Bcirg 006 - final abstract sabcs.doc

Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by
docetaxel (AC→T) with doxorubicin and cyclophosphamide followed by docetaxel and
trastuzumab (AC→TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2
positive early breast cancer patients: BCIRG 006 study

Slamon D1, Eiermann W 2, Robert N, Pienkowski T, Martin M, Pawlicki M, Chan A, Smylie
M3, Liu M, Falkson C, Pinter T, Fornander T, Shiftan T, Valero V, Von Minckwitz G2,
Mackey J3, Tabah-Fisch I, Buyse M, Lindsay MA4, Riva A4, Bee V4, Pegram M 1, Press M,
Crown J, on behalf of the BCIRG 006 Investigators.
UCLA, Los Angeles, CA1; GBG, Munchen, Frankfurt, Germany2; US Oncology, Houston,
TX; Maria Sklodowska-Curie (MSC) Centre, Warsaw, Poland; GEICAM, Madrid, Spain;
MSC Institute, Krakow, Poland; Mount Hospital, Perth Australia; Cross Cancer Institute,
Edmonton, Canada3; Sun Yat -Sen Cancer Center, Taipei, Taiwan; University of Alabama,
Birmingham, AL; Petz Aladar Korhaz, Gyor, Hungary; Karolinska University Hospital,
Stockholm, Sweden; Sharp Healthcare, San Diego, CA; MDACC Houston, TX; Sanofi-
Aventis, Paris, France; IDDI, Brussels, Belgium; CIRG, Paris, France4; USC, LA, CA;
ICORG, Dublin, Ireland.
Background: This study evaluates the benefit of two trastuzumab-based (H) regimens in
HER2 amplified breast cancer with the intent of integrating H to maximize efficacy and
minimize known cardiotoxicity.
Material and Methods: HER2 amplified (centralized FISH) patients with axillary lymph
node (LN) positive or high risk LN negative were randomized to either AC (60/600 mg/m2
q3wk x4) followed by T (100 mg/m2 q3wk x 4) or two H-containing regimens; AC followed
by T with H x 1 year (q1wk during chemo/q3wk during FUP) or TCarbo (75 mg/m2 / AUC6
q3wk x 6) with H x 1 year. Patients were prospectively stratified by positive LN (0, 1-3 vs
4+) and hormone receptor (HR) status. Patients with HR+ tumors received hormonal therapy
for 5 yrs after chemotherapy. The primary endpoint was disease-free survival (DFS) with 80%
power (0.05 significance level) to detect an absolute difference of 7%. Secondary endpoints
included OS, safety, including cardiotoxicity (symptomatic events
ischemia/infarction, gr3/4 arrhythmia- and asymptomatic LVEF decline). We report the
results of the first planned, protocol-mandated interim analysis conducted after 322 events
(breast cancer relapse, second primary malignancy or death).
Results: A total of 3222 pts (1073 in AC-T, 1074 in AC-TH and 1075 in TCH) were
recruited between Apr 2001 and Mar 2004. At a median follow-up of 23 months, the two H-
containing arms have both met the DFS endpt: hazard ratio of 0.49 with AC-TH, p-
value=0.00000048 and 0.61 with TCH, p-value=0.00015 (as compared to AC-T). At this
time, there is no statistically significant difference btw the two H-containing arms perhaps due
to the small number of events currently separating them. Symptomatic cardiac events: AC-T:
1.2% vs AC-TH: 2.3%, p-value=0.046; AC-T vs TCH: 1.2%, p value=1.00. Absolute LVEF
decline >15% and below lower limit of normal occurred in 0.6% pts in AC-T, 2.4% in AC-
TH and 0.4% in TCH arms respectively (AC-T vs AC-TH (p=0.001); AC-T vs TCH (p=0.54).
Discussion: Result of this trial confirms the benefit of H when combined with docetaxel (AC-
TH) or with docetaxel and carboplatin (TCH) without an anthracycline. There are fewer
severe cardiac adverse events when H is administered without prior A. Longer follow-up is
needed in order to confirm whether non -A-based adjuvant H regimens will have efficacy
comparable to A-based regimens.

Source: http://www.bcirg.org/NR/rdonlyres/euynx4wi7wx6yq4qenuxw5ok6bbclmm5ckfz5vyo7kdkrbg5iq4ketb23g4epbwzpld5vhqbsiolga72y2itf7plpqb/BCIRG+006+-+Final+Abstract+SABCS.pdf