki Niikura, Hironori Nomura, Hiroki Kusama, Mitsugu Yamamoto, Kazuo Matsuura, Kenichi Inoue, Sachiko Takahara, Shosuke Kita, Miki Yamaguchi, Tomoyuki Aruga, Nobuhiro Shibata, Akihiko Shimomura, Yuri Ozaki, Kazuhiro Shiraishi, Shuji Sakai, Yoko Kiga, Tadahiro Izutani, Kazuhito Shiosakai, Junji Tsurutani. Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: A multicenter retrospective study (ROSET-BM 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 PD7-01.