Terapia Hormonal da Paciente Premenopausa

Size: px

Start display at page:

Download "Terapia Hormonal da Paciente Premenopausa"

Alannah Golden
6 years ago
Views:

1 I Congresso de Oncologia D Or 5 e 6 de julho de 2013 Terapia Hormonal da Paciente Premenopausa Antonio C. Wolff, MD, FACP, FASCO Professor de Oncologia Programa de Câncer de Mama Johns Hopkins University School of Medicine This presentation is the intellectual property of the presenter; please contact him for permission to reprint and/or distribute

2 EBCTCG Overview on Tamoxifen 21,457 patients in 20 trials of 5y of TAM vs not - 10,645 are ER+ - Median f/u = 13y - Same effect regardless of PR status Follow-up (years) Reduction in Recurrence Rates EBCTCG, Lancet 2011

3 5y of TAM on Outcome at 15 years EBCTCG, Lancet 2011

4 Outcomes at 15y after 5y of TAM EBCTCG, Lancet 2011

5 Interaction Between Goserelin and TAM in ZIPP Trial n = 927, all premenopausal women 2 x 2 factorial design to GOS, TAM, both, or none Median follow-up 12 years Caveat unplanned subset analysis Sverrisdottir et al, BCRT 128:755, 2011

6 ZIPP Trial: First Events Drug Risk reduction Tamoxifen 27%, p = Goserelin 32%, p = Combination 24%, p = Sverrisdottir et al, BCRT 128:755, 2011

7 Effects of TAM and GOS on Time to Event Trend toward improved outcome with GOS if highly ER+? Sverrisdottir et al, BCRT 128:755, 2011

8 Menstrual Bleeding After Chemo n = 545, age Petrek et al, J Clin Oncol 24:1045, 2006

9 Very Young Women Lose ~ 2 Years of Menstrual Life After Adjuvant Chemo Age < 40 Age 40 IBCSG V and VI Percentage of women remaining premenopausal by age as treatment and treatment group Partridge et al, Eur J Cancer 43:1646, 2007

10 IBCSG Trial VIII % of Patients with Amenorrhea Age 39 Age 40 goserelin x 18 mo goserelin x 18 mo no therapy no therapy

11 Impact of Amenorrhea on Outcome in NSABP B-30 Amenorrhea vs Outcome in NSABP B30 Node-positive breast cancer n = 5258 Doxorubicin + Docetaxel (AT) Sequential ACT Concurrent ACT Sequential ACT = best DFS Swain et al, NEJM 363:2053 & 2268, 2010

12 Amenorrhea vs Outcome in NSABP B30 HR Recurrence Death ER+ 0.51* 0.52* ER Swain et al, NEJM 363:2268, 2010

13 AIs after Chemo-Induced Amenorrhea A Case Series 45 women with CIA on AIs median age 47 (range 39 52) 16 upfront, 20 switching, 9 extended 12 (27%) recovered ovarian function median time 12 months (range 4 59) menses (10), pregnancy without menses (1), and biochemical assay (1) What happens to risk of recurrence if ovarian function is stimulated by the AI? AI without ovarian suppression or without monitoring ovarian function using sensitive estradiol assays is fraught with peril in women who develop CIA! Smith et al, JCO 24:2444, 2006

14 ABCSG 12 Outcome DFS, RFS, and OS:.TAM = ANZ (left side).zol improves DFS and RFS, but not OS (right side) Gnant et al, NEJM 360:2379, 2009

ABCSG 12 after 62 months Same DFS/Worse OS with AI DFS OS 1.08 (0.81-1.44) p=0.591 1.75 (1.08-2.83) p=0.

15 ABCSG 12 after 62 months Same DFS/Worse OS with AI DFS OS 1.08 ( ) p= ( ) p=0.02 Possible reasons: Not enough events (96% still alive) No obvious differences in cause of death Chance? Methods? Obesity? Gnant et al, Lancet Oncol 12:631, 2011

16 ABCSG 12 after 62 months Worse DFS/OS with AI in Overweight/Obese Overweight vs Normal Weight Tamoxifen Anastrozole DFS 0.94 ( ) 1.60 ( ) p=0.02 OS 0.83 ( ) 2.14 ( ) p=0.01 Pfeiler et al, JCO 29:2653, 2011

17 ABCSG 12 after 62 months Worse DFS/OS with AI in Overweight/Obese Overweight vs Normal Weight Tamoxifen Anastrozole DFS 0.94 ( ) 1.60 ( ) p=0.02 OS 0.83 ( ) 2.14 ( ) p=0.01 Outcome if Treated with Anastrozole versus Tamoxifen DFS 1.49 ( ) p=0.088 Overall survival 3.03 ( ) p=0.004 Pfeiler et al, JCO 29:2653, 2011

18 Questions Faced by Premenopausal Women with ER+ Disease in late 2012 Role of TAM vs OS vs both combined? Not sure yet Is chemo-induced amenorrhea a concern? Perhaps good for cancer outcome, bad for health? Is there a role for AI plus OS? Not now Future data SOFT: 5y of TAM vs TAM/OS vs EXE/OS Closed Jan 2011, n = 3066 TEXT: 5y of TAM/OS vs EXE/OS Closed March 2011, n = 2639

19 Hormonal Therapy for the Premenopause Women ( Post ATLAS ) When to adopt 10y of TAM, based on the results of ATLAS and attom? What about women who enter in menopause with therapy (peri-menopause), what would be best to do? Prolong TAM or switch to an AI? If we have a patient who recently completed 5y of TAM, should we call them back ( recall )? Any risk profile for endometrial cancer that could guide the decision and suggest that the longer use of TAM should be avoided?

20 ATLAS Trial 2013 and beyond Davies et al,lancet epub 2 Dec 2012

21 Davies et al,lancet epub 2 Dec 2012

22 Davies et al,lancet epub 2 Dec 2012

23 Davies et al,lancet epub 2 Dec 2012

24 Davies et al,lancet epub 2 Dec 2012

27 ATLAS Trial Davies et al,lancet epub 2 Dec 2012

28 ATLAS Trial Davies et al,lancet epub 2 Dec 2012

29 Hormonal Therapy for the Premenopause Women ( Post ATLAS ) When to adopt 10y of TAM, based on the results of ATLAS and attom? What about women who enter in menopause with therapy (peri-menopause), what would be best to do? Prolong TAM or switch to an AI? If we have a patient who recently completed 5y of TAM, should we call them back ( recall )? Any risk profile for endometrial cancer that could guide the decision and suggest that the longer use of TAM should be avoided?

Extended Hormonal Therapy

Extended Hormonal Therapy Dr. Caroline Lohrisch, Medical Oncologist, BC Cancer Agency Vancouver Centre November 1, 2014 www.fpon.ca Optimal Endocrine Therapy for Women with Hormone Receptor Positive Early