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Table: 198P
PFS OS
Median, mo HR Median, mo HR
Subgroup
VEGF-A
PL BV PL BV
≤ median 12.3 18.6 0.52 43.0 48.5 0.87
> median 11.0 17.5 0.70 33.9 41.8 0.78
≤ Q3 12.3 18.6 0.59 45.1 48.5 0.89
> Q3
VEGFR-2
9.7 13.8 0.67 28.6 37.7 0.72
≤ median 12.0 18.0 0.68 35.1 40.6 0.90
> median 10.4 18.2 0.53 38.4 48.5 0.69
≤ Q3 11.0 17.3 0.63 38.2 41.8 0.87
> Q3 12.5 22.1 0.46 38.6 − 0.59
Q = quartile
continued alone until progression or for up to 15 mo. GOG-0218 includes extensive
BM evaluation to identify pts benefitting most from BV. Analysis of plasma VEGF-A
and VEGFR-2 was prioritised based on encouraging findings in BV trials in several
tumour types.
Methods: Pts with newly diagnosed stage IV or macroscopic optimal stage III OC
were randomised to 6 cycles (c) of CT with: placebo (PL) c2−22 (arm A); BV c2
−6 → PL c7−22 (arm B); or BV c2−22 (arm C). Post-surgery pre-CT plasma
samples were analysed using a multiplex ELISA. Baseline (BL) BM levels were used
to dichotomise pts. Potential interactions between BM levels and PFS (1° endpoint)
and overall survival (OS; 2° endpoint) were tested using log-rank testing and Cox
regression approaches.
Results: Post-surgery samples were available from 582 of 1248 pts in arms A and
C. Median BL VEGF-A and VEGFR-2 levels were 144.3 pg/mL and 14.7 ng/mL,
respectively. No significant interaction was seen at α = 0.05. Exploratory analyses with
other cut-offs are hypothesis generating for potential predictive (VEGF-A and
VEGFR-2) or prognostic (VEGF-A: OS) value. Exploratory analyses revealed no
correlation between plasma VEGF-A and time since surgery.
Conclusions: The potential prognostic (VEGF-A) and predictive (VEGF-A,
VEGFR-2) value seen in breast, pancreatic and gastric cancers was not apparent in
post-surgery samples from GOG-0218 using a median cut-off. Results with other
cut-offs provide a rationale for further investigation of potential prognostic and
predictive value. Findings may reflect differing biology and interplay between
VEGF-A isoforms across tumour types. The possible impact of pre- vs post-surgery
samples is also being investigated.
Disclosure: R.A. Burger: RB has served on Advisory Boards for Roche/Genentech. R.
Mannel: RM has served on Advisory Boards for Genentech. V. Henschel: VH is
employed by and holds shares in Roche. M. Sovak: MS is an employee of Genentech.
S.J. Scherer: SS is an employee of Genentech Inc. S. De Haas: SdH is an empoloyee
of F Hoffmann-La Roche Ltd. C. Pallaud: CP is an employee of F Hoffmann-La
Roche Ltd. All other authors have declared no conflicts of interest.
199P CHANGE IN HER2 STATUS AFTER NEOADJUVANT
CHEMOTHERAPY AND THE SURVIVAL IMPACT
A. Yoshida 1 , N. Hayashi 1 , O. Sachiko 2 , Y. Kajiura 1 , H. Yagata 1 , S. Nakamura 3 ,
H. Yamauchi 1
1 Breast Surgical Oncology, St. Luke’s International Hospital, Tokyo, JAPAN,
2 Researcher, Center For Clinical Epidemiology St. Luke’s Life Science Institute,
St. Luke’s International Hospital, Tokyp, JAPAN, 3 Department of Breast Surgical
Oncology, Showa University School of Medicine, Tokyo, JAPAN
Background: The incidence of change in HER2 status in primary breast cancer after
neoadjuvant chemotherapy (NAC) and whether the change affect prognosis is not
well known.
Patients and methods: One hundred eighty-four patients who were treated with
anthracycline- and/or taxane-based NAC and had non-pathologic complete
response between 2003 and 2005 in our hospital were enrolled. Human
epidermal growth factor receptor 2 (HER2) status was assessed in specimen by
core needle biopsy before NAC and in residual tumor of surgical specimen. We
determine the impact of change in HER2 status on recurrence-free survival
(RFS). All patients had not received HER2-targeting agents during study period.
HER2-positive was defined as 3+ by immunohistochemistry and/or amplification
by fluorescent in situ hybridization. Association between clinicopathologic
factors, including clinical T stage, estrogen receptor (ER), progesterone receptor
(PR), Nuclear grade (NG), and clinical response, and change in HER2 status
after NAC were determined.
Result: A median follow-up term was 74.1 months (range, 6.0 to 120.9 months).
One hundred forty-nine of the 184 patients (80.9%) had HER2-negative tumors
Annals of Oncology
and 35 patients (19.0%) had HER2-positive tumor before NAC. HER2-negative
tumors in 5 of the 149 patients (3.3%) changed to HER2-positive tumor.
HER2-positive tumors in 7 of the 35 patients (20%) changed to HER2-negative
tumor. In terms of RFS, there was no difference between patients with and
without change in HER2 status in both of the 149 patients with HER2-negative
tumors and 35 patients with HER2-positive tumors before NAC (p = 0.56, p =
0.96, respectively). Any clinicopathologic factors were not associated with change
in HER2 status after NAC.
Conclusion: We herein reported the incidence of change in HER2 status after NAC
with the large sample size. However, change in HER2 status did not seems to affect
prognosis due to the small events in this study. Further well-powered study in
needed to confirm the prognostic impact of change in HER2 status and needs
of HER2-targeting agents for these populations.
Disclosure: All authors have declared no conflicts of interest.
200P NEW IMAGING AND MOLECULAR BIOMARKERS TO PREDICT
PATHOLOGICAL RESPONSE TO BEVACIZUMAB-BASED
TREATMENT IN NEOADJUVANT BREAST CANCER
J. Garcia-Foncillas 1 , A. Plazaola 2 , B. Hernando 3 , R. Sanchez 4 , I. Alvarez 5 ,
A. Antón 6 , P. Martinez Del Prado 7 , A. Llombart 8 , S. Sherer 9 , J.M. Lopez-Vega 10
1 Oncology, Hospital Universitario. Fundacion Jimenez Diaz. Universidad
Autónoma de Madrid, Madrid, SPAIN, 2 Oncology, Onkologikoa, Donosti, SPAIN,
3 Oncology, Hospital de Burgos, Burgos, SPAIN, 4 Oncology, Hospital San Pedro,
Logroño, SPAIN, 5 Medical Oncology Dept., Hospital Donostia, San Sebastian,
SPAIN, 6 Oncology, H U Miguel Servet, Zaragoza, SPAIN, 7 Medical Oncology,
University Hospital of Basurto, Bilbao, SPAIN, 8 Medical Oncology Service,
Hospital Arnau de Vilanova, Valencia, SPAIN, 9 Research, Roche A.G. Basel,
Basel, SWAZILAND, 10 Servicio de Oncologia Medica, Hospital Universitario
Marques de Valdecilla, Santander, SPAIN
Background: Early and robust prediction of pathological response in neoadjuvant
breast cancer may help to identify which patients may benefit from
bevacizumab-based therapy. Different imaging and molecular approaches have been
0evaluated in a multicenter clinical trial.
Methods: 73 chemotherapy naïve, stage II and III breast cancer (BC) patients
(pts) were enrolled in a phase II, single-arm, multicenter, open-label and
prospective clinical trial. Pts received single infusion of bevacizumab (15 mg/
kg)(C1)3weekspriortothebeginningof neoadjuvant chemotherapy (NAC)
consisting of 4 cycles of docetaxel (60 mg/mq), doxorubicin (50 mg/mq) and
bevacizumab (15 mg/ kg) every 21 days (C2-C5), followed by surgery. Tumor
proliferation, hypoxia and perfusion were evaluated respectively using
18F-Fluorothymidine (FLT) and 18F-Misonidazole (FMISO) positron emission
tomography (PET/CT) and dynamic contrast enhancement magnetic resonance
(DCE-MR). Serial imaging studies were performed in parallel at several time
points including baseline (BL) and 14-21 days after bevacizumab alone (C1).
Biomarker expression was assessed by immunohistochemistry (Ki67, CD31,
CD31/Ki67, VEGFR2, pVEGFR2 [Y951]) before and after bevacizumab
infusion (C1). Gene expression was analyzed using Affimetrix Human Gene
ST 1.0.
Results: Decrease in FMISO uptake >10% yielded a ROC curve area of 0.7 (95% CI:
0.56 - 0.85) with high specificity (94%). Decrease in the phosphorilation status of
VEGFR2 (Y951) >70% yielded a receiver operating characteristic (ROC) curve area of
0.681 (95% CI: 0.536 - 0.825) with 84% sensitivity and 95% specificity. The change
in phosphorilation status of VEGFR2p remains a significant predictor biomarker of
response in multivariate analysis (OR = 0.9, IC%95 0.96-0.99, p = 0.04) after adjusting
for clinical-pathological characteristics.
ix82 | Abstracts Volume 23 | Supplement 9 | September 2012