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ePoster Display

147P - Genomic profile and response prediction of eribulin mesylate-based neoadjuvant chemotherapy in triple-negative breast cancer patients

Date

16 Sep 2021

Session

ePoster Display

Presenters

Tomomi Nishimura

Citation

Annals of Oncology (2021) 32 (suppl_5): S407-S446. 10.1016/annonc/annonc687

Authors

T. Nishimura1, N. Masuda2, K. Kawaguchi3, M. Takada3, Y. Maeshima1, S. Tanaka3, R. Velaga3, Y. Kikawa4, T. Kadoya5, H. Bando6, R. Nakamura7, Y. Yamamoto8, T. Ueno9, H. Yasojima2, H. Ishiguro10, S. Morita11, S. Ohno12, H. Haga13, S. Ogawa14, M. Toi1

Author affiliations

  • 1 Department Of Breast Surgery, Kyoto University Graduate School of Medicine, 606-8501 - Kyoto/JP
  • 2 Department Of Surgery, Breast Oncology, NHO Osaka National Hospital, 540-0006 - Osaka/JP
  • 3 Department Of Breast Surgery, Kyoto University Hospital, 606-8507 - Kyoto/JP
  • 4 Department Of Breast Surgery, Kobe City Medical Center General Hospital, 650-0047 - Hyogo/JP
  • 5 Department Of Breast Surgery, Hiroshima University Hospital, Hiroshima University, 734-0037 - Hiroshima/JP
  • 6 Faculty Of Medicine, University Of Tsukuba, Breast and Endocrine Surgery, 305-8575 - Ibaraki/JP
  • 7 Department Of Breast Surgery, Chiba Cancer Center, 260-0801 - Chiba/JP
  • 8 Department Of Breast And Endocrine Surgery, Kumamoto University, Graduate School of Medical Sciences, 860-8556 - Kumamoto/JP
  • 9 Breast Surgical Oncology Department, The Cancer Institute Hospital of JFCR, 135-8550 - Koto-ku/JP
  • 10 Breast Oncology Service, Saitama Medical University International Medical Center, 350-1298 - Saitama/JP
  • 11 Department Of Biomedical Statistics And Bioinformatics, Kyoto University Graduate School of Medicine, 606-8507 - Kyoto/JP
  • 12 Breast Oncology Center, The Cancer Institute Hospital of JFCR, 135-8550 - Tokyo/JP
  • 13 Department Of Diagnostic Pathology, Kyoto University Hospital, 606-8507 - Kyoto/JP
  • 14 Department Of Pathology And Tumor Biology, Kyoto University Graduate School of Medicine, 606-8501 - Kyoto/JP
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Abstract 147P

Background

Little is known about predictive factors for eribulin mesylate (eribulin)-based chemotherapy. In this translational research of a randomised neoadjuvant phase II study, we aimed to explore predictive factors for eribulin-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) using tumour genomic profiling.

Methods

Tumour tissues were collected from the Japan Breast Cancer Research Group-22 trial, examined either 4 cycles of paclitaxel plus carboplatin (arm A1) or eribulin plus carboplatin (arm A2), followed by anthracycline-based therapy in patients with aged <65y and homologous recombination deficiency (HRD) score ≥42, and any age carrying pathogenic germline variant (PGV) of BRCA1/2, and also examined non-carboplatin regimens, either started with eribulin plus cyclophosphamide (arm B1) or eribulin plus capecitabine (arm B2) in patients with aged <65y with HRD score <42 or aged ≥65y without PGV of BRCA1/2. Tumour BRCA1/2 mutation (tBRCA1/2m) and HRD were analysed in 86 cases. Fifty tumour samples were also analysed by target sequencing capturing 189 breast cancer driver genes.

Results

Although tumours without tBRCA1/2m contain high HRD score tumours, tumours with tBRCA1/2 m had higher HRD score, especially with tBRCA1m, than those without. HRD-high tumours (A1+ A2) showed higher pathological complete response (pCR) rates as compared with HRD-low tumours (B1+B2) [56% (25 (=15+10) /45 (=23+22)), 21% (6 (=1+5)/ 29 (=14+15)), respectively, p=0.003]. In the A1+A2, pCR rates were similar between tumours with tBRCA1/2m (57%) and those without (55%). However, when stratified by tBRCA1m and tBRCA2m, pCR rates of tBRCA2m tumours were remarkably higher than those of tBRCA1m [89% (8/9) vs 36% (5/14)]. Among tBRCA1m tumours, A1 group achieved a 63% (5/8) pCR rate, but A2 group showed no pCR (0/6). The tumour genomic profile revealed that tumours with HRD<42 had mutations in PIK3CA and PTEN frequently (61%, 22%, respectively). Contrary, these abnormalities are rare in tumours with HRD>=42 (5%, 0%).

Conclusions

tBRCA1m and tBRCA2m may have a different role in predicting pCR of these chemotherapies. HRD is a good predictor in assessing sensitivity of eribulin based therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Japan Breast Cancer Research Group.

Funding

Eisai Co., Ltd.

Disclosure

N. Masuda: Financial Interests, Personal, Speaker’s Bureau: Chugai; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Eli-Lilly; Financial Interests, Institutional, Funding: Eisai; Financial Interests, Institutional, Funding: Takeda; Financial Interests, Institutional, Funding: Chugai; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Eli-Lilly; Financial Interests, Institutional, Funding: Kyowa-Kirin; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Eisai; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Nihon-Kayaku; Financial Interests, Institutional, Funding: Daiichi Sankyo; Non-Financial Interests, Personal, Member of the Board of Directors: Board of directors, Japanese Breast Cancer Society (JBCS); Non-Financial Interests, Personal, Member of the Board of Directors: Board of directors, Japan Breast Cancer Research Group Association (JBCRG). K. Kawaguchi: Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: KBCRN; Financial Interests, Personal, Invited Speaker: Chugai Pharmacetual. M. Takada: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Nippon Kayaku; Financial Interests, Personal, Invited Speaker: Kyowa Kirin; Financial Interests, Institutional, Research Grant: Yakult. Y. Kikawa: Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Chugai. H. Bando: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Chugai. R. Nakamura: Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Nipponkayaku; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: AstraZeneca. Y. Yamamoto: Non-Financial Interests, Personal, Member of the Board of Directors: Japanese Breast Cancer Society; Non-Financial Interests, Personal, Member of the Board of Directors: Japan Breast Cancer Research Group; Financial Interests, Personal, Invited Speaker, Advisory Board: Chugai; Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Personal, Invited Speaker, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Kyowa Kirin; Financial Interests, Institutional, Research Grant: Kyowa Kirin; Financial Interests, Personal, Invited Speaker, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Nippon Kayaku; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Esai. T. Ueno: Financial Interests, Personal, Royalties: Chugai; Financial Interests, Personal, Royalties: Eisai; Financial Interests, Personal, Royalties: AstraZeneca; Financial Interests, Personal, Royalties: Novartis; Financial Interests, Personal, Royalties: Taiho. S. Morita: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb Company; Financial Interests, Personal, Speaker’s Bureau: Chugai; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly Japan; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Pfizer Japan; Financial Interests, Personal, Speaker’s Bureau: Taiho. S. Ohno: Financial Interests, Personal, Speaker’s Bureau: Chugai; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Institutional, Sponsor/Funding: Taiho; Financial Interests, Institutional, Sponsor/Funding: Eisai. S. Ogawa: Financial Interests, Personal, Advisory Board: KAN Research Institute, Inc.; Financial Interests, Institutional, Funding: KAN Research Institute, Inc.; Financial Interests, Personal, Advisory Board: ChordiaTherapeutics, Inc.; Financial Interests, Institutional, Funding, Others(accepted a researcher ): ChordiaTherapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Asahi Genomics Co., Ltd.; Financial Interests, Institutional, Funding: Sumitomo Dainippon Pharma Co., Ltd.; Financial Interests, Institutional, Funding: Otsuka Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Funding: Eisai Co., Ltd. M. Toi: Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Personal, Invited Speaker: Kyowa-Kirin; Financial Interests, Personal, Advisory Board: Kyowa-Kirin; Financial Interests, Institutional, Research Grant: Kyowa-Kirin; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Institutional, Research Grant: Taiho; Non-Financial Interests, Personal, Member of the Board of Directors: JBCRG association; Financial Interests, Institutional, Research Grant: JBCRG association; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Invited Speaker: Exact Science; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Konica Minolta; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: Shimadzu; Financial Interests, Institutional, Research Grant: Shimadzu; Non-Financial Interests, Personal, Member of the Board of Directors: KBCRN; Non-Financial Interests, Personal, Member of the Board of Directors: OOTR; Financial Interests, Personal, Invited Speaker: Yakult; Financial Interests, Institutional, Research Grant: Yakult; Financial Interests, Personal, Invited Speaker: Nippon Kayaku; Financial Interests, Institutional, Research Grant: Nippon Kayaku; Financial Interests, Institutional, Research Grant: AFI technologies; Financial Interests, Personal, Advisory Board: Athenex Oncology; Financial Interests, Personal, Advisory Board: Bertis; Financial Interests, Personal, Advisory Board: Terumo; Financial Interests, Personal, Advisory Board: Luxonus; Financial Interests, Institutional, Research Grant: Luxonus; Financial Interests, Institutional, Research Grant: Shionogi; Financial Interests, Institutional, Research Grant: GL Science; Financial Interests, Personal, Advisory Board: Kansai Medical Net. All other authors have declared no conflicts of interest.

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