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Is there a State-of-the-art EndocrineTherapy for ER+ HER2- MBC?                  Olivia Pagani                    Institut...
“Mostly” agreed indications• Luminal A and B MBC• Indolent disease (RFI)• Low tumour burden/oligosymptomatic              ...
Complex scenarios1.1°-line ET2.2° line ET3.Beyond the 2° line…(no man’s land…)4.Postmenopausal  Pre and perimenopausal• Pa...
First-line AIs Versus Tamoxifen  in Postmenopausal women
ORRSignificant difference in favouring AIs over TAMORR (OR, 1.56; 95% CI, 1.17-2.07; P .002) andCB (OR, 1.70; 95% CI, 1.24...
OSTrend toward an improved OS not significant(OR, 1.95; 95% CI, 0.88-4.30; P .10).             Hong-Bin Xu et al Clinical ...
Are all the AIs the same?
No significant differencesin clinical activity                             103 pts
What aboutFulvestrant?
FIRST: Study design                       Randomization (1:1), open-label first-                     line ER+ postmenopaus...
FIRST: Fulvestrant 500 mg vs            anastrozole as 1°-line therapy                                       1.0          ...
FIRST: Response to first subsequent               endocrine therapy                                                 No. (%...
2° line therapy
AI as 2°-line therapy• Significant benefit in terms of  OS (HR 0.80, 95% CI 0.66 to 0.96)• But not for  PFS (HR 1.08, 95%C...
28 patients
Relapse on adjuvantET or within 1 yearfrom completion ofadjuvant ETRelapse >1 year fromcompletion ofadjuvant ET orde novo ...
Statistically significant increase in PFS   No crossover yet to the higher dose
Premenopausal women
ANA +LH-RH   TAM +LH-RH   P-value        Monica Castiglione ESM0 2011
1°-Line Phase II Parallel Group Study           Premenopausal MBC Pts Treated With Letrozole Plus Goserelin andPostmenopau...
Beyond the 2° line….
Is it worthwhile?• New drugs and approaches!  Trials needed!• When switching to CT?• When “only” palliative care?• Old dru...
Pharmaco-economics      Cost of 6 months’ therapy with:• Tamoxifen                     75 Eu• Megace                      ...
Conclusions• No “universal” standards• Many questions still open• Patients’ preferences• QoL issues underscored• New endpo...
Thank you
ABC1 - O. Pagani - State-of-the-art HT treatment in ER+ disease
ABC1 - O. Pagani - State-of-the-art HT treatment in ER+ disease
ABC1 - O. Pagani - State-of-the-art HT treatment in ER+ disease
ABC1 - O. Pagani - State-of-the-art HT treatment in ER+ disease
ABC1 - O. Pagani - State-of-the-art HT treatment in ER+ disease
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ABC1 - O. Pagani - State-of-the-art HT treatment in ER+ disease

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Transcript of "ABC1 - O. Pagani - State-of-the-art HT treatment in ER+ disease "

  1. 1. Is there a State-of-the-art EndocrineTherapy for ER+ HER2- MBC? Olivia Pagani Institute of Oncology of Southern Switzerland
  2. 2. “Mostly” agreed indications• Luminal A and B MBC• Indolent disease (RFI)• Low tumour burden/oligosymptomatic Pitfalls• Change in hormone expression• Non homogeneous population: Patients relapsing after Adj Tam (so few?) Patients relapsing after Adj TAM and AIs• Endpoints/subsequent therapies
  3. 3. Complex scenarios1.1°-line ET2.2° line ET3.Beyond the 2° line…(no man’s land…)4.Postmenopausal Pre and perimenopausal• Patients relapsing under Adj ET Intrinsic/acquired resistance• Role and timing of Chemotherapy
  4. 4. First-line AIs Versus Tamoxifen in Postmenopausal women
  5. 5. ORRSignificant difference in favouring AIs over TAMORR (OR, 1.56; 95% CI, 1.17-2.07; P .002) andCB (OR, 1.70; 95% CI, 1.24-2.33; P .0009) Hong-Bin Xu et al Clinical Breast Cancer 11 (4); 246, 2011
  6. 6. OSTrend toward an improved OS not significant(OR, 1.95; 95% CI, 0.88-4.30; P .10). Hong-Bin Xu et al Clinical Breast Cancer 11 (4); 246, 2011
  7. 7. Are all the AIs the same?
  8. 8. No significant differencesin clinical activity 103 pts
  9. 9. What aboutFulvestrant?
  10. 10. FIRST: Study design Randomization (1:1), open-label first- line ER+ postmenopausal patients with advanced breast cancer (target, n=200; actual, n=205) Endpoints at primary DCO Primary endpoint  Clinical benefit rate Secondary endpoints Fulvestrant 500 mg Anastrozole 1 mg  Objective response rate (500 mg IM on Days (1 mg PO daily)  Time to progression 0, 14, and 28, and every 28  Duration of response days thereafter)  Duration of clinical benefit  Safety Exploratory endpoints Progression Progression  Best response to subsequent therapy Follow-up Follow-up No Prior ET for ABC Adj ET ≥ 12 monthsDCO = data cut-off Robertson JF et al. Cancer Res 2010;70(24 Suppl): abstract S1-3
  11. 11. FIRST: Fulvestrant 500 mg vs anastrozole as 1°-line therapy 1.0 Significantly longer TTP Proportion of patients alive 0.8 and progression-free Fulvestrant 500 mg Anastrozole 1 mg 0.6 0.4 0.2 HR = 0.66 (95% CI: 0.47–0.92) P = 0.01 0.0 0 6 12 18 24 30 36 42 48 Time (months)No. at risk:Fulvestrant 500 mg 102 74 65 52 45 34 20 6 0Anastrozole 1 mg 103 69 55 39 30 21 8 2 0 Robertson JF et al. JCO 2009 27:4530
  12. 12. FIRST: Response to first subsequent endocrine therapy No. (%) of patients Fulvestrant AnastrozoleNo. of patients who progressed 63 79Patients who received subsequent 34 50endocrine breast cancer therapy Complete response 0 0 Partial response 3 (8.8) 7 (14.0) Total responders 3 (8.8) 7 (14.0) Stable disease ≥24 weeks 11 (32.4) 14 (28.0) Total with clinical benefit 14 (41.2) 21 (42.0) Stable disease <24 weeks 10 (29.4) 16 (32.0) Progressive disease 3 (8.8) 8 (16.0) Not evaluable 7 (20.6) 5 (10.0) Robertson JF et al. Cancer Res 2010;70(24 Suppl): abstract S1-3
  13. 13. 2° line therapy
  14. 14. AI as 2°-line therapy• Significant benefit in terms of OS (HR 0.80, 95% CI 0.66 to 0.96)• But not for PFS (HR 1.08, 95%CI 0.89 to 1.31) CB (OR 1.00, 95% CI 0.87 to 1.14) OR (OR 0.96, 95% CI 0.81 to 1.14).• This is difficult to interpret due to the extreme heterogeneity across AIs for PFS but not the other endpoints. Cochrane Database Syst Rev. 2007
  15. 15. 28 patients
  16. 16. Relapse on adjuvantET or within 1 yearfrom completion ofadjuvant ETRelapse >1 year fromcompletion ofadjuvant ET orde novo MBCafter 1° line with eitheran antiestrogen or AI
  17. 17. Statistically significant increase in PFS No crossover yet to the higher dose
  18. 18. Premenopausal women
  19. 19. ANA +LH-RH TAM +LH-RH P-value Monica Castiglione ESM0 2011
  20. 20. 1°-Line Phase II Parallel Group Study Premenopausal MBC Pts Treated With Letrozole Plus Goserelin andPostmenopausal Pts Treated With Letrozole TTP (P .89) OS (P .76) 73 patients overall In Hae Park, JCO 28:2705, 2010
  21. 21. Beyond the 2° line….
  22. 22. Is it worthwhile?• New drugs and approaches! Trials needed!• When switching to CT?• When “only” palliative care?• Old drugs: High dose AIs Megestrol acetate High dose estrogens• QoL issues!
  23. 23. Pharmaco-economics Cost of 6 months’ therapy with:• Tamoxifen 75 Eu• Megace 400 Eu• Anastrozole 1.025 Eu• Letrozole 1.043 Eu• Exemestane 1.050 Eu• Fulvestrant 250mg 3.762 Eu Prue Francis Berlin 2010
  24. 24. Conclusions• No “universal” standards• Many questions still open• Patients’ preferences• QoL issues underscored• New endpoints important in indolent disease• Integration with supportive care
  25. 25. Thank you

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