Abstract 256P
Background
We have conducted a phase II trial (NEWBEAT) to evaluate efficacy of triple therapy with nivolumab, paclitaxel and bevacizumab in patients (pts) with HER2-negative MBC. Immunological status and response to immune checkpoint inhibitor would be different between recurrent and de novo stage IV breast cancer (BC), however the data is limited. In an ancillary study (WJOG9917BTR), immunological analyses were performed to elucidate this question.
Methods
The NEWBEAT study enrolled 57 pts and showed that median PFS and OS was 14.0 months and 32.5 months, respectively. In this biomarker study, Immune status of circulating and tumor microenvironment (TME) of the pts was assessed by multicolor IHC in TME using biopsy samples before treatment, and by multicolor flowcytometer or multiplex ELISA in peripheral blood before and after treatment.
Results
Biomarker study included 50 pts (36 with recurrent BC and 14 with de novo stage IV BC). The ORR was not different in pts with recurrent or de novo stage IV BC (67% and 64%, respectively). Although the PFS was not significantly different in recurrent or de novo stage IV pts (14.3 and 18.8 months, respectively, p = 0.230), significantly higher rate of the responders (defined as PFS ≥1y) was observed in de novo stage IV pts compared to recurrent pts (79% and 47%, respectively, p = 0.0393). Tumor infiltrating T cells in TNBC, especially in recurrent pts, were higher than that in HR-positive BC, consisted with previous studies. On the other hand, in circulating immune cells, the PD-L1 and/or VEGFR2 positive CD4/CD8 T cells were significantly higher in pts with recurrent than de novo stage IV, but no difference in the amount of total CD4/CD8 T cells. Moreover, the amount of soluble CD163 before treatment were higher in pts with recurrent than de novo stage IV. These results suggested that immune status of not only TME but also circulating immune cells in pts with recurrent diseases were more exhausted than in de novo stage IV.
Conclusions
Our analysis showed the different immune status between recurrent and de novo stage IV BC. This data suggests that recurrent BC require different immunotherapeutic strategy compared to de novo stage IV BC.
Clinical trial identification
UMIN000029590.
Editorial acknowledgement
Legal entity responsible for the study
West Japan Oncology Group.
Funding
Ono Pharmaceutical.
Disclosure
Y. Ozaki: Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo, Chugai Pharma. S. Kitano: Financial Interests, Personal and Institutional, Sponsor/Funding: Ono pharmaceutical, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Eisai, Astellas, Gilead Sciences, Takara Bio, PACT Pharm, Regeneron, MSD; Financial Interests, Personal and Institutional, Research Grant: AMED, JSPS; Financial Interests, Personal and Institutional, Advisory Board: Immunity Research, AstraZeneca, Pfizer, Novartis, Sumitomo Dainippon, Bristol-Myers Squibb, Regeneron, GSK, Rakuten Medical, PMDA; Financial Interests, Personal and Institutional, Invited Speaker: Sanofi, Taiho, Ayumi Pharmaceutical. J. Tsurutani: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, AstraZeneca, Eisai Inc.; Financial Interests, Personal, Expert Testimony: Daiichi Sankyo, Taiho Inc.; Financial Interests, Personal, Invited Speaker: West Japan Oncology Group; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Funding: Daiichi Sankyo, West Japan Oncology Group; Financial Interests, Institutional, Invited Speaker: FSJD. T. Iwasa: Financial Interests, Institutional, Funding: Ono pharmaceutical. M. Takahashi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, Pfizer, Eisai. T. Mukohara: Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo, Eisai, MSD, Pfizer, Novartis, Sanofi, Chugai, AstraZeneca, Ono; Financial Interests, Personal and Institutional, Research Grant: Sysmex; Financial Interests, Personal, Other, lecture fee: Eli Lilly, Kyowa Kirin, Taiho. N. Masuda: Financial Interests, Personal, Invited Speaker: Chugai, AstraZeneca, Eisai, Eli-Lilly, Pfizer; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Eli-Lilly, Kyowa-Kirin, MSD, Novartis, Pfizer, Sanofi; Non-Financial Interests, Invited Speaker: Japan Breast Cancer Research Group, Japanese Breast Cancer Society. M. Futamura: Financial Interests, Personal and Institutional, Funding: Ono pharmaceutical ; Financial Interests, Personal, Other, Personal fees: Chugai, Taiho, Takeda, Novartis, Eisai. H. Minami: Financial Interests, Personal, Invited Speaker: Bayer, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Dainihon Sumitomo, Eizai, Kyowa-Kirin, Ono Pharmaceutical, Ohtsuka, Pfizer, Takeda, Abbvie, Taiho, Lilly, Novartis, Nihon Servier; Financial Interests, Institutional, Research Grant: Dainihon Sumitomo, Eizai, Kyowa-Kirin, Nihon Shinyaku, Ono Pharmaceutical, Sanofi, Takeda, Nihon Kayaku, Shionogi, Taiho, Lilly, Mitsubishi Tanabe Pharma, Chugai Pharma, MSD, Boehringer Ingelheim, Daiichi Sankyo, Teijin Pharma, Bayer, Ohtsuka. K. Matsumoto: Financial Interests, Institutional, Invited Speaker, Local PI of the clinical trial: Ono, Chugai. Y. Tanabe Hashimoto: Financial Interests, Institutional, Research Grant: Ono pharmaceutical. H. Kawabata: Financial Interests, Institutional, Research Grant: Ono pharmaceutical ; Financial Interests, Personal and Institutional, Research Grant: MSD, Daiichi Sankyo, Novartis, Taiho, Chugai. K. Yoshimura: Financial Interests, Personal, Research Grant: Ono pharmaceutical ; Financial Interests, Personal, Invited Speaker: AstraZeneca, Eisai, Otsuka, Nippon Kayaku, Eli Lilly, Novartis, Boehringer Ingelheim, Chugai. T. Takano: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Chugai, Eli Lilly. All other authors have declared no conflicts of interest.