- Email: [email protected]
Impact of chemotherapy-induced ovarian failure (CIOF) on disease-free survival (DFS) and overall survival (OS) in young women with early breast cancer (EBC)
abstracts
Annals of Oncology
180PD
Impact of chemotherapy-induced ovarian failure (CIOF) on diseasefree survival (DFS) and overall survival (OS) in young women with early breast cancer (EBC)
Background: Previous data has shown that chemotherapy (CT)-induced amenorrhea was associated with a better DFS and OS in premenopausal patients with EBC, regardless of the hormone-receptor status (Swain et al. NEJM 2010 ). Methods: 740 patients (pts) aged 45yrs treated with anthracycline/taxane-based CT for EBC from 4 German neo-/adjuvant trials were included. Centrally assessed estradiol and follicle-stimulating hormone (FSH) in paired blood samples collected at baseline and 4 weeks after the last therapy infusion were considered. CIOF was defined as estradiol <52.2 ng/L and FSH >12.4IU/l after CT for those pts with premenopausal hormone levels at baseline. 4-year DFS and OS (rate, hazard ratio (HR) and 95% confidence interval (CI)) overall and in subgroups by hormone-receptor status (positive, negative) and age (30, 31-35, 36-40, >40yrs) are presented. Results: Median follow-up was 49.6 (range 48.8-50.3) months. 4-year DFS and OS rates as well as HR overall and in subgroups are presented in the Table below. Pts with CIOF had a better DFS compared to pts without CIOF (HR ¼ 0.47, 95%CI 0.31-0.71). The DFS advantage was significant in pts with hormone-receptor positive (HR ¼ 0.38, 95%CI 0.22-0.64) EBC. A trend towards a better OS was observed only for pts with hormone-receptor positive EBC (HR ¼ 0.45, 95%CI 0.19-1.05). Within age groups, CIOF showed a statistically significant improvement in DFS only in women 30yrs (HR ¼ 0.21, 95%CI 0.05-0.97). No statistically significant OS benefit was observed in any of the age groups. Only pts >40yrs showed a trend towards a better OS (HR ¼ 0.35, 95%CI 0.11-1.16). Conclusions: Pts with CIOF after anthracycline/taxane-based CT for EBC show a better DFS, especially in women with hormone-receptor positive EBC or younger than 30 years. The improvement in DFS translates in a survival advantage in pts with hormonereceptor positive EBC. Legal entity responsible for the study: German Breast Group (GBG). Funding: The study was supported by Walter Schulz Stiftung. Disclosure: A. Schneeweiss: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Molecular Partner; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): MSD Oncology; Honoraria (self): Tesaro; Honoraria (self), Travel / Accommodation / Expenses: Lilly. C. Denkert: Shareholder / Stockholder / Stock options: Sividon Diagnostics; Honoraria (self): Teva; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: Daiichi Sankyo; Licensing / Royalties: VMScope digital pathology software; Licensing / Royalties: Patent application: EP18209672 - cancer immunotherapy; Licensing / Royalties: Patent application EP20150702464 - therapy response; Licensing / Royalties: Patent application EP20150702464 - therapy response. M. Untch: Honoraria (institution), Non-remunerated activity/ies: Abbvie; Honoraria (institution), Non-remunerated activity/ies: Amgen GmbH; 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), Non-remunerated activity/ies: Janssen Cilag; Honoraria (institution), Non-remunerated activity/ies: Lilly; Honoraria (institution), Non-remunerated activity/ies: MSD Merck; Honoraria (institution), Non-remunerated activity/ies: Mundipharma; Honoraria (institution), Non-remunerated activity/ ies: Myriad Genetics; Honoraria (institution), Non-remunerated activity/ies: Odonate; Honoraria (institution), Non-remunerated activity/ies: Pfizer GmbH; Honoraria (institution): PUMA Biotechnology; Honoraria (institution), Non-remunerated activity/ies: Roche Pharma AG; Honoraria (institution), Non-remunerated activity/ies: Sanofi Aventis Deutschland GmbH; Honoraria (institution), Non-remunerated activity/ies: Sividon Diagnostics; Honoraria (institution), Non-remunerated
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz240 | v57
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.006/5577895 by guest on 25 October 2019
J. Furlanetto1, V. Nekljudova1, A. Schneeweiss2, C. Thode3, C. Denkert4, M. Untch5, M. Bassy3, T. Karn6, P.A. Fasching7, E. Stickeler8, C. Schem9, F. Marme´10, E.M. Grischke11, M. van Mackelenbergh12, D. Strik13, S. Schmatloch14, V. Mu¨ller15, S. Loibl1 1 Department of Medicine and Research, German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg, Germany, 2Gynecologic Oncology, Nationales Centrum fu¨r Tumorerkrankungen Heidelberg, Heidelberg, Germany, 3Laboratoriumsmedizin, med. Mikrobiologie und Immunologie, Amedes MVZ Wagnerstibbe fu¨r Laboratoriumsmedizin, medizinische Mikrobiologie und Immunologie, Go¨ttingen, atsklinikum Marburg, Marburg, Germany, 4Institut fu¨r Pathologie UKGM, Universit€ Germany, 5Clinic for Gynecology, Gynecologic Oncology and Obstetrics, Helios Klinikum 6 atsklinikum Berlin Buch, Berlin, Germany, Labor fu¨r translationale Forschung, Universit€ Frankfurt, Frankfurt am Main, Germany, 7Department of Gynecology and Obstetrics, 8 akologie und Universit€ atsklinik Erlangen, Erlangen, Germany, Klinik fu¨r Gyn€ Geburtsmedizin, Uniklinik RWTH Aachen, Aachen, Germany, 9Mammazentrum/Op. Therapie und Onkologie, Krankenhaus Jerusalem, Hamburg, Schleswig-Holstein, Germany, 10Gynecologic Oncology, University Hospital Mannheim, Mannheim, ats Frauenklinik Tubingen, Eberhard Germany, 11Dept. fu¨r Frauengesundheit, Universit€ akologie und Geburtshilfe, Karls University, Tu¨bingen, Germany, 12Klinik fu¨r Gyn€ Schleswig-Holstein, Universit€ atsklinikum Schleswig-Holstein, Kiel, Germany, 13 Frauenheilkunde und Geburtshilfe, Endokrinologikum Berlin, Berlin, Germany, 14 Brustzentrum, Elisabeth Krankenhaus Kassel, Kassel, Germany, 15Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany
abstracts
Annals of Oncology
Table: 180PD DFS
OS
4-year rate CIOF
HR [95% CI]
no CIOF
4-year rate CIOF
no CIOF
log rank p-value
HR [95% CI]
65.0
<0.001
0.47 [0.31-0.71]
92.6
88.7
0.180
0.64 [0.33-1.23]
69.7 62.6
0.147 <0.001
0.62 [0.32-1.19] 0.38 [0.22-0.64]
88.9 95.5
89.3 88.7
0.879 0.059
0.92 [0.32-2.62] 0.45 [0.19-1.05]
69.5 59.9 63.5 65.0
0.027 0.099 0.119 0.207
0.21 [0.05-0.97] 0.49 [0.21-1.16] 0.54 [0.25-1.18] 0.53 [0.19-1.45]
95.7 92.2 92.7 92.4
90.8 96.3 84.9 81.3
0.286 0.945 0.431 0.072
0.31 [0.03-3.00] 1.06 [0.22-5.15] 0.61 [0.17-2.13] 0.35 [0.11-1.16]
activity/ies: TEVA Pharmaceuticals Ind Ltd; Honoraria (institution), Non-remunerated activity/ies: Novartis. P.A. Fasching: Honoraria (self), Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Biontech; Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Celgene; Honoraria (self): Daiichi-Sankyo; Honoraria (self): TEVA; Honoraria (self): AstraZeneca; Honoraria (self): Merck Sharp & Dohme; Honoraria (self): Myelo Therapeutics; Honoraria (self): Macrogenics; Honoraria (self): Eisai; Honoraria (self): PUMA; Research grant / Funding (institution): Cepheid. F. Marme´: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Tesaro; Honoraria (self): Novartis; Honoraria (self): Amgen; Honoraria (self): PharmaMar; Honoraria (self): GenomicHealth; Honoraria (self): CureVac; Honoraria (self): EISAI; Honoraria (self): Clovis; Honoraria (self): Celgene. M. van Mackelenbergh: Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Amgen. V. Mu¨ller: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgem; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Diichi-Sankyo; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (self), Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Honoraria (self), Speaker Bureau / Expert testimony: Celgene; Honoraria (self), Speaker Bureau / Expert testimony: Teva; Honoraria (self), Speaker Bureau / Expert testimony: Janssen-Cilag; Honoraria (self), Advisory / Consultancy: Genomic Health; Honoraria (self), Advisory / Consultancy: Hexal; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: Nektar; Research grant / Funding (institution): Seattle Genetics. S. Loibl: Research grant / Funding (institution): Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Teva; Research grant / Funding (institution): Vifor; Research grant / Funding (institution): PRIME; Research grant / Funding (institution): Daiichi; Licensing / Royalties: EP14153692.0 pending. All other authors have declared no conflicts of interest.
v58 | Breast Cancer, Early Stage
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.006/5577895 by guest on 25 October 2019
overall (n ¼ 740) 84.4 hormone-receptor status negative (n ¼ 315) 79.9 positive (n ¼ 425) 87.8 age (years) 30 (n ¼ 62) 92.8 31-35 (n ¼ 100) 80.4 36-40 (n ¼ 205) 81.8 >40 (n ¼ 373) 85.7
log rank p-value
Annals of Oncology
180PD
Impact of chemotherapy-induced ovarian failure (CIOF) on diseasefree survival (DFS) and overall survival (OS) in young women with early breast cancer (EBC)
Background: Previous data has shown that chemotherapy (CT)-induced amenorrhea was associated with a better DFS and OS in premenopausal patients with EBC, regardless of the hormone-receptor status (Swain et al. NEJM 2010 ). Methods: 740 patients (pts) aged 45yrs treated with anthracycline/taxane-based CT for EBC from 4 German neo-/adjuvant trials were included. Centrally assessed estradiol and follicle-stimulating hormone (FSH) in paired blood samples collected at baseline and 4 weeks after the last therapy infusion were considered. CIOF was defined as estradiol <52.2 ng/L and FSH >12.4IU/l after CT for those pts with premenopausal hormone levels at baseline. 4-year DFS and OS (rate, hazard ratio (HR) and 95% confidence interval (CI)) overall and in subgroups by hormone-receptor status (positive, negative) and age (30, 31-35, 36-40, >40yrs) are presented. Results: Median follow-up was 49.6 (range 48.8-50.3) months. 4-year DFS and OS rates as well as HR overall and in subgroups are presented in the Table below. Pts with CIOF had a better DFS compared to pts without CIOF (HR ¼ 0.47, 95%CI 0.31-0.71). The DFS advantage was significant in pts with hormone-receptor positive (HR ¼ 0.38, 95%CI 0.22-0.64) EBC. A trend towards a better OS was observed only for pts with hormone-receptor positive EBC (HR ¼ 0.45, 95%CI 0.19-1.05). Within age groups, CIOF showed a statistically significant improvement in DFS only in women 30yrs (HR ¼ 0.21, 95%CI 0.05-0.97). No statistically significant OS benefit was observed in any of the age groups. Only pts >40yrs showed a trend towards a better OS (HR ¼ 0.35, 95%CI 0.11-1.16). Conclusions: Pts with CIOF after anthracycline/taxane-based CT for EBC show a better DFS, especially in women with hormone-receptor positive EBC or younger than 30 years. The improvement in DFS translates in a survival advantage in pts with hormonereceptor positive EBC. Legal entity responsible for the study: German Breast Group (GBG). Funding: The study was supported by Walter Schulz Stiftung. Disclosure: A. Schneeweiss: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Molecular Partner; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): MSD Oncology; Honoraria (self): Tesaro; Honoraria (self), Travel / Accommodation / Expenses: Lilly. C. Denkert: Shareholder / Stockholder / Stock options: Sividon Diagnostics; Honoraria (self): Teva; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: Daiichi Sankyo; Licensing / Royalties: VMScope digital pathology software; Licensing / Royalties: Patent application: EP18209672 - cancer immunotherapy; Licensing / Royalties: Patent application EP20150702464 - therapy response; Licensing / Royalties: Patent application EP20150702464 - therapy response. M. Untch: Honoraria (institution), Non-remunerated activity/ies: Abbvie; Honoraria (institution), Non-remunerated activity/ies: Amgen GmbH; 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), Non-remunerated activity/ies: Janssen Cilag; Honoraria (institution), Non-remunerated activity/ies: Lilly; Honoraria (institution), Non-remunerated activity/ies: MSD Merck; Honoraria (institution), Non-remunerated activity/ies: Mundipharma; Honoraria (institution), Non-remunerated activity/ ies: Myriad Genetics; Honoraria (institution), Non-remunerated activity/ies: Odonate; Honoraria (institution), Non-remunerated activity/ies: Pfizer GmbH; Honoraria (institution): PUMA Biotechnology; Honoraria (institution), Non-remunerated activity/ies: Roche Pharma AG; Honoraria (institution), Non-remunerated activity/ies: Sanofi Aventis Deutschland GmbH; Honoraria (institution), Non-remunerated activity/ies: Sividon Diagnostics; Honoraria (institution), Non-remunerated
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz240 | v57
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.006/5577895 by guest on 25 October 2019
J. Furlanetto1, V. Nekljudova1, A. Schneeweiss2, C. Thode3, C. Denkert4, M. Untch5, M. Bassy3, T. Karn6, P.A. Fasching7, E. Stickeler8, C. Schem9, F. Marme´10, E.M. Grischke11, M. van Mackelenbergh12, D. Strik13, S. Schmatloch14, V. Mu¨ller15, S. Loibl1 1 Department of Medicine and Research, German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg, Germany, 2Gynecologic Oncology, Nationales Centrum fu¨r Tumorerkrankungen Heidelberg, Heidelberg, Germany, 3Laboratoriumsmedizin, med. Mikrobiologie und Immunologie, Amedes MVZ Wagnerstibbe fu¨r Laboratoriumsmedizin, medizinische Mikrobiologie und Immunologie, Go¨ttingen, atsklinikum Marburg, Marburg, Germany, 4Institut fu¨r Pathologie UKGM, Universit€ Germany, 5Clinic for Gynecology, Gynecologic Oncology and Obstetrics, Helios Klinikum 6 atsklinikum Berlin Buch, Berlin, Germany, Labor fu¨r translationale Forschung, Universit€ Frankfurt, Frankfurt am Main, Germany, 7Department of Gynecology and Obstetrics, 8 akologie und Universit€ atsklinik Erlangen, Erlangen, Germany, Klinik fu¨r Gyn€ Geburtsmedizin, Uniklinik RWTH Aachen, Aachen, Germany, 9Mammazentrum/Op. Therapie und Onkologie, Krankenhaus Jerusalem, Hamburg, Schleswig-Holstein, Germany, 10Gynecologic Oncology, University Hospital Mannheim, Mannheim, ats Frauenklinik Tubingen, Eberhard Germany, 11Dept. fu¨r Frauengesundheit, Universit€ akologie und Geburtshilfe, Karls University, Tu¨bingen, Germany, 12Klinik fu¨r Gyn€ Schleswig-Holstein, Universit€ atsklinikum Schleswig-Holstein, Kiel, Germany, 13 Frauenheilkunde und Geburtshilfe, Endokrinologikum Berlin, Berlin, Germany, 14 Brustzentrum, Elisabeth Krankenhaus Kassel, Kassel, Germany, 15Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany
abstracts
Annals of Oncology
Table: 180PD DFS
OS
4-year rate CIOF
HR [95% CI]
no CIOF
4-year rate CIOF
no CIOF
log rank p-value
HR [95% CI]
65.0
<0.001
0.47 [0.31-0.71]
92.6
88.7
0.180
0.64 [0.33-1.23]
69.7 62.6
0.147 <0.001
0.62 [0.32-1.19] 0.38 [0.22-0.64]
88.9 95.5
89.3 88.7
0.879 0.059
0.92 [0.32-2.62] 0.45 [0.19-1.05]
69.5 59.9 63.5 65.0
0.027 0.099 0.119 0.207
0.21 [0.05-0.97] 0.49 [0.21-1.16] 0.54 [0.25-1.18] 0.53 [0.19-1.45]
95.7 92.2 92.7 92.4
90.8 96.3 84.9 81.3
0.286 0.945 0.431 0.072
0.31 [0.03-3.00] 1.06 [0.22-5.15] 0.61 [0.17-2.13] 0.35 [0.11-1.16]
activity/ies: TEVA Pharmaceuticals Ind Ltd; Honoraria (institution), Non-remunerated activity/ies: Novartis. P.A. Fasching: Honoraria (self), Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Biontech; Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Celgene; Honoraria (self): Daiichi-Sankyo; Honoraria (self): TEVA; Honoraria (self): AstraZeneca; Honoraria (self): Merck Sharp & Dohme; Honoraria (self): Myelo Therapeutics; Honoraria (self): Macrogenics; Honoraria (self): Eisai; Honoraria (self): PUMA; Research grant / Funding (institution): Cepheid. F. Marme´: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Tesaro; Honoraria (self): Novartis; Honoraria (self): Amgen; Honoraria (self): PharmaMar; Honoraria (self): GenomicHealth; Honoraria (self): CureVac; Honoraria (self): EISAI; Honoraria (self): Clovis; Honoraria (self): Celgene. M. van Mackelenbergh: Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Amgen. V. Mu¨ller: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgem; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Diichi-Sankyo; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (self), Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Honoraria (self), Speaker Bureau / Expert testimony: Celgene; Honoraria (self), Speaker Bureau / Expert testimony: Teva; Honoraria (self), Speaker Bureau / Expert testimony: Janssen-Cilag; Honoraria (self), Advisory / Consultancy: Genomic Health; Honoraria (self), Advisory / Consultancy: Hexal; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: Nektar; Research grant / Funding (institution): Seattle Genetics. S. Loibl: Research grant / Funding (institution): Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Teva; Research grant / Funding (institution): Vifor; Research grant / Funding (institution): PRIME; Research grant / Funding (institution): Daiichi; Licensing / Royalties: EP14153692.0 pending. All other authors have declared no conflicts of interest.
v58 | Breast Cancer, Early Stage
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.006/5577895 by guest on 25 October 2019
overall (n ¼ 740) 84.4 hormone-receptor status negative (n ¼ 315) 79.9 positive (n ¼ 425) 87.8 age (years) 30 (n ¼ 62) 92.8 31-35 (n ¼ 100) 80.4 36-40 (n ¼ 205) 81.8 >40 (n ¼ 373) 85.7
log rank p-value