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Proffered papers 3 - Best abstracts

127O - Tumour mutational burden and immune infiltration as independent predictors of response to neoadjuvant immune checkpoint inhibition in early TNBC in GeparNuevo

Date

24 May 2020

Session

Proffered papers 3 - Best abstracts

Presenters

Thomas Karn

Citation

Annals of Oncology (2020) 31 (suppl_2): S58-S61. 10.1016/annonc/annonc121

Authors

T. Karn1, C. Denkert2, K.E. Weber3, U. Holtrich4, C. Hanusch5, B.V. Sinn6, B. Higgs7, P. Jank8, J. Huober9, J. Blohmer10, W.D. Schmitt11, S. Wu7, M. van Mackelenbergh12, C. Schem13, E. Stickeler14, C. Jackisch15, M. Untch16, A. Schneeweiss17, S. Loibl18

Author affiliations

  • 1 University Hospital, Goethe University, 60590 - Frankfurt am Main/DE
  • 2 Institute Of Pathology, Uniklinikum Giessen und Marburg, 35043 - Marburg/DE
  • 3 Statistics, German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg/DE
  • 4 University Hospital, Goethe University, 60590 - Frankfurt/DE
  • 5 Gynäkologie, Rotkreuzklinikum München, 80634 - München/DE
  • 6 Institute Of Pathology, Charité - Universitätsmedizin Berlin, 10117 - Berlin/DE
  • 7 Tm, Medimmune + LAP&P, 20878 - Gaithersburg/US
  • 8 Pathology Department, Uniklinikum Giessen und Marburg (UKGM), 35043 - Marburg/DE
  • 9 Dept Of Gynecology, Breast Center, Universitaetsfrauenklinik Ulm, 89075 - Ulm/DE
  • 10 Gynäkologie, Charité - Universitätsmedizin Berlin, 10713 - Berlin/DE
  • 11 Pathology, Charité - Universitätsmedizin Berlin, 10117 - Berlin/DE
  • 12 Gynäkologie, University Hospital Kiel, 24105 - Kiel/DE
  • 13 Gynäkologie, Mammazentrum Hamburg, 20357 - Hamburg/DE
  • 14 Department Of Gynecology And Obstetrics, Universitaetsklinikum Aachen (UKA), 52074 - Aachen, Germany/DE
  • 15 Frauenklinik, Klinikum Offenbach GmbH, 63069 - Offenbach am Main/DE
  • 16 Clinic For Gynecology, Gynecologic Oncology And Obstetrics, Helios Klinikum Berlin Buch, 13125 - Berlin/DE
  • 17 Gynecological Oncology, National Center for Tumor Disease, 69115 - Heidelberg/DE
  • 18 Department Of Medicine And Research, German Breast Group (GBG) Forschungs GmbH, 63263 - Neu-Isenburg/DE
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Resources

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Abstract 127O

Background

The predictive value of tumor mutatio1nal burden (TMB), alone or in combination with an immune gene expression profile (GEP), for response to neoadjuvant therapy in early triple negative breast cancer (TNBC) is currently not known, neither for immune checkpoint blockade (ICB) nor conventional chemotherapy.

Methods

We obtained both whole exome sequencing and RNA-Seq data from pre-treatment samples of 149 TNBC of the recent neoadjuvant ICB trial GeparNuevo. In a predefined analysis we assessed the predictive value of TMB and a previously developed immune GEP for pathological complete remission (pCR).

Results

Median TMB was 1.52 mut/Mb (range 0.02-7.65) and was significantly higher in patients with pCR (median 1.87 vs. 1.39; P=0.005). In multivariate analysis odds ratios for pCR per mut/Mb were 2.06 (95% CI 1.33-3.20, P=0.001) among all patients, 1.77 (95% CI 1.00-3.13, P=0.049) in the durvalumab treatment arm, and 2.82 (95% CI 1.21-6.54, P=0.016) in the placebo treatment arm, respectively. We also found that both continuous TMB and immune GEP (or tumor infiltrating lymphocytes) independently predicted pCR. When we stratified patients in groups based on the upper tertile of TMB and median GEP, we observed a pCR rate of 82% (95% CI 60%-95%) in the group with both high TMB and GEP, in contrast to only 28% (95% CI 16%-43%) in the group with both low TMB and GEP.

Conclusions

TMB and immune gene expression profile add independent value for pCR prediction. Our results recommend further analysis of TMB in combination with immune parameters to individually tailor therapies in breast cancer.

Clinical trial identification

NCT02685059.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

H.W. & J. Hector-Stiftung.

Disclosure

C. Denkert: Honoraria (self): Teva; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): Amgen; Honoraria (self): MSD; Honoraria (self): Celgene; Honoraria (self): AstraZeneca; Shareholder/Stockholder/Stock options: Sividon Diagnostics. K.E. Weber: Shareholder/Stockholder/Stock options, Licensing/Royalties: Sividon Diagnostics. C. Hanusch: Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Lilly; Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer. B. Higgs: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. J. Huober: Honoraria (self), Research grant/Funding (self): Celgene; Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self), Research grant/Funding (self): Hexal; Honoraria (self): Lilly; Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): Eisai; Honoraria (self): AbbVie; Honoraria (self): Daiichi. J-U. Blohmer: Honoraria (self): AstraZeneca; Honoraria (self): Genomic Health; Honoraria (self): MSD Oncology; Honoraria (self): Myriad Genetics; Honoraria (self): Novartis/Pfizer; Honoraria (self): Roche; Honoraria (self): Sonoscape. W.D. Schmitt: Honoraria (self): AstraZeneca. S. Wu: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. M. van Mackelenbergh: Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): Genomic Health; Non-remunerated activity/ies: Novartis; Non-remunerated activity/ies: Lilly. C. Jackisch: Honoraria (self): Roche; Honoraria (self): Celgene. M. Untch: Honoraria (institution), Non-remunerated activity/ies: AbbVie; Honoraria (institution), Non-remunerated activity/ies: Amgen; Honoraria (institution), Non-remunerated activity/ies: AstraZeneca; Honoraria (institution): BMS; Honoraria (institution), Non-remunerated activity/ies: Celgene GmbH; Honoraria (institution), Non-remunerated activity/ies: Daiji Sankyo; Honoraria (institution), Non-remunerated activity/ies: Eisai GmbH; Honoraria (institution): Lilly Deutschland; Honoraria (institution), Non-remunerated activity/ies: Lilly Int.; Honoraria (institution), Non-remunerated activity/ies: MSD Merck; Honoraria (institution), Non-remunerated activity/ies: Mundipharma; Honoraria (institution), Non-remunerated activity/ies: Myriad Genetics; Honoraria (self), Non-remunerated activity/ies: Odonate; Honoraria (institution), Non-remunerated activity/ies: Pfizer GmbH; Honoraria (self): Puma; Honoraria (institution), Non-remunerated activity/ies: Roche Pharma AG; Honoraria (institution): Sanofi Aventis; Honoraria (institution), Non-remunerated activity/ies: Teva; Honoraria (institution), Non-remunerated activity/ies: Novartis; Honoraria (institution): Pierre Fabre. A. Schneeweiss: Honoraria (self), Research grant/Funding (self): Roche; Honoraria (self): Celgene; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Tesaro; Honoraria (self): Lilly. S. Loibl: Honoraria (institution), Research grant/Funding (institution), Non-remunerated activity/ies: AstraZeneca; Honoraria (institution), Research grant/Funding (institution), Non-remunerated activity/ies: Celgene; Honoraria (institution), Research grant/Funding (institution): AbbVie; Honoraria (institution), Research grant/Funding (institution): Amgen; Honoraria (institution), Research grant/Funding (institution): Novartis; Honoraria (institution), Research grant/Funding (institution): Pfizer; Honoraria (institution), Research grant/Funding (institution): Roche; Honoraria (institution): Seattle Genetics; Honoraria (institution): PriME/Medscape; Honoraria (self): Chugai; Research grant/Funding (institution): Teva; Research grant/Funding (institution): Vifor; Honoraria (institution), Research grant/Funding (institution): Daiichi-Sankyo; Honoraria (institution): Lilly; Honoraria (institution): Samsung; Honoraria (institution): Eirgenix. All other authors have declared no conflicts of interest.

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