Presentation on theme: "516 (32723) Phase III trial comparing AC (x4)taxane (x4) with taxane (x8) as adjuvant therapy for node-positive breast cancer: Results of N-SAS-BC02."— Presentation transcript:
1 516 (32723) Phase III trial comparing AC (x4)taxane (x4) with taxane (x8) as adjuvant therapy for node-positive breast cancer: Results of N-SAS-BC02 trial (Japan)T. Watanabe, M. Kuranami, K. Inoue, N. Masuda, K. Aogi, H. Iwata, H. Mukai, S. Tanaka, T. Yamaguchi, Y. Ohashi
2 BackgroundDoxorubicin and cyclophosphamide (AC) x 4 paclitaxel x 4 is a standard regimen for postoperative chemotherapy.Rare but serious side effects (e.g., cardiac failure, secondary leukemia) are major concerns with AC.AC cannot be used in some patients.Relative efficacy of docetaxel to that of paclitaxel needs to be clarified.
3 Trial Design ACP R A N D O M I Z E ACD PTX DTX 3 6 9 12 15 18 21 weeks ADM 60 mg/m2CPA 600 mg/m2RANDOMIZEACDPaclitaxel 175 mg/m2PTXDocetaxel 75 mg/m2DTXPts with BCS received RT.Pts with ER(+) BC received TAM or an AI for 5 yrs.36912151821weeks
4 Primary objectivesTo compare disease-free survival (DFS) with AC (x4)taxane (x4) vs. taxane (x8)To compare DFS with paclitaxel (x8) vs. docetaxel (x8) in node-positive breast cancer
5 Exploratory analysesTo find subsets of patients who benefit from additional treatment with ACSubsets:HER2 positive vs. HER2 negative or unknownER positive vs. ER negative or unknown
6 Inclusion Criteria Stage I to IIIA invasive breast cancer Histologically involved axillary lymph nodesAge yearsPS (ECOG) 0, 1No prior chemotherapy or endocrine therapyAdequate organ functionsWritten informed consent
7 Statistical Considerations Hypothesis 1: A taxane (x8) is not inferior to AC (x4) a taxane (x4) Hypothesis 2: One of the taxanes is superior or equivalent to the other. Planned N = 1200 (based on planned events (≥320) in hypothesis 1) a=0.05; 1-sided (non-inferiority); power (1-b) = 0.80
8 Patient accrualBetween December 2001 and April 2006, 1060 patients were randomized at 84 institutions in Japan.Date of first analysis: June 15, 2008
9 Patient Disposition ACP 263 ACD 265 PTX 267 DTX ACP 263 ACD 265 PTX Patients randomly assigned (n=1060)ACP263ACD265PTX267DTXPatients eligible for this trial (n=1060)ACP263ACD265PTX267DTXDid not receive protocol therapy (n=16)ACP3ACDPTX4DTX6Patients analyzed for safety and efficacy (n=1044)ACP260ACD262PTX263DTX259Did not complete protocol therapy (n=142)ACP33ACD36PTX35DTX38Patients completed protocol therapy (n=902)ACP227ACD226PTX228DTX221
14 Disease-free Survival 10090Percent probability8070：ACP：ACD：PTX：DTX6050～1234Time from randomization （years）
15 Disease-free Survival Summary of events (disease-free survival)ACPACDPTXDTXNo. of pts258255261257Hypothesis 1:A taxane alone is not inferior to AC + a taxaneHazard ratio(AC + a taxane as standard)1.2699% CI90% CIp value0.67Hypothesis 2: Whether PTX or DTX is more effective(PTX as standard)0.8199.5% CI95% CI0.08・Two confidence intervals are calculated for each endpoint, taking into accountmultiplicity due to interim analysis.・Final analysis will be planned number of events (>=320) are observed.
16 Disease-free Survival 1001009090Percent probability808070706060： AC –>Taxane： Taxane：ACD+DTX：ACP+PTX5050～Hazard ratio (99%CI)：1.26(0.92 – 1.72)Hazard ratio (99.5%CI)：0.81(0.57 – 1.14)～12341234Time from randomization （years）Time from randomization （years）
17 AC Taxane vs. Taxane Subset according to HER2 HER2 positiveHER2 negative/unknown1001009090Percent probability808070706060： AC Taxane： Taxane50： AC Taxane： Taxane50～Hazard ratio (95% CI): 1.63(1.05 – 2.54)～Hazard ratio (95% CI): 1.13(0.85 – 1.50)12341234Time from randomization（years）Time from randomization （years）・Interactions between the response to AC and HER-2 positive/HER-2negative/unknown status, P=0.17
18 AC Taxane vs. Taxane Subset according to ER ER positiveER negative1001009090Percent probability808070706060：AC Taxane：Taxane：AC Taxane：Taxane5050Hazard ratio (95%CI)：1.32(0.90 – 1.95)～Hazard ratio (95%CI)：1.22(0.90 – 1.66)～12341234Time from randomization （years）Time from randomization （years）
19 Summary (1)Taxane (x8) is not demonstrated to be non-inferior to AC (x4) a taxane (x4) in the study group as a whole in terms of DFS.Docetaxel (75 mg/m2) is superior to paclitaxel (175 mg/m2) when given every 3 weeks in terms of DFS.In the subset of HER2-positive patients, AC (x4) a taxane (x4) produced superior DFS than did a taxane (x8). This result was not obtained in patients with HER2-negative or unknown tumors.For ER, there was no interaction with the addition of AC.
20 Summary (2) Regarding the incidences of adverse events: Nausea and vomiting were higher with AC (x4) a taxane (x4) than with taxane (x8) .Edema and febrile neutropenia were higher with docetaxel (75 mg/m2) than with paclitaxel (175 mg/m2) .Sensory neuropathy was higher with paclitaxel (175 mg/m2) than with docetaxel (75 mg/m2) .
21 ConclusionsAC can be omitted in certain subsets of patients with postoperative breast cancer.When given every 3 weeks, docetaxel (75 mg/m2) improves DFS in women with node-positive breast cancer as compared with paclitaxel (175 mg/m2) .The expression of HER2 may be associated with a benefit from the addition of AC.