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Poster display session

1010 - Gene alteration in triple negative breast cancer patients in a phase I/II study of combination therapy with eribulin and olaparib.

Date

11 Sep 2017

Session

Poster display session

Presenters

Akihiko Shimomura

Citation

Annals of Oncology (2017) 28 (suppl_5): v74-v108. 10.1093/annonc/mdx365

Authors

A. Shimomura1, K. Yonemori1, N. Masuda2, K. Aogi3, M. Takahashi4, Y. Naito5, S. Shimizu6, R. Nakamura7, A. Hamada8, H. Michimae9, J. Hashimoto10, H. Yamamoto11, C. Shimizu1, K. Tamura1, Y. Fujiwara1

Author affiliations

  • 1 Department Of Breast And Medical Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 2 Department Of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, 540-0006 - Osaka/JP
  • 3 Department Of Breast Surgery, National Hospital Organization Shikoku Cancer Center, 791-0280 - Matsuyama/JP
  • 4 Department Of Breast Surgery, National Hospital Organization Hokkaido Cancer Center, 003-0804 - Sapporo/JP
  • 5 Department Of Breast And Medical Oncology, National Cancer Center Hospital East, 277-8577 - Tokyo/JP
  • 6 Department Of Breast And Endocrine Surgery, Kanagawa Cancer Center, 241-8515 - Yokohama/JP
  • 7 Department Of Breast Surgery, Chiba Cancer Center Hospital, 260-8717 - Chiba/JP
  • 8 Division Of Molecular Pharmacology, Nationl Cancer Center, 104-0045 - Tokyo/JP
  • 9 Department Of Clinical Medicine, Kitasato University, 108-8641 - Tokyo/JP
  • 10 Department Of Medical Oncology, St. Luke's International Hospital, 104-8560 - Tokyo/JP
  • 11 Department Of Medical Oncology, National Hospital Organization Kumamoto Medical Center, 860-0008 - Kumamoto/JP
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Resources

Abstract 1010

Background

Olaparib (Lynparza®) shows efficacy in patients with triple negative breast cancer (TNBC). Eribulin is one of the standard therapies for metastatic breast cancer. A phase I/II study of combination therapy with eribulin and olaparib capsule (EO study) was conducted on patients with TNBC. We investigated the correlation between response to combination therapy and homologous recombination deficiency (HRD).

Methods

Tissue samples were collected from patients who participated in the EO study. Archival tissue samples were examined for gene alterations using the Foundation Medicine, Inc. (FMI) gene panel. Pathogenic or likely pathogenic gene alterations were extracted from all detected gene alterations using the FMI data dictionary. This dictionary uses the COSMIC database, relevant literature, and internal evidence to determine the reportable status of an alteration. HRD-related genes were defined as previously described (Konstantinopoulos PA, et al. Cancer Discovery, 2015). Correlation between presence of HRD and response to combination therapy was tested using chi-square test.

Results

A total of 32 tissue samples were collected. Nineteen samples were collected from the phase I and 13 samples from the phase II. Seventeen patients were treated at the recommended dose. Thirty-three gene mutations were detected. The most frequent gene mutations were TP53 (n = 27, 84.4%), PIK3CA (n = 7, 21.9%), BRCA1 (n = 5, 15.6%), MLL3 (n = 5, 15.6%), and AKT1 (n = 4, 12.5%). We detected 32 gene amplifications, with MYC being the most common (n = 6, 18.8%). Eight homozygous deletions were detected, and the most frequent was loss of PTEN (n = 4, 12.5%). We detected 10 gene rearrangements. HRD, including BRCA1/2 mutations, was observed in nine patients. The overall response rate (RR) and clinical benefit rate (CBR) were 31.3% and 78.1%, respectively. The RRs in patients with HRD and without HRD were 44.4% and 26.1%, respectively (p=.4072). The CBRs for the HRD and non-HRD groups were 66.7% and 82.6%, respectively (p =.3702).

Conclusions

Eighty-three gene alterations were detected in TNBC pts receiving combination olaparib/eribulin therapy. Patients with HRD had numerically higher response rate.

Clinical trial identification

UMIN000018721

Legal entity responsible for the study

Japan

Funding

Japan Agency for Medical Research and Development, AstraZeneca

Disclosure

A. Shimomura: Research fund from AstraZeneca, Inc. K. Yonemori: Lecture fee from Eisai. N. Masuda: Research Funds from Chugai, Eisai. Honorarium from Chugai, AstraZeneca. K. Aogi: Honoraria from Chugai, Eisai, Sanofi, SRL, AstraZeneca, Taiho, Novartis, Daiichi Sankyo, Mochida Pharmaceutical, Ono Pharmaceutical, Otsuka Pharmaceutical, Nihon Medi-Physics and Eli Lilly. M. Takahashi: Lecture fee from Eisai, AstraZeneca, Chugai. Y. Naito: Honoraria from Eisai, Chugai, Taiho, Novartis, Eli Lilly, Meiji Seika, Bayer Yakuhin, Roche Diagnostics. Research funds from Merck Serono, AstraZeneca, Eli Lilly, Nippon Kayaku. C. Shimizu: Research funds from Chugai, Pfizer, Eli lilly, MSD. K. Tamura: Research funds from AstraZeneca, Daiichi Sankyo, Pfizer, MSD. Y. Fujiwara: Lecture fee from AstraZeneca, Eisai, Daiichi Sankyo, Taiho, Chugai, Eli Lilly, Yakut. Research funds from Taiho, Takeda, Chugai, Eli Lilly, Nippon Kayaku. All other authors have declared no conflicts of interest.

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