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797 Genomic and transcriptomic profiles associated with response to eribulin and nivolumab combination in HER-2 negative metastatic breast cancer
  1. Changhee Park1,
  2. Koung Jin Suh2,
  3. Se Hyun Kim2,
  4. Seock-Ah Im1,
  5. Min Hwan Kim3,
  6. Jae Ho Jeong4,
  7. Kyoung Eun Lee5,
  8. Yeon Hee Park6,
  9. Hee-Jun Kim7,
  10. Eun Kyung Cho8,
  11. In Sil Choi9,
  12. Seung-Jae Noh10,
  13. Inkyung Shin10,
  14. Dae-Yeon Cho10 and
  15. Jeehyun Kim2
  1. 1Seoul National University Bundang Hospital, Seoul, Republic of Korea
  2. 2Seoul National University Bundang Hospital, Seongnam, Gyeonggi-Do, Republic of Korea
  3. 3Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
  4. 4Asan Medical Center, Seoul, Republic of Korea
  5. 5Ewha Womans University Hospital, Seoul, Republic of Korea
  6. 6Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
  7. 7Chung-Ang University College of Medicine, Seoul, Republic of Korea
  8. 8Gil Medical Center, Incheon, Republic of Korea
  9. 9Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea
  10. 10PentaMedix Co., Ltd., Seongnam, Gyeonggi-do, Republic of Korea
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Combination of eribulin and immune checkpoint inhibitor (ICI) showed durable response for HER-2 negative metastatic breast cancer (MBC) patients, but PD-L1 expression was not associated with efficacy. Here, we report the whole exome sequencing (WES) and whole transcriptome sequencing (WTS) analysis of pretreatment tumor tissues from the phase II clinical trial of the eribulin and nivolumab combination in patients with HER-2 negative MBC to find potential biomarker (KORNELIA trial, Identifier: NCT04061863).

Methods We acquired whole exome sequencing (WES) data from 76 patients, and whole transcriptomic sequencing (WTS) data from 58 patients. Patients achieved progression free survival (PFS) ≥ 6 months were defined as PFS6-responders and otherwise as PFS6-nonresponders. We explored the potential biomarkers from WES and WTS, and analyzed how they are associated with efficacy.

Results PFS6 rate in this study cohort was 34.5%. PFS6-responders tended to have higher TMB compared with PFS6-nonresponders (median TMB 6.6 vs. 5.1 mut/Mb, p = 0.309). TMB-high patients (≥ 8 mut/Mb) showed showed tendency to higher PFS compared with TMB-low patients (median PFS 8.0 months, 95% confidence interval [CI] 5.6 ~ 14.6 for TMB-high and 4.3 months, 95% CI 3.0 ~ 5.6 for TMB-low, p = 0.07). Comprehensive analysis related to homologous recombination deficiency (HRD), which include mutational signature 3, somatic HRD-related gene mutation, and HRD scores, showed that overall HRD was associated with poor response to the combination regimen. Specifically, when patients were divided into two groups by median HRD score, patients with high HRD score showed significantly lower PFS6 rate (23.7% vs. 50.0%, p = 0.031) and significantly shorter PFS compared to patients with low HRD score (median PFS 4.2 months [95% CI 2.6 ~ 5.6] vs. 6.5 [95% CI 5.3 ~ 14.3], p = 0.025). WTS data showed antigen presentation (AP) gene set enrichment scores were high in PFS6-responders and the patients with high scores showed significantly longer PFS compared with the other patients. In addition, the proportion of naïve B-cell and plasma cell were significantly higher in the long responders (≥ 18 months).

Conclusions In conclusion, we found that high TMB and B-cell related enrichment were associated with good efficacy while HRD was associated with poor efficacy of eribulin plus nivolumab in patients with HER-2 negative metastatic breast cancer. The implications from our study would need to be considered when designing the clinical trial in terms of biomarker enrichment and inclusion/exclusion criteria.

Trial Registration NCT04061863

Ethics Approval Institutional review boards of Seoul National University Bundang Hospital

Number B-1811–505-004

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