St. Gallen ASCO 2013 Carlos H. Barrios, MD PUCRS School of Medicine LACOG, LA Cooperative Group Instituto do Câncer, Hospital Mãe de Deus Porto Alegre, Brazil
%Disease Free Survival 100% 50% Breast Cancer Adjuvant Chemotherapy: Treatment Evolution 84% 67% 62% Trastuz DD TAC Antra CMF Surgery 35% 32% 26% 0% Bonadonna. NEJM, 2006. EBCTCG, Lancet, 2011. Bonilla, JNCI, 2010. 1 3 5 7 9 11 13 15 years Martin, ASCO 2010. Slamon, NEJM 2011
Quimioterapia Na sua opinião, para uma paciente Luminal A que você considera candidata à Quimioterapia, regimes menos intensivos como ACx4, CMFx6 ou TCx4 são adequados? 1.SIM 2.NÃO 3.ABSTENÇÃO
Quimioterapia Se você for indicar Quimioterapia (numa paciente Luminal A) vai escolher um regime que contenha uma antraciclina (em vez de CMF)? 1.SIM 2.NÃO 3.ABSTENÇÃO
Quimioterapia Se você for indicar Quimioterapia (numa paciente Luminal A) o regime deve conter um taxano? 1.SIM 2.NÃO 3.ABSTENÇÃO
Quimioterapia Se você for indicar Quimioterapia (numa paciente Luminal A) o regime deve ser prolongado para 6 ciclos? 1.SIM 2.NÃO 3.ABSTENÇÃO
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CALGB 40101:Rational AChas been the basic regimen for Adjuvant Rx Taxanes role in good prognosis pts is uncertain Single agent Taxanes could be as good as AC The ideal duration of Adjuvant therapy for good prognosis patients is unknown Presented By Lawrence N. Shulman, MD at 2013 ASCO Annual Meeting
Presented By Lawrence N. Shulman, MD at 2013 ASCO Annual Meeting [TITLE]
Presented By Lawrence N. Shulman, MD at 2013 ASCO Annual Meeting [TITLE]
Presented By Lawrence N. Shulman, MD at 2013 ASCO Annual Meeting [TITLE]
[TITLE] 1. Equivalence of single agent T vs. AC (Upper boundary 95% CI HR <1.30) 2. Superiority of 6 cycles vs. 4 cycles Primary Endpoint: DFS Presented By Lawrence N. Shulman, MD at 2013 ASCO Annual Meeting
CALGB 40101:Patient Characteristics 3871 patients (target 567 RFS events in 4646 patients) Median Age: 53 years (24-84) 90% pn0 68% RH+ HER2 52%unknown Of those tested, 84% negative 2002: 570 patients enrolled Paclitaxel 80mg/m2 weekly (12-18 weeks) AC (60/600mg/m2) q3 weeks 2003: Both schedules revised Paclitaxel 175mg/m2 q2 weeks AC (60/600mg/m2) q2 weeks 2008: Both 6 cycle arms were dropped due to slow accrual Presented By Lawrence N. Shulman, MD at 2013 ASCO Annual Meeting
CALGB 40101:DFS/OS Results Median Follow up 6.1 years DFS 437 events HR = 1,26 (favors AC) (IC95% 1,05-1,53); p=0.02 OS 266deaths HR = 1,27 (favors AC) (IC95% 1,00-1,62); p=0,05 Presented By Lawrence N. Shulman, MD at 2013 ASCO Annual Meeting
Presented By Lawrence N. Shulman, MD at 2013 ASCO Annual Meeting
CALGB 40101:Conclusions In this group of women with EBC and good prognosis 90% PLN negative, 68% HR positive, 84% HER2 negative (probably) There was no equivalence of T to AC ACwas more toxic: all treatment related deaths (N=9) were in the AC arm In this population: AC 4 = AC 6 Presented By Lawrence N. Shulman, MD at 2013 ASCO Annual Meeting
EBCTCG -2012 Individual-patient-data meta-analyses of randomized trials comparing: Any T + A based regimen versus the same, or more, non-t chemotherapy (n=44,000); One A based regimen versus another (n=7000) One A based regimen versus CMF (n=18,000); Polychemotherapy versus no chemotherapy (n=32,000). EBCTCG, Peto R, et al. Lancet. 2012 Feb 4;379(9814):432-44. Epub 2011 Dec 5.
Chemotherapy: EBCTCG - 2012 EBCTCG, Peto R, et al. Lancet. 2012 Feb 4;379(9814):432-44. Epub 2011 Dec 5.
EBCTCG -2012 What Chemotherapy? Standard 4AC and standard CMF were equivalent (RR 0 98, SE 0 05, 2p=0 67), but A-based regimens with substantially higher cumulative dosage than standard 4AC (e.g., CAF or CEF) were superior to standard CMF (RR 0 78, SE 0 06, 2p=0 0004). Trials versus no chemotherapysuggested greater mortality reductions with CAF (RR 0 64, SE 0 09, 2p<0 0001) than with standard 4AC (RR 0 78, SE 0 09, 2p=0 01) or standard CMF (RR 0 76, SE 0 05, 2p<0 0001). EBCTCG, Peto R, et al. Lancet. 2012 Feb 4;379(9814):432-44. Epub 2011 Dec 5.
EBCTCG -2012 Extending treatment duration: Addition of 4 separate cycles oft to a fixeda based control regimen, reduced BC mortality(rr 0 86, SE 0 04, two-sided significance [2p]=0 0005). Counterbalancing those 4 extra T cycles with extra cycles of other cytotoxic drugs in the controls (roughly doubling non-t dosage), there was no significant difference (RR 0 94, SE 0 06, 2p=0 33). EBCTCG, Peto R, et al. Lancet. 2012 Feb 4;379(9814):432-44. Epub 2011 Dec 5.
Chemotherapy: EBCTCG - 2012 EBCTCG, Peto R, et al. Lancet. 2012 Feb 4;379(9814):432-44. Epub 2011 Dec 5.
EBCTCG -2012 In all analyses involving T-based or A-based regimens, proportional risk reductions were little affected by age (up to 70), nodal status,tumor diameter or differentiation (moderate or poor; few were well differentiated), estrogen receptor status, or tamoxifen use. Hence,T+A based (or higher cumulative dose A-based) reduced breast cancer mortality by, on average, about30%. 10-year overall mortality differences paralleled breast cancer mortality differences, despite taxane, anthracycline, and other toxicities. Low absolute risk implies low absolute benefit, but information was lacking abouttumor gene expression markers or quantitative IHC that might help to predict risk. EBCTCG, Peto R, et al. Lancet. 2012 Feb 4;379(9814):432-44. Epub 2011 Dec 5.
Quimioterapia Numa paciente com doença subtipo basal (Triplo Negativa), a quimioterapia deve conter uma platina. 1.SIM 2.NÃO 3.ABSTENÇÃO
[TITLE] Presented By Gunter Von Minckwitz, MD at 2013 ASCO Annual Meeting
[TITLE] Presented By Gunter Von Minckwitz, MD at 2013 ASCO Annual Meeting
[TITLE] Presented By Gunter Von Minckwitz, MD at 2013 ASCO Annual Meeting
GeparSixto: Objectives Primary Endpoint: pcr rates (ypt0ypn0)pm vs. PMCb Secondary Endpoints: Compliance and toxicity Efficacy with other pcr definitions Efficacy in TNBC and HER2 positive tumors Clinical CR Breast Preservation Rate Presented By Gunter Von Minckwitz, MD at 2013 ASCO Annual Meeting
[TITLE] Presented By Gunter Von Minckwitz, MD at 2013 ASCO Annual Meeting
[TITLE] Presented By Gunter Von Minckwitz, MD at 2013 ASCO Annual Meeting
GeparSixto: Conclusions Significant increase in pcr rates: 37,2% to 46,7% with the addition of Carboplatin Absolute increase of 20% in the TN population, no difference in the HER2 positive patients Increased efficacy in spite of high rate of discontinuations (39% for PM and 48% for PMCb) Presented By Gunter Von Minckwitz, MD at 2013 ASCO Annual Meeting
St. Gallen ASCO 2013 Carlos H. Barrios, MD PUCRS School of Medicine LACOG, LA Cooperative Group Instituto do Câncer, Hospital Mãe de Deus Porto Alegre, Brazil