Download to read offline
Uploaded byONCOcare
22 atualização tratamento sistêmico
This document summarizes results from several clinical trials testing different treatments for HER2-negative metastatic breast cancer. Key findings include: 1) A phase III study found that maintenance treatment with paclitaxel and gemcitabine after first-line paclitaxel/gemcitabine significantly prolonged progression-free survival compared to observation alone. Overall survival was also significantly prolonged with maintenance therapy. 2) Another study found fulvestrant 500 mg was superior to anastrozole in patients with advanced breast cancer who had relapsed or progressed on prior tamoxifen therapy. Progression-free survival was longer with fulvestrant. 3) The BOLERO-2 trial
More Related Content
Similar to 22 atualização tratamento sistêmico
22 atualização tratamento sistêmico
- 1. HER2 negativo AtualizaçãoTratamento Sistêmico
- 2. Tratamento da DoençaMetastática QT Doença Metastática Paclitaxel vs Nab-Paclitaxel vs Ixabepilona Manutenção (?) Hormonioterapia Faslodex na primeira linha Everolimus Duplo bloqueio hormonal (?)
- 3. Tratamento da DoençaMetastática QT Doença Metastática Paclitaxel vs Nab-Paclitaxel vs Ixabepilona
- 4. CALGB 40502: BevacizumabPlus Nab- Pac, Ixabepilone, or Pac in Untreated MBC Stratified by receipt of adjuvant taxanes Disease progression† and HR status Paclitaxel 90 mg/m2/wk + Bevacizumab* 10 mg/kg q2w (n = 283) Treatment-naive patients Nab-paclitaxel 150 mg/m2/wk + with locally recurrent or Bevacizumab* 10 mg/kg q2w metastatic breast cancer (n = 271) (N = 799) Ixabepilone 16 mg/m2/wk + Bevacizumab* 10 mg/kg q2w (n = 245) Note: All chemotherapy given for 3 wks on, 1 wk off. *Protocol amended in March 2011 (n = 669) to allow optional use of bevacizumab following ODAC recommendation that approval be withdrawn for metastatic breast cancer; 98% of all patients received bevacizumab. †Patients with SD or responding disease after 6 cycles could discontinue chemotherapy and continue bevacizumab alone. Rugo HS, et al. ASCO 2012. Abstract CRA1002.
- 5. Bevacizumab Plus Nab-Pac,Ixabepilone, or Paclitaxel in MBC: Interim Monitoring First interim PFS analysis (165 events) – Ixabepilone vs paclitaxel crossed superiority futility boundary – Accrual to ixabepilone arm closed July 2011 Second interim PFS analysis (236 events) – Nab-paclitaxel vs paclitaxel crossed superiority futility boundary – Study closed November 2011 Rugo HS, et al. ASCO 2012. Abstract CRA1002.
- 6. Nab-Paclitaxel vs Ixabepilonein MBC: Survival Not Improved vs Paclitaxel PFS OS Comparison HR P Value 95% CI Comparison HR P Value 95% CI Nab vs Pac 1.19 .12 0.96-1.49 Nab vs Pac 1.02 .92 0.75-1.38 Ixa vs Pac 1.53 < .0001 1.24-1.90 Ixa vs Pac 1.28 .10 0.95-1.72 1 1 Proportion Progression Free 0.8 0.8 Proportion Alive Paclitaxel Nab-paclitaxel 0.6 0.6 Ixabepilone 0.4 0.4 Paclitaxel Nab-paclitaxel 0.2 0.2 Ixabepilone 0 0 0 10 20 30 0 10 20 30 Mos Mos Rugo HS, et al. ASCO 2012. Abstract CRA1002. Used with permission.
- 7. Nab-Paclitaxel vs Ixabepilonein MBC: More Discontinuation vs Paclitaxel 60 50 Paclitaxel Discontinued (%) Nab-paclitaxel 40 Ixabepilone 30 20 10 0 1 2 3 4 5 Cycle number 45% dose reductions with nab-paclitaxel by cycle 3 compared with 15% for both ixabepilone and paclitaxel Rugo HS, et al. ASCO 2012. Abstract CRA1002. Used with permission.
- 8. Nab-Paclitaxel vs Ixabepilonein MBC: Worse Toxicities vs Paclitaxel P = .004 P = .005 90 P < .0001 P = .0002 Nab-paclitaxel (n = 258) 79 Grade ≥ 3 Adverse Event (%) 80 Paclitaxel (n = 262) 70 Ixabepilone (n 237) 59 60 60 55 56 51 50 44 40 30 21 20 12 10 0 Any Hematologic Nonhematologic Rugo HS, et al. ASCO 2012. Abstract CRA1002. Used with permission.
- 9. Nab-Paclitaxel vs Ixabepilonevs Paclitaxel in MBC: Adverse Events Grade 3/4 Adverse Event, % Nab-Paclitaxel Paclitaxel Ixabepilone (n = 258) (n = 262) (n = 237) Leukopenia 17 (P = .0004) 7 3 (P = .042) Neutropenia 47 (P = .0001) 18 7 (P = .0002) Hypertension 7 8 11 Fatigue 16 (P = .010) 9 15 (P = .036) Pain 10 (P = .010) 4 4 Neuropathy Motor 10 (P = .0003) 2 6 (P = .021) Sensory 25 (P = .012) 16 25 (P = .022) • Grade 3 24 16 22 • Grade 4 1 <1 3 Rugo HS, et al. ASCO 2012. Abstract CRA1002. Used with permission.
- 10. Tratamento da DoençaMetastática QT Doença Metastática Paclitaxel vs Nab-Paclitaxel vs Ixabepilona Manutenção (?)
- 11. Phase III Study:Maintenance vs Obs in MBC with Response to First-line Pac/Gem Stratified by visceral disease, prior adjuvant taxane, response (CR/PR vs SD), HR status Maintenance Paclitaxel and Gemcitabine* until progression Patients with (n = 116) MBC and CR, PR, or SD to 6 cycles first-line paclitaxel/gemcitabine* (N = 231) Observation until progression (n = 115) *Paclitaxel 175 mg/m2 on Day 1 and gemcitabine 1250 mg/m2 on Days, 1, 8 q3w Primary endpoint: PFS from randomization Secondary endpoints: OS, toxicity, QOL, DOR Im Y-H, et al. ASCO 2012. Abstract 1003.
- 12. Maintenance vs Observationin MBC With Response to First-line Pac/Gem: Results Maintenance Observation HR (95% CI) P Value (n = 116) (n = 115) Median PFS, mos 7.5 3.8 0.73 (0.55-0.96) .026 Median OS, mos 36.8 28.0 0.65 (0.42-0.99) .048 Dose delivery, % Paclitaxel 94.7 95.9 Gemcitabine 86.6 91.7 Im Y-H, et al. ASCO 2012. Abstract 1003. Used with permission.
- 13. Maint vs Obsin MBC With Response to First-line Pac/Gem: Grade ≥ 3 AEs Cycles 1-6 Cycle 7 and Beyond Grade 3/4 AE, n (%) Maint Obs Maint Obs P Value P Value (n = 116) (n = 115) (n = 116) (n = 115) Neutropenia 80 (69.0) 78 (67.8) .57 71 (61.2) 1 (0.9) < .0001 Thrombocytopenia 0 1 (0.9) .50 1 (0.9) 0 .50 Anemia 3 (2.6) 6 (5.2) .33 1 (0.9) 0 .50 Azotemia 0 0 NS 5 (4.3) 0 .06 AST ↑ 0 0 NS 1 (0.9) 1 (0.9) .10 ALT ↑ 4 (3.4) 2 (1.7) .68 0 0 NS Febrile neutropenia 0 3 (2.6) .12 0 0 NS Diarrhea 0 2 (1.7) .25 1 (0.9) 1 (0.9) .10 Grade 3 neuropathy 4 (3.4) 1 (1.7) .68 4 (3.4) 2 (1.7) .68 Grade 2/3 neuropathy 32 (27.6) 39 (33.9) .30 49 (42.2) 18 (15.7) < .0001 Im Y-H, et al. ASCO 2012. Abstract 1003. Used with permission.
- 14. Maint vs Obsin MBC With Response to First-line Pac/Gem: Expert Perspectives Maintenance paclitaxel/gemcitabine in responding patients with MBC substantially prolonged PFS vs observation – 3.8 vs 7.5 mos (HR: 0.73; 95% CI: 0.55-0.96; P = .026) OS significantly prolonged in maintenance arm Maintenance therapy was tolerable and feasible No negative effect on QoL with maintenance Maintenance paclitaxel/gemcitabine after 6 cycles should be considered for selected patients – Hormone receptor negative – 50 yrs of age or younger – Visceral disease – Premenopausal – High tumor burden Im Y-H, et al. ASCO 2012. Abstract 1003.
- 15. Tratamento da DoençaMetastática QT Doença Metastática Paclitaxel vs Nab-Paclitaxel vs Ixabepilona Manutenção (?) Hormonioterapia Faslodex na primeira linha Everolimus Duplo bloqueio hormonal (?)
- 16. ⌫ “Virgem” de Tratamento ⌫ Tamoxifen sensível (TAM sens.) ⌫ Tamoxifen resistente (TAM resist.) ⌫ IA resistente (IA resist.)
- 18. Tamoxifeno (TAM) Inibidor daAromatase (IA) Fulvestranto (Fulv)
- 20. 80 70 60 50 45.6 40 32.6 32.9 32 31.2 30 21.1 21 20 17 10 ANAST ANAST LETRO EXEMEST TAM IA
- 21. 80 70 66.2 59.1 60 55.5 56.2 50 50 45.6 41.7 40 38 30 20 10 ANAST ANAST LETRO EXEMEST TAM IA
- 22. 12 11.1 9.9 10 9.4 8.2 8.2 8 5.6 6 5.8 6 4 2 0 ANAST ANAST LETRO EXEMEST TAM IA
- 25. 80 70 62 60 54.3 50 40 31.6 33.9 30 20 10 RO BC TAM FULV
- 26. 12 10 8.3 8 6.8 6 4 2 0 TAP TAM FULV
- 27. ⌫ “Virgem” de Tratamento ⌫ Tamoxifen sensível (TAM sens.) ⌫ Tamoxifen resistente (TAM resist.) ⌫ IA resistente (IA resist.)
- 29. Inibidor da Aromatase(IA) Fulvestranto (Fulv)
- 31.
- 32.
- 38. RR CB TTP* DOCB OS (%) (%) (m) (m) (m) FULVESTRANT 250 mg 9.1% 39.6% 5.5 16.6 22.8 500 mg 10.2% 45.6% 6.5 13.9 22,8 *HR=0.80; p=0.006
- 40. RR CB (%) TTP (%) (m) FULVESTRANT 14% 41.2% 23,4 ANASTROZOLE 8.8% 42% 13.1
- 43.
- 45. 70 60 50 40 32.2 31.5 30 20 10 6.7 7.4 0 RO BC EXEMEST FULV
- 46. Exemestane & Fulvestrant 3,7 months
- 47. IGF-1R, EGFR ER RAS PI3K E ER AKT RAF TSC2 TSC1 MEK mTOR ERK E ER Cell Proliferation
- 48. Everolimus 10 mgPO daily PFS Exemestane 25 mg PO daily Postmenopausal (N=485) ER+, Her2- OS , unresectable locally ORR advanced or metastatic R Bone Markers breast cancer refractory Placebo PO daily Safety to letrozole or Exemestane 25 mg PO daily PK anastrozole N = 724 (N=239) 2:1 (everolimus:placebo) Stratification: 1. Sensitivity to prior hormonal therapy 2. Presence of visceral disease No cross-over
- 49. BOLERO2 study RR CB (%) TTP (%) (m) EXEMESTANE 0,4% - 4.1 EXE + Everolimus 9.0% - 10,6
- 50. HR = 0.36(95% CI: 0.27–0.47) 100 Log rank P value = 3.3 x 10 -15 Probability of Event (%) 80 EVE + EXE: 10.6 Months PBO + EXE: 4.1 Months 60 40 20 Everolimus + Exemestane (E/N=114/485) Placebo + Exemestane (E/N=104/239) 0 0 6 12 18 24 30 36 42 48 54 60 66 72 78 Time (weeks)
- 51. 40 Everolimus + Exemestane 35 33,4% Placebo + Exemestane 30 P < 0.0001 25 20 18,0% P < 0.0001 15 9,5% 10 5 0,4% 0 Response Clinical Benefit
- 52. BOLERO2 10 AI resist. FULV EXEM 4 TAM resist. FULV 5 5 IA 5 500 mg FULV 23,4 Naive/ IA TAM sens. 10 TAM 6 0 5 10 15 20 25
Editor's Notes
- #5 CALGB, Cancer and Leukemia Group B; HR, hazard ratio; MBC, metastatic breast cancer; Nab-Pac, nab-paclitaxel; ODAC, Oncology Drugs Advisory Committee; Pac, paclitaxel; SD, stable disease.For more information on this study, go to: http://www.clinicaloptions.com/Oncology/Conference%20Coverage/Clin%20Onc%20June%202012/Tracks/Breast%20Cancer/Capsules/CRA1002.aspx
- #6 MBC, metastatic breast cancer; Nab-Pac, nab-paclitaxel; PFS, progression-free survival.For more information on this study, go to: http://www.clinicaloptions.com/Oncology/Conference%20Coverage/Clin%20Onc%20June%202012/Tracks/Breast%20Cancer/Capsules/CRA1002.aspx
- #7 CI, confidence interval; HR, hazard ratio; MBC, metastatic breast cancer; nab, nab-paclitaxel; OS, overall survival; pac, paclitaxel; PFS, progression-free survival.For more information on this study, go to: http://www.clinicaloptions.com/Oncology/Conference%20Coverage/Clin%20Onc%20June%202012/Tracks/Breast%20Cancer/Capsules/CRA1002.aspx
- #8 MBC, metastatic breast cancer.
- #9 AE, adverse event; MBC, metastatic breast cancer.For more information on this study, go to: http://www.clinicaloptions.com/Oncology/Conference%20Coverage/Clin%20Onc%20June%202012/Tracks/Breast%20Cancer/Capsules/CRA1002.aspx
- #10 MBC, metastatic breast cancer. For more information on this study, go to: http://www.clinicaloptions.com/Oncology/Conference%20Coverage/Clin%20Onc%20June%202012/Tracks/Breast%20Cancer/Capsules/CRA1002.aspx
- #12 CR, complete response; DOR, duration of response; HR, hormone receptor; MBC, metastatic breast cancer; OS overall survival; Pac/Gem, paclitaxel and gemcitabine; PR, partial response; QOL, quality of life; q3w, every 3 weeks; SD, stable disease.
- #14 AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Maint, maintenance; MBC, metastatic breast cancer; Obs, observation.
- #15 CI, confidence interval; HR, hazard ratio; Maint, maintenance; MBC, metastatic breast cancer; Obs, observation; Pac/Gem, paclitaxel, gemcitabine; PFS, progression-free survival; QoL, quality of life.