J. Huober (Ulm, Germany)

University Hospital Ulm

Author Of 2 Presentations

 On-Demand ePoster Display

66P - Baseline menopausal status, Ki-67 and stromal tumor-infiltrating lymphocytes (TILs) and association with outcome in triple-negative breast cancer (TNBC): exploratory analysis in GeparSixto

Abstract

Background

Several trials confirmed a survival benefit from temporary menopause during or after chemotherapy (CT) for patients with estrogen receptor-negative early BC. We investigated the impact of menopause on TNBC outcome after neoadjuvant CT (NACT).

Methods

GeparSixto evaluated the addition of carboplatin to anthracycline-taxane-based NACT. We aimed to determine the impact of menopausal status on continuous Ki-67 and TILs from baseline biopsies in all patients, and according to germline (g)BRCA1 status. TILs and gBRCA status were centrally assessed. Secondary objectives were the impact of age (≤40 vs >40 years) on baseline Ki-67 and TILs in all patients and according to gBRCA1 status, baseline menopausal status and age on pathological complete response (pCR, ypT0 ypN0), disease-free survival (DFS) and distant disease-free survival (DDFS) according to pCR.

Results

43/315 included patients had a gBRCA1 mutation (14.8%); mean Ki-67 was higher in ≤40 compared to >40 years (63.9 vs 57.9%, p=0.045) and in pre- compared to postmenopausal patients (63.1 vs 53.9%, t-test p=0.001). Mean TILs did not differ according to age (38.4 vs 33.5%, p=0.126) or menopausal status (35.9 vs 33.0%, p=0.311). There was no difference in Ki-67 or TILs according to age and menopausal status in gBRCA1 carriers. pCR rate was higher in women ≤40 years (55.4 vs 44.4%) and premenopausal (50.5 vs 36.6%). For multivariate analysis for DFS refer to the below table. Neither young age nor premenopausal status at baseline predicted for DFS. In non-pCR patients, premenopausal status at baseline but not age ≤40 years was associated with a higher relapse risk (Table). Similar results were obtained for DDFS.

pCR (ypT0 ypN0) OR (95% CI)* p-value 5-year DFS rate (N=315) HR (95% CI)* p-value 5-year DFS rate in non-pCR (N=173) HR (95% CI)* p-value 5-year DFS rate in pCR (N=142) HR (95% CI)* p-value
Age
>40 years (N=232) 41.4% 1 74.9% 1 62.7% 1 91.7% 1
≤40 years (N=83) 55.4% 1.47 (0.85-2.55) 0.167 81.2% 0.87 (0.48-1.55) 0.631 68.8% 0.83 (0.43-1.61) 0.583 91.6% 1.11 (0.26-4.68) 0.890
Menopausal status
Postmenopausal (N=123) 36.6% 1 78.4% 1 70.2% 1 92.3% 1
Premenopausal (N=192) 50.5% 1.54 (0.92-2.57) 0.101 75.3% 1.49 (0.88-2.52) 0.137 58.8% 1.79 (1.01-3.18) 0.046 91.4% 1.16 (0.26-5.20) 0.849

* adjusted for tumor stage, nodal status, tumor grade, Ki67, TILs and carboplatin use.

Conclusions

In patients with early TNBC, premenopausal compared to postmenopausal status is associated with a higher cancer cell proliferation at baseline and a higher risk of relapse in case of no pCR.

Legal entity responsible for the study

GBG.

Funding

Has not received any funding.

Disclosure

S.I. Labidi-Galy: Honoraria (self): AstraZeneca; Honoraria (institution): Novimmune. A. Schneeweiss: Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses, Research Grant, Travel expenses, Medical writing grant: Celgene; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses, Expert testimony, Research Grant, Travel expenses: Roche; Honoraria (institution), Research Grant: AbbVie; Honoraria (self), Expert testimony, Honoraria: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses, Honoraria, Travel expenses: Pfizer; Honoraria (self), Honoraria: Novartis; Honoraria (self), Honoraria: MSD; Honoraria (self), Honoraria: Tesaro; Honoraria (self), Honoraria: Lilly. J-U. Blohmer: Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): Lilly; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self), Honoraria (institution): Sysmex; Honoraria (self): Roche; Honoraria (self): Pierre Fabre. J. Huober: Honoraria (self): Lilly; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): AbbVie; Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): Celgene; Honoraria (self): Roche; Travel/Accommodation/Expenses: Daiichi; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer; Honoraria (institution): Novartis; Honoraria (institution): Hexal. T. Link: Honoraria (self): Teva; Honoraria (self): Tesaro; Honoraria (self): MSD; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Amgen; Honoraria (self): Clovis; Honoraria (self): Celgene; Honoraria (self): Lilly; Honoraria (self): Myriad. C. Hanusch: Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Lilly. C. Jackisch: Honoraria (self): Celgene. P.A. Fasching: Honoraria (self): Novartis; Honoraria (institution): Biontech; Honoraria (self): Pfizer; Honoraria (self): Daiichi Sankyo; Honoraria (self): AstraZeneca; Honoraria (self): Eisai; Honoraria (self): Merck Sharp & Dohme; Honoraria (institution): Cepheid; Honoraria (self): Lilly; Honoraria (self): Pierre Fabre; Honoraria (self): Seattle Genetics; Honoraria (self): Roche; Honoraria (self): Hexal. K.E. Rhiem: Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): MSD. C. Denkert: Honoraria (institution), Oncobiome project: European Commission H2020; Honoraria (institution), INTEGRATE-TN project: German Cancer Aid Translational Oncology; Honoraria (self): Novartis; Honoraria (self): Roche; Honoraria (self): MSD Oncology; Honoraria (self): Daiichi Sankyo; Honoraria (self): AstraZeneca; Honoraria (self): Molecular Health; Honoraria (institution): Myriad; Honoraria (self): Merck; Shareholder/Stockholder/Stock options, Cofounder/shareholder until 2016: Sividon diagnostics; Licensing/Royalties: VMScope digital pathology software; Licensing/Royalties: WO2020109570A1 - cancer immunotherapy; Licensing/Royalties: WO2015114146A1 and WO2010076322A1- therapy response. M. Untch: Honoraria (institution), All fees to the institution/employer: AbbVie; Honoraria (institution), All fees to the institution/employer: Amgen GmbH; Honoraria (institution), All fees to the institution/employer: AstraZeneca; Honoraria (institution), All fees to the institution/employer: BMS; Honoraria (institution), All fees to the institution/employer: Celgene GmbH; Honoraria (institution), All fees to the institution/employer: Daiichi Sankyo; Honoraria (institution), All fees to the institution/employer: Eisai GmbH; Honoraria (institution), All fees to the institution/employer: Lilly Deutschland; Honoraria (institution), All fees to the institution/employer: Lilly Int.; Honoraria (institution), All fees to the institution/employer: MSD Merck; Honoraria (institution), All fees to the institution/employer: Mundipharma; Honoraria (institution), All fees to the institution/employer: Myriad Genetics; Honoraria (institution): Odonate; Honoraria (institution), All fees to the institution/employer: Pfizer GmbH; Honoraria (institution): PUMA Biotechnology; Honoraria (institution), All fees to the institution/employer: Roche Pharma AG; Honoraria (institution), All fees to the institution/employer: Sanofi Aventis Deutschland GmbH; Honoraria (institution), All fees to the institution/employer: TEVA Pharmaceuticals Ind Ltd.; Honoraria (institution), All fees to the institution/employer: Novartis; Honoraria (institution), All fees to the institution/employer: Pierre Fabre, Clovis Oncology, Seatlle Genetics. S. Loibl: Honoraria (institution), honorario for lectures and ad boards paid to institute: AbbVie; Honoraria (institution), honorario for lectures and ad boards paid to institute: Celgene; Honoraria (institution), honorarium for lectures paid to institute: PriME/Medscape; Honoraria (self), lecture: Chugai; Honoraria (self), Honoraria (institution), honorario paid to institute: Daiichi Sankyo; Honoraria (institution), honorarium for ad boards paid to institute: Lilly; Honoraria (institution), advisor honorarium paid to institute: BMS; Honoraria (institution), advisor honorarium paid to institute: Puma; Honoraria (institution), paid to institute: Immunomedics; Honoraria (institution), honorarium for lectures and ad boards paid to institute: AstraZeneca; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Pierre Fabre; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Merck; Honoraria (institution), advisor honorarium paid to institute: EirGenix; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Amgen; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Novartis; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Pfizer; Honoraria (institution), grant and honorarium paid to institute: Roche; Honoraria (institution), paid to institute: Seagen; Licensing/Royalties, Immunsignature in TNBC: EP14153692.0. All other authors have declared no conflicts of interest.

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104P - Clinical characteristics of patients (pts) with complete response (CR) to abemaciclib-based endocrine therapy (ET) in MONARCH 2 (M2) and MONARCH 3 (M3)

Abstract

Background

Abemaciclib is an oral cyclin-dependent kinase 4 & 6 inhibitor, dosed on a continuous schedule, approved for the treatment of hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) combined with ET. In this pt population, CR is rarely seen with ET alone. Pt/disease characteristics may correlate with response to a specific treatment. In this post-hoc exploratory analysis, we report characteristics of pts with CR to abemaciclib+ET in M2 and M3.

Methods

M2 (NCT02107703) and M3 (NCT02246621) were double-blind, phase III studies in which women with HR+, HER2- ABC were randomised to receive abemaciclib/placebo+ET (M2: fulvestrant; M3: aromatase inhibitor). M2 included pts with progression during or ≤1 year of (neo)adjuvant ET or on first ET for ABC. M3 included pts who had not received prior systemic therapy for ABC. Disease characteristics were described in pts who achieved CR (RECIST v1.1) across the two studies, focusing on parameters reported to be associated with poor prognosis. Data are from the final progression-free survival analyses.

Results

Of 774 pts randomised to receive abemaciclib in M2 and M3, a total of 23 achieved CR: 14/446 in M2 and 9/328 in M3 (corresponding data in M2 and M3 pts receiving placebo+ET: 1/223 and 1/165 pts, respectively). A total of 3/14 M2 and 6/9 M3 abemaciclib pts had Eastern Cooperative Oncology Group (ECOG) status 1 (remainder: ECOG 0); 2/14 M2 and 0/9 M3 pts were progesterone receptor negative; 4/14 M2 and 3/9 M3 pts had a high-grade tumour; 10/14 M2 and 9/9 M3 pts had no bone-only disease, and 2/14 M2 and 0/9 M3 pts had liver metastases at baseline. Treatment-free interval was <3 years for 3/4 M3 pts with recurrent metastatic disease who had received adjuvant ET. 10/14 M2 pts and 5/9 M3 pts achieved CR <3 months after starting treatment; 7/14 M2 and 6/9 M3 pts had duration of response >15 months.

Conclusions

A small proportion of pts with recurrent ABC treated with abemaciclib in M2 and M3 achieved CR, including some pts with disease characteristics reported to be associated with poor prognosis. Those responses had a short time to onset and were relatively durable.

Editorial acknowledgement

Medical writing assistance was provided by Gill Gummer and Caroline Spencer (Rx Communications, Mold, UK).

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Funded by Eli Lilly and Company.

Disclosure

J. Huober: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Celgene; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Research grant/Funding (self): Hexal; Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Daiichi; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self): Eisai; Honoraria (self), Advisory/Consultancy: AbbVie. N. Chouaki, C. Stoffregen, A. Korfel: Full/Part-time employment: Eli Lilly and Company. F. Lerebours: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly and Company; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer. All other authors have declared no conflicts of interest.

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Presenter Of 1 Presentation

 On-Demand ePoster Display

104P - Clinical characteristics of patients (pts) with complete response (CR) to abemaciclib-based endocrine therapy (ET) in MONARCH 2 (M2) and MONARCH 3 (M3)

Abstract

Background

Abemaciclib is an oral cyclin-dependent kinase 4 & 6 inhibitor, dosed on a continuous schedule, approved for the treatment of hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) combined with ET. In this pt population, CR is rarely seen with ET alone. Pt/disease characteristics may correlate with response to a specific treatment. In this post-hoc exploratory analysis, we report characteristics of pts with CR to abemaciclib+ET in M2 and M3.

Methods

M2 (NCT02107703) and M3 (NCT02246621) were double-blind, phase III studies in which women with HR+, HER2- ABC were randomised to receive abemaciclib/placebo+ET (M2: fulvestrant; M3: aromatase inhibitor). M2 included pts with progression during or ≤1 year of (neo)adjuvant ET or on first ET for ABC. M3 included pts who had not received prior systemic therapy for ABC. Disease characteristics were described in pts who achieved CR (RECIST v1.1) across the two studies, focusing on parameters reported to be associated with poor prognosis. Data are from the final progression-free survival analyses.

Results

Of 774 pts randomised to receive abemaciclib in M2 and M3, a total of 23 achieved CR: 14/446 in M2 and 9/328 in M3 (corresponding data in M2 and M3 pts receiving placebo+ET: 1/223 and 1/165 pts, respectively). A total of 3/14 M2 and 6/9 M3 abemaciclib pts had Eastern Cooperative Oncology Group (ECOG) status 1 (remainder: ECOG 0); 2/14 M2 and 0/9 M3 pts were progesterone receptor negative; 4/14 M2 and 3/9 M3 pts had a high-grade tumour; 10/14 M2 and 9/9 M3 pts had no bone-only disease, and 2/14 M2 and 0/9 M3 pts had liver metastases at baseline. Treatment-free interval was <3 years for 3/4 M3 pts with recurrent metastatic disease who had received adjuvant ET. 10/14 M2 pts and 5/9 M3 pts achieved CR <3 months after starting treatment; 7/14 M2 and 6/9 M3 pts had duration of response >15 months.

Conclusions

A small proportion of pts with recurrent ABC treated with abemaciclib in M2 and M3 achieved CR, including some pts with disease characteristics reported to be associated with poor prognosis. Those responses had a short time to onset and were relatively durable.

Editorial acknowledgement

Medical writing assistance was provided by Gill Gummer and Caroline Spencer (Rx Communications, Mold, UK).

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Funded by Eli Lilly and Company.

Disclosure

J. Huober: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Celgene; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Research grant/Funding (self): Hexal; Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Daiichi; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self): Eisai; Honoraria (self), Advisory/Consultancy: AbbVie. N. Chouaki, C. Stoffregen, A. Korfel: Full/Part-time employment: Eli Lilly and Company. F. Lerebours: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly and Company; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer. All other authors have declared no conflicts of interest.

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