Download the ESMO 2012 Abstract Book - Oxford Journals

90 mg/m2-cyclophophamide 600 mg/m2 d1 for 3 cycles, followed by a second
sequence with paclitaxel (P) 150 mg/m2- gemcitabine (G) 2500 mg/m2 d1 +/trastuzumab
2mg/kg/wk according to status Her2 (n= 73). In study A pts did not
receive trastuzumab regardless of Her2 status. Ki67 was centrally assessed by IHC
(Master Diagnostica clon SP6). Tumors were considered to have high proliferation
rates (Ki67) if ≥ 20% of cell nuclei stained positive. Median age was 48 years. Her2+
was observed in 31%, HR negative 34%, grade III 46% and high Ki67 47%.
Pathological complete response (pCR) defined as absence of invasive cells in breast
and lymph node was achieved in 35 pts (28%). Univariate and multivariate logistic
regression models were used to study the association of each clinical-pathological
variable with pCR.
Results: High Ki67 was the main predictive factor of pCR to NC. In the univariate
analysis histological grade (p = 0.001), HR (p < 0.001), Ki67 (p = 0.001) and p53 (p
< 0.001) were statistically associated with pCR. A multivariate logistic regression
showed than only high Ki67 (p = 0.02; OR = 5.5 CI95% 1.2- 18) and HR (p = 0.045;
OR = 0.25 CI95% 0.05-0.97) were predictive for pCR.
Conclusion: High proliferation determined by ki67 marker is an independent
predictive factor for pCR in locally advanced breast cancer patients treated in two
dose-dense NC schedules.
Disclosure: All authors have declared no conflicts of interest.
269P NEOADJUVANT CHEMOTHERAPY IN OPERABLE BREAST
CANCER: DATA FROM THE ASTER STUDY (AT FOR 3 CYCLES
FOLLOWED BY CMF FOR 3 CYCLES)
E. Puma1 , P. Mariani1 , S. Damian1 , M.C. Dazzani1 , E. De Benedictis1 , M. Parati2 ,
L. Sica2 , A. Tessari1 , F.G.M. De Braud1 , A. Moliterni1 1
Medical Oncology, Istituto Nazionale dei Tumori di Milano, Milan, ITALY,
2
Oncologia Medica, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milano,
ITALY
Background: The ECTO-1 study demonstrated the efficacy of concurrent
doxorubicin and paclitaxel (AT) for 4 cycles followed by cyclophosphamyde/
methotrexate/fluorouracil (CMF) for 4 cycles in the neoadjuvant treatment of
operable breast cancer (Gianni L. et al. Clin Cancer Res 2005). With the purpose of
ameliorating the tolerability of the regimen, we designed the ASTER study to reduce
both the duration and the total dose of neo-/adjuvant treatment with AT followed by
CMF. Herein we report on the efficacy of the neoadjuvant portion of the trial.
Methods: A total of 70 patients with operable breast cancer were enrolled between
September 2008 and November 2011. Median age was 51 years (range 32-73); 74% of
patients presented with hormone receptor positive (HR +) and 26% of patients with
hormone receptor negative (HR -); 8% of patients presented HER2 overexpression/
amplification; most of the patients had cT2 (96%); half presented with node
involvement cN1 (54%). Patients were treated with neoadjuvant Adriamycin (60 mg/
mq) + Paclitaxel (200 mg/mq) q21 for 3 cycles followed by CMF i.v. 1, 8q28 for 3
cycles.
Results: The pathological complete response (pCR), defined as the absence of
neoplastic cells in the primary tumor was obtained in 11.5% of cases; tnpCR, defined
as the absence of neoplastic cells in the primary tumor and in nodes, was obtained in
10% of cases. Overall, 29% of patients with triple negative breast cancer achieved a
pCR, while only 6% of HR positive breast cancer achieved a pCR.
Conclusions: Neoadjuvant treatment with three cycles of AT followed by three cycles
of CMF is effective in patients with operable breast cancer. The rate of pCR matched
perfectly with the data obtained with the original schema AT x 4 followed by CMF x
4 in 69 patients treated with primary chemotherapy at our institute, within the
ECTO-1 study. The ASTER study sets the base for developing a less toxic
chemotherapy regimen sequential and non-cross resistant containing anthracycline
and taxane for the treatment of operable breast cancer.
Disclosure: All authors have declared no conflicts of interest.
270P LONG-TERM OVERALL SURVIVAL (OS) AND DISEASE-FREE
SURVIVAL (DFS) ACCORDING TO PCR IN BREAST CANCERS
SUBTYPES: LUMINAL A AND B, TRIPLE NEGATIVE AND
HER2 + , TREATED BY NEAODJUVANT CHEMOTHERAPY
(NCT)
C. Abrial 1 , Q. Wang-Lopez 1 , M. Mouret-Reynier 2 , P. Dubray-Longeras 2 , I. van
Praagh-Doreau 2 , X. Durando 2 , P. Gimbergues 3 , J. Nabholtz 2 , F. Penault-Llorca 4 ,
P. Chollet 2
1 Clinical Research, Centre Jean Perrin, Clermont-Ferrand, FRANCE, 2 Oncology
Department, Centre Jean Perrin, Clermont-Ferrand, FRANCE, 3 Surgery
Department, Centre Jean Perrin, Clermont-Ferrand, FRANCE, 4 Dept. de
Pathologie, Centre Jean Perrin, Clermont-Ferrand Cedex, FRANCE
Background: In breast cancer, positive Hormone Receptors (HR) constitute a
favourable prognostic factor whereas HER-2 overexpression is an adverse prognostic
factor associated with a more aggressive tumor. In a retrospective database of 282
Annals of Oncology
breast cancer patients diagnosed from 1991 to 2006, we analysed the overall survival
(OS) and the disease-free survival (DFS) of 4 phenotypes: HR-/HER-2- (triple
negative, TN); HR + /Ki-67 < 20% (luminal A), HR + /Ki-67 > 20% or Her2+ (luminal
B) and HER-2 overexpression (HER-2 + /HR-).
Patients and methods: Median diameter of the invasive tumour was 40 mm
[10-130]. 231 (82%) patients had a canalar carcinoma. 33% of the tumours were
grade III SBR. Patients received either an anthracycline-based chemotherapy (47%), a
taxane-based chemotherapy (21%) or a combination of both (32%). The median
number of NCT courses was 6 [1-8] followed by a surgery for 97.6%, a radiotherapy
for 93%, an adjuvant chemotherapy for 20% and/or an hormonotherapy for 56%.
Only 5 patients received adjuvant herceptin for 1 year. In the different subgroups, we
had 123 luminal A tumors (44%), 67 luminal B tumours (24%), 21 Her2+ tumours
(7%) and 71 TN tumours (25% of patients).
Results: According to tumour’s phenotype, the pCR (Chevallier’s classes1+2)
was: 3.3% for luminal A, 16.6%, for luminal B, 33.3% for Her2+ HR- and 26%
for triple negative tumours. On 2 April 2012, the median follow-up was 148
months (range, 63- 252). We evaluated the OS and the DFS in the four
subgroups, at 10 years. -For TN: OS and DFS were 58.5% and 56.2%. -For
luminal A: OS and DFS were 76.1% and 64.7%. -For luminal B: OS and DFS
were 81.7% and 72.4%. -For Her2 + HR- subgroup: OS and DFS were 64.5% and
56.4%. pCR is an objective method improvement after NCT, but it is variable
among subsets, and may constitute an acquired prognostic factor. However, it
was much smaller in hormonal-positive tumors subsets and may there not be an
endpoint per se. We observed a significant improvement of DFS and OS for
patients who reached a pCR only in TN breast cancer. However Her2 subset
may be too small to reach significance here.
Conclusion: OS and DFS were better in luminal A and B subgroups. Conversely OS
and DFS decreased for TN and Her2+ subtypes. When TN breast cancer patients
reached a pCR, OS and DFS were significantly improved.
Disclosure: All authors have declared no conflicts of interest.
271P ADDITIONAL SAFETY RESULTS OF HANNAH: A PHASE III
RANDOMISED, OPEN-LABEL, INTERNATIONAL STUDY OF
THE SUBCUTANEOUS FORMULATION OF TRASTUZUMAB (H)
IN HER2-POSITIVE EARLY BREAST CANCER PATIENTS
C. Jackisch 1 , M. Dank 2 , G. Frasci 3 , K.H. Park 4 , R.I. Lopez 5 , M. Johnston 6 ,
D. Heinzmann 7 , H. Weber 7 , G. Ismael 8
1 Department of Obstrics and Gynecology, Klinikum Offenbach GmbH,
Offenbach, GERMANY, 2 Semmelweis Egyetem, Radiológiai és Onkoterápiás
Klinika, Budapest, HUNGARY, 3 Division of Medical Oncology A, National Tumor
Institute, Naples, ITALY, 4 Department of Internal Medicine, Korea University
Anam Hospital, Seoul, KOREA, 5 Medical Oncology Department, National
Oncology Institute, Panama, PANAMA, 6 Genentech Inc, South San Francisco,
CA, UNITED STATES OF AMERICA, 7 Clinical Science, F. Hoffmann-La Roche
Ltd, Basel, SWITZERLAND, 8 Medical Oncology, Fundation Amaral
CarvalhoHospital of Jau, Jau, BRAZIL
Background: HannaH demonstrated non-inferiority of the fixed-dose subcutaneous
(SC) formulation of H compared with the intravenous (IV) formulation, based on
co-primary endpoints of pharmacokinetics (C trough) and efficacy (pCR) (Jackisch
et al, EBCC 2012).
Methods: Pts with HER2-positive, operable, locally advanced or inflammatory BC
were randomised to receive 8 cycles of chemotherapy (4x docetaxel 75 mg/m 2
followed by 4x FEC 600/75/600 mg/m 2 ) concurrently with 3-wkly H, either SC (600
mg/5 mL) or IV (8 mg/kg to 6 mg/kg). After surgery, pts continued H-SC or IV to
complete 1 year of treatment. Safety has been monitored until 24 mths after last dose
of H, including cardiac monitoring.
Results: Safety data from 298 (IV) /297 (SC) HannaH pts were analysed. At a
median F/U of 12.3 months, 116 pts had completed adjuvant treatment and
received a median of 17.5 (IV) and 17.0 (SC) H cycles. Pt characteristics were
balanced at baseline. Overall, safety was comparable between arms. Most
common AEs (>25% in either arm) were alopecia, nausea, neutropenia,
diarrhoea, asthenia, and fatigue, with similar incidence in the two arms.
Incidence of severe AEs (≥ grade 3) was comparable between arms (both 52%);
the most common of which were haematologic (36.9 [IV] v 35.4% [SC]), GI (6.4
v 5.7%) and infections (5.0 v 6.7%). Serious AEs (SAEs) were reported in 12.4%
(IV) v 20.9% (SC) of pts. The imbalance was largely driven by increased
reporting of SAEs in the “infections” disease category in the SC v the IV arm
(38.7 v 35.1%). Multiple logistic regression analyses did not reveal interactions
between route of H treatment, body weight, and exposure (AUC) for SAEs or
grade 3–5 AEs. AEs led to the withdrawal of 2.3% (IV) and 5.7% (SC) pts, with
a contribution from cardiac AEs (3.0% [SC] v 1.3% [(IV]). Grade 1/2 AEs were
reasons for withdrawal in 43% (IV) v 61% (SC) of pts. Grade 1/2 cardiac AEs
led to withdrawal in 1.0% (IV) v 2.0% (SC) of pts. Incidence of cardiac AEs was
similar in both arms: 12.1% % (IV) v 11.4% (SC).
Conclusions: The safety profile of H-SC was comparable to that of H-IV.
Detailed analyses of observed imbalances in SAEs and withdrawals will be
provided.
ix102 | Abstracts Volume 23 | Supplement 9 | September 2012