Abstract P5-02-42: Soluble CD163 may be a predictive biomarker of the efficacy of nivolumab plus chemotherapy in patients with HER2-negative metastatic breast cancer (WJOG9917BTR)

Abstract Background: We have conducted a phase II trial (WJOG9917B) to evaluate efficacy of triple therapy with nivolumab, paclitaxel and bevacizumab in patients (pts) with HER2-negative metastatic breast cancer (MBC). Although soluble CD163 has been reported as a potential biomarker for predicting the efficacy of nivolumab in melanoma, however the data is limited in breast cancer. In an ancillary study (WJOG9917BTR), serum level of soluble CD163 were evaluated to elucidate this question. Methods: The main study enrolled 57 pts and showed that median Progression-free survival (PFS) and overall survival (OS) was 14.0 months and 32.5 months, respectively, with a median follow-up of 29.5 months. We have collected blood samples from consenting patients. Serum samples were collected at pretreatment, cycle 1 day 8 and other time points, which were used to measure the concentrations of cytokines, chemokines, and other surrogate proteins. PFS, OS, and response were analyzed in association with the biomarker data using the Kaplan–Meier method, log-rank tests as appropriate. Results: Biomarker study included 50 pts (36 with recurrent BC and 14 with de novo stage IV BC). The median amount of soluble CD163 before treatment was 562.3 (pg/ml) (range: 158.7-1518.0), and the baseline CD163 levels were higher in pts with recurrent than de novo stage IV (p = 0.0099). Other clinical factors including tumor subtypes, liver metastasis, response, PFS or OS were not significantly associated with the baseline CD163 levels. The kinetic changes in serum soluble CD163 after treatment were divided into two groups; one group (30 patients, CD163 increased group) had increased soluble CD163 immediately after administration (Cycle 1 Day 8), with a median PFS of 18.2; the other group (20 patients, CD163 decreased group) had decreased CD163 immediately after administration, with a median PFS of 13.6. There was a significantly difference in PFS between these two groups (hazard ratio 0.50 [0.26-0.93], log-rank test, p = 0.0263), but not in OS (p = 0.0548). These results suggested that the early change of serum soluble CD163 may be a predictive biomarker of efficacy of nivolumab plus chemotherapy in pts with HER2-negative MBC. Conclusions: Soluble CD163 may be a predictive biomarker for early detection of the efficacy of nivolumab plus chemotherapy in pts with HER2-negative MBC. (UMIN000029590) Citation Format: Toru Mukohara, Yukinori Ozaki, Shigehisa Kitano, Makiko Yamashita, Daiki Ikarashi, Junji Tsurutani, Tsutomu Iwasa, Masato Takahashi, Norikazu Masuda, Manabu Futamura, Hironobu Minami, Koji Matsumoto, Yuko Tanabe, Hidetaka Kawabata, Kenichi Yoshimura, Toshimi Takano. Soluble CD163 may be a predictive biomarker of the efficacy of nivolumab plus chemotherapy in patients with HER2-negative metastatic breast cancer (WJOG9917BTR). [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 P5-02-42.