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San Antonio Breast Cancer - PowerPoint Presentation

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San Antonio Breast Cancer - PPT Presentation

Symposium December 59 2017 This presentation is the intellectual property of the author presenter Contact them at matteolambertinibordetbe for ID: 800426

breast cancer matteo lambertini cancer breast lambertini matteo 2017 bordet san symposium antonio december presentation intellectual property presenter contact

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Slide1

San Antonio Breast Cancer Symposium, December 5-9, 2017

This presentation is the intellectual property of the author/presenter. Contact them at matteo.lambertini@bordet.be for permission to reprint and/or distribute

Pooled analysis of five randomized trials investigating temporary ovarian suppression with gonadotropin-releasing hormone analogs during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal early breast cancer patients

Matteo Lambertini1, Halle C.F. Moore2, Robert C.F. Leonard3, Sibylle Loibl4, Pamela Munster5, Marco Bruzzone6, Luca Boni7, Joseph M. Unger8, Richard A. Anderson9, Keyur Mehta4, Susan Minton10, Francesca Poggio6, Kathy S. Albain11, Douglas J.A. Adamson12, Bernd Gerber13, Amy Cripps14, Gianfilippo Bertelli15, Sabine Seiler4, Marcello Ceppi6, Ann H. Partridge16, and Lucia Del Mastro6

1

Institut Jules

Bordet

and

Université

Libre de Bruxelles (U.L.B.),

Brussels

,

Belgium

.

2

Cleveland Clinic Foundation,

Taussig

Cancer

Institute

, Cleveland, OH.

3

Imperial College, London, UK.

4

GBG -

German

Breast

Group

,

Neu-Isenburg

,

Germany.

5

UCSF - University of California, San Francisco, CA.

6

Ospedale Policlinico San Martino-IST, Genova,

Italy

.

7

AOU Careggi and Istituto Toscano Tumori, Firenze,

Italy

.

8

SWOG Statistical Center, Fred

Hutchinson

Cancer

Research

Center, Seattle, WA

.

9

MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.

10

Moffitt Cancer Center, Tampa, FL.

11

Loyola

University

Medical

Center, Cardinal

Bernardin

Cancer

Center,

Maywood

, IL.

12

Tayside

Cancer Centre,

Ninewells

Hospital, Dundee, UK.

13

University Hospital Rostock, Rostock, Germany.

14

Nexgen

Oncology, Dallas, TX.

15

Singleton Hospital, Swansea, UK.

16

D

ana-

Farber

Cancer

Institute

, Boston, MA.

Slide2

San Antonio Breast Cancer Symposium, December 5-9, 2017

This presentation is the intellectual property of the author/presenter. Contact them at matteo.lambertini@bordet.be for permission to reprint and/or distribute

DisclosuresLambertini Matteo:Consultant or advisor: TevaTravel grant: Astellas

Slide3

San Antonio Breast Cancer Symposium, December 5-9, 2017

This presentation is the intellectual property of the author/presenter. Contact them at matteo.lambertini@bordet.be for permission to reprint and/or distribute

“Fertility preservation and pregnancy-related issues are high priority areas of concern for young women with breast cancer”Paluch-Shimon S et al, Breast 2017;35:203-17Background

Slide4

San Antonio Breast Cancer Symposium, December 5-9, 2017

This presentation is the intellectual property of the author/presenter. Contact them at matteo.lambertini@bordet.be for permission to reprint and/or distribute

BackgroundPremature ovarian insufficiency (POI) is a common side effect of chemotherapy in premenopausal patients with substantial negative impact on their quality of lifeOocyte/embryo cryopreservation are standard strategies for fertility preservation but they do not prevent the risk of chemotherapy-induced POITemporary ovarian suppression with GnRHa during chemotherapy has been studied in several RCTs as a strategy to preserve ovarian

function and potential fertilityHowever, data are mixed and its role remains controversialPaluch-Shimon S et al, Breast 2017;35:203-17. Loren AW et al, J Clin Oncol 2013;31:2500-10. Peccatori F et al, Ann Oncol 2013;24 Suppl 6;vi160-70. Lambertini M et al, Ann Oncol 2015;26:2408-19. Lambertini M et al, Eur J Cancer 2017;71:25-33.

Slide5

San Antonio Breast Cancer Symposium, December 5-9, 2017

This presentation is the intellectual property of the author/presenter. Contact them at matteo.lambertini@bordet.be for permission to reprint and/or distribute

Study Objectives and EndpointsSystematic review and meta-analysis of individual patient data from RCTs to evaluate the efficacy (ovarian function and fertility preservation) and the safety (survival outcomes) of GnRHa use during chemotherapy Primary endpointsPOI rate (according to the definition used as primary endpoint in each trial)Post-treatment pregnancy rateSecondary endpointsAmenorrhea rates one year and two years after the end of chemotherapyDisease-free survival (DFS) and overall

survival (OS)

Slide6

San Antonio Breast Cancer Symposium, December 5-9, 2017

This presentation is the intellectual property of the author/presenter. Contact them at matteo.lambertini@bordet.be for permission to reprint and/or distribute

Study CharacteristicsPROMISE-GIM61,2POEMS/SWOG S02303Moffitt-led trial4GBG-37 ZORO5Anglo Celtic Group OPTION6Definition of POI

No resumption of menstrual activity and postmenopausal levels of FSH and E2Amenorrhea for the prior 6 months and postmenopausal levels of FSHNo maintenance of menses and no resumption of mensesNo re-appearance of two consecutive menstrual periods within 21 to 35 daysAmenorrhea with elevated FSHTiming of POI after chemotherapy12 months24 months24 months6 monthsBetween 12 and 24 monthsSample size2812574860227ER status for eligibility

ER-positive and ER-negative

ER-negative only

ER-positive and ER-negative

ER-negative only

ER-positive and ER-negative

Upper age limit for eligibility

≤ 45 years

≤ 49 years

≤ 44 years

≤ 45 years

None

Type

of

GnRHa

Triptorelin

Goserelin

Triptorelin

Goserelin

Goserelin

1. Del Mastro L et al,

JAMA

2011;306:269-76. 2. Lambertini M et al,

JAMA

2015;314:2632-40. 3. Moore HCF et al,

N Engl J Med 2015;372:923-32. 4. Munster P et al, J Clin Oncol 2012;30:533-38. 5. Gerber B et al, J Clin Oncol 2011;29:2334-41. 6. Leonard RCF et al, Ann Oncol 2017;28:1811-16.

Slide7

San Antonio Breast Cancer Symposium, December 5-9, 2017

This presentation is the intellectual property of the author/presenter. Contact them at matteo.lambertini@bordet.be for permission to reprint and/or distribute

Baseline CharacteristicsGnRHa group(n=436)No. (%)Control group(n=437)No. (%)p value* Age, median (interquartile range), years38 (34-42)39 (35-42)0.258

Age distribution, years≤ 40≥ 41 297 (68.1) 139 (31.9) 283 (64.8) 154 (35.2)0.316 Estrogen receptor statusPositive NegativeMissing177 (40.6)257 (58.9)2 (0.5)173 (39.6)262 (59.9)2 (0.5)0.782

Type of chemotherapy

Anthracycline only-based

Anthracycline- and

taxane

-based

Non anthracycline-based

Missing

194 (44.5)

227 (52.1)

6 (1.4)

9 (2.1)

198 (45.3)

210 (48.0)

13 (3.0)

16 (3.7)

0.196

Cumulative cyclophosphamide dose

, median (

interquartile range

), mg/m

2

4000 (3420

-5185)

3960 (3082-5400)0.585*Calculated by excluding missing data

Slide8

San Antonio Breast Cancer Symposium,

December 5-9, 2017This presentation is the intellectual property of the author/presenter. Contact them at matteo.lambertini@bordet.be for permission to reprint and/or

distribute Premature-Ovarian Insufficiency Rate14.1%GnRHa groupn=363 Control groupn=359 30.9%OR* 0.38 (95% CI 0.26-0.57)p<0.001 Subgroup analysis*Odds ratio (OR) adjusted for age, estrogen receptor status, type and duration of chemotherapy

administered

Slide9

San Antonio Breast Cancer Symposium, December 5-9, 2017

This presentation is the intellectual property of the author/presenter. Contact them at matteo.lambertini@bordet.be for permission to reprint and/or distribute

Amenorrhea Rates36.8%GnRHa groupn=386 Control groupn=374 40.4%OR* 0.92 (95% CI 0.66-1.28); p=0.623 18.2%GnRHa groupn=214 Control groupn

=21030.0%OR* 0.51 (95% CI 0.31-0.85); p=0.009One-Year AmenorrheaTwo-Year Amenorrhea*Odds ratio (OR) adjusted for age, estrogen receptor status, type and duration of chemotherapy administered

Slide10

San Antonio Breast Cancer Symposium, December 5-9, 2017

This presentation is the intellectual property of the author/presenter. Contact them at matteo.lambertini@bordet.be for permission to reprint and/or distribute

Post-Treatment Pregnancy RateGnRHa Group: 37/359 (10.3%)vs.Control Group: 20/367 (5.5%)IRR* 1.83 (95% CI 1.06-3.15)p=0.030 GnRHa group(n = 37)No. (%)Control group(n = 20)No. (%)Age distribution, years≤ 40

≥ 41 37 (100)0 (0.0) 20 (100)0 (0.0)Estrogen receptor status PositiveNegative 6 (16.2)31 (83.8) 2 (10.0)18 (90.0)*Incidence rate ratio (IRR)

Slide11

Disease-free survivalOverall survivalSan Antonio

Breast Cancer Symposium, December 5-9, 2017This presentation is the intellectual property of the author/presenter. Contact them

at matteo.lambertini@bordet.be for permission to reprint and/or distribute Survival Outcomes*Hazard ratio (HR) adjusted for age, estrogen receptor status, type and duration of chemotherapy administered and tumor stage HR* 1.01 (95% CI 0.72-1.42)p=0.999 HR* 0.67 (95% CI 0.42-1.06)p=0.083

Slide12

San Antonio Breast Cancer Symposium, December 5-9, 2017

This presentation is the intellectual property of the author/presenter. Contact them at matteo.lambertini@bordet.be for permission to reprint and/or distribute

ConclusionsAdministration of GnRHa during chemotherapy was associated with a significant reduction in the risk of chemotherapy-induced POIA greater number of women in the GnRHa group had a post-treatment pregnancySimilar DFS and OS were observed between groups irrespective of the estrogen receptor status of the diseaseThis strategy should be considered as an option to reduce the likelihood of chemotherapy-induced POI and potentially improve future fertility in premenopausal early breast cancer patients undergoing (neo)

adjuvant chemotherapy

Slide13

San Antonio Breast Cancer Symposium, December 5-9, 2017

This presentation is the intellectual property of the author/presenter. Contact them at matteo.lambertini@bordet.be for permission to reprint and/or distribute

AcknowledgmentsAll the patients enrolled in the trials and their familiesAll the investigators and research teamsThe Gruppo Italiano Mammella (GIM) study group, the SWOG, the Anglo Celtic Group and the German Breast GroupItalian Association for Cancer Research (AIRC) for supplemental funding

Slide14

San Antonio Breast Cancer Symposium, December 5-9, 2017

This presentation is the intellectual property of the author/presenter. Contact them at matteo.lambertini@bordet.be for permission to reprint and/or distribute

AcknowledgmentsEuropean Society for Medical Oncology (ESMO) for a Translational Research Fellowship at Institut Jules Bordet (Brussels, Belgium)San Antonio Breast Cancer Symposium (SABCS) Scientific Committee for a SABCS Clinical Scholar Award