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GlaxoSmithKline (myself, compensated); Daiichi-Sankyo, Merrimack (myself,
uncompensated). J.M. Wigginton: Employment or Leadership Role: Bristol-Myers
Squibb (employment, myself, compensated). Stock Ownership: Bristol-Myers Squibb
(myself). G. Kollia: Employment or Leadership Role: Bristol-Myers Squibb
(employment, myself, compensated). Stock Ownership: Bristol-Myers Squibb
(myself). A. Gupta: Employment or Leadership Role: Bristol-Myers Squibb
(employment, myself, compensated). Stock Ownership: Bristol-Myers Squibb
(myself). All other authors have declared no conflicts of interest.
1238PD ACTIVE SPECIFIC IMMUNOTHERAPY WITH
RACOTUMOMAB IN THE TREATMENT OF ADVANCED
A. Macías 1 , S. Alfonso 2 , E. Santiesteban 3 , C. Viada 1 , I. Mendoza 4 , P.P. Guerra 4 ,
R.E. Gómez 5 , M.L. Ardigo 5 , A.M. Vázquez 1 , R. Pérez 1
1 Clinical Department, Center of Molecular Immunology, Havana, CUBA,
2 Oncology Unit, University Hospital “Celestino Hernánez Robau”, Las Villas,
CUBA, 3 Oncology Unit, Hospital “José Ramón Tabranes”, Matanzas, CUBA,
4 Project Management and Monitoring, National Clinical Trial Coordinator Center,
Havana, CUBA, 5 Clinical Research, Elea Laboratories, Buenos Aires, ARGENTINA
Background: Gangliosides, especially NeuGc-GM3, are an attractive target for cancer
immunotherapy. They do not express in normal human cells but are overexpressed
in several solid tumors including NSCLC and are involved in tumor development
and growth. Racotumomab is therapeutic vaccine which induces a cellular and
humoral immune response against NeuGc-GM3 expressed in tumors. Phase I and II
trials in melanoma, breast and lung cancer have shown the low toxicity and high
immunogenicity of racotumomab.
Methods: Multicenter, randomized, placebo controlled, double blind clinical trial in
patients with advanced (IIIB and IV) NSCLC who had an ECOG status ≤ 2 and had
achieved partial or complete response or disease stabilization after completion of
onco-specific treatment. 176 patients were randomized 1:1 to placebo or
racotumomab. Initially 1 dose was administered every 14 days (induction period, 5
doses in total), followed by 1 dose every 28 days (maintenance period) until patient
refusal or worsening of ECOG status.
Results: Safety: The most common adverse events were expected mild reactions at the
injection site (pain and itching). No differences were observed between both groups.
Overall Survival (OS): Intent to Treat Analysis (ITT): Survival since inclusion was 15.7
months (mean) and 8.3 months (median) in the racotumomab arm and 10.6 months
(mean) and 6.3 months (median) in the placebo arm (log rank test, p= 0.02). OS rate
(%) at 12 and 24 months was 38 % and 17 % in the racotumomab arm and 24 % and
7 % in the placebo arm. Per Protocol Population Analysis (PPP): Includes patients
who received ≥ 5 doses of racotumomab/ placebo (135/174 patients, 77% of the patient
population). Survival since inclusion was 18.9 months (mean) and 10.9 (median) in
the racotumomab arm and 11.4 months (mean) and 6.9 months (median) in the
placebo arm (log rank test, p= 0.002). OS rate (%) at 12 and 24 months: 48 % and 22
% in the racotumomab arm and 28 % and 8 % in the lacebo arm.
Conclusions: Immunization with racotumomab is safe. There is an OS benefit for
racotumomab, both in the ITT and PPP analyses. Survival benefit appears to be
increased when the patient’s clinical condition allows completion of the induction
period of vaccination.
Disclosure: R.E. Gómez: Is a full time employee at Elea Laboratories. M.L. Ardigo: Is a full
time employee at Elea Laboratories. All other authors have declared no conflicts of interest.
1239P CLINICAL GENOTYPING AND EFFICACY OUTCOMES:
EXPLORATORY BIOMARKER DATA FROM THE PHASE II
ABIGAIL STUDY OF 1ST-LINE BEVACIZUMAB +
CHEMOTHERAPY IN NON-SQUAMOUS NON-SMALL-CELL
LUNG CANCER (NS-NSCLC)
C. Pallaud 1 , M. Reck 2 , E. Juhasz 3 , B. Szima 4 ,C.Yu 5 , O. Burdaeva 6 , S. Orlov 7 ,
S.J. Scherer 8 , V. Archer 9 , T.S.K. Mok 10
1 Pharma Development Oncology Department, F. Hoffmann-La Roche Ltd, Basel,
SWITZERLAND, 2 Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf,
GERMANY, 3 Pulmonology Department Xiv, Országos Korányi TBC és
Pulmonológiai Intézet, Budapest, HUNGARY, 4 Pulmonology Department,
Markusovszky Hospital Oncoradiology, Szombathely, HUNGARY, 5 Department of
Internal Medicine, National Taiwan University Hospital, Taipei, TAIWAN,
6 Chemotherapy Department, Arkhangelsk Regional Oncology Center,
Arkhangelsk, RUSSIAN FEDERATION, 7 Laboratory of Thoracic Oncology, St
Petersburg State Medical University, St. Petersburg, RUSSIAN FEDERATION,
8 Pharma Development Department, Genentech, San Francisco, CA, UNITED
STATES OF AMERICA, 9 Clinical Development (oncology), Roche Products Ltd.,
Welwyn Garden City, UNITED KINGDOM, 10 Department of Clinical Oncology,
Chinese University of Hong Kong Prince of Wales Hospital, Shatin, Hong Kong, CHINA
Background: ABIGAIL (BO21015; NCT00700180) is a phase II, randomized,
multicentre study exploring correlation between biomarkers (BMs) and best overall
response (BOR) to bevacizumab with carboplatin/gemcitabine (CG) or carboplatin/
paclitaxel (CP) in chemonaïve patients with advanced/recurrent ns-NSCLC.
Annals of Oncology
ABIGAIL efficacy, safety and plasma baseline results have been reported. This
abstract presents exploratory clinical genotyping data from this study.
Methods: 303 patients with untreated advanced/recurrent ns-NSCLC were
randomized 1:1 to receive bevacizumab 7.5 mg/kg or 15 mg/kg until progression or
unacceptable toxicity (with 6 cycles of CG or CP). Patients who consented provided
blood and tumour samples for BM analysis. Exploratory analyses were conducted to
assess whether genetic variants in the VEGFA pathway may act as biomarkers for
efficacy and safety. Here we report data from DNA analysis for 12 single-nucleotide
polymorphisms (SNPs) across 3 genes: VEGFA (5 SNPs), VEGFR-1 (3 SNPs) and
VEGFR-2 (4 SNPs). SNPs were identified using specific individual genotyping assays.
Results: VEGFA: c. + 405/c.-634 (CG), VEGFA: c.-460T > C; c. -1498T > C (CT) and
VEGFA: c.-2578 C > A (AC) were all associated with >50% higher odds of
responding to treatment. VEGFR-1 rs9554316 (GT) was associated with >30% higher
risk of progression and >40% higher risk of death. VEGF: c. + 936 C > T (CT) was
associated with higher incidence of hypertension. When p-values were adjusted for
treatment and prognostic factors, no SNPs were associated with significantly higher
risk of hypertension.
Conclusions: One SNP was associated with increased risk of progression/death, while
3 others were associated with increased BOR. However, adjustment for multiple
testing would no longer result in statistically significant p-values. SNPs analysed in
this study have been previously reported as showing potential predictive value in
other studies: VEGFA SNPs in breast cancer (E2100) and NSCLC (E4599); VEGFR1
SNP in pancreatic cancer (AVITA). More exploratory analyses from this and other
trials of bevacizumab may provide further insight.
Disclosure: C. Pallaud: Own stock in and currently employed by F. Hoffmann-La
Roche Ltd. M. Reck: Attended advisory boards for Roche, Lilly, BMS, AstraZeneca
and Daiichi Sankyo. Received honoraria for lectures from Roche, Lilly, Daiichi
Sankyo and AstraZeneca. B. Szima: Received funding for research. C. Yu: Attended
advisory boards for Roche, AstraZeneca, Takeda and Pfizer. S.J. Scherer: Currently
employed by Roche/Genentech. V. Archer: Currently employed by Roche. T.S.K.
Mok: Attended advisory boards for AstraZeneca, Roche, Eli Lilly, Merck Serono,
Eisai, BMS, BeiGene, AVEO, Pfizer, Taiho, BI and GSK Biologicals. On the IASLC
board of directors. Received research funding from AstraZeneca. All other authors
have declared no conflicts of interest.
1240P CIRCULATING ENDOTHELIAL CELLS (CEC), CIRCULATING
ENDOTHELIAL PROGENITORS (CEP) AND CIRCULATING
TUMOUR CELLS (CTC) AS MARKERS FOR RESPONSE TO
BEVACIZUMAB/CARBOPLATIN/PACLITAXEL (B + CP) OR
BEVACIZUMAB/ERLOTINIB (B + E) IN ADVANCED
NON-SQUAMOUS NON-SMALL-CELL LUNG CANCER
(NS-NSCLC)
F. Farace 1 , S. Le Moulec 2 , J. Mazieres 3 , H. Senellart 4 , E. Dansin 5 ,
A. Madroszyk 6 , X. Quantin 7 , H. Berard 8 , B. Besse 9
1 Laboratory of Translational Research, Institut Gustave Roussy, Villejuif, FRANCE,
2 Department of Oncology, Hôpital d’Instruction des Armées du Val-de-Grâce,
Paris, FRANCE, 3 Department of Thoracic Oncology, Hôpital De Larrey, Toulouse,
FRANCE, 4 Department of Medical Oncology, Institut de Cancérologie de l’Ouest
Site René Gauducheau, Nantes, FRANCE, 5 Department of Medical of Oncology,
CLCC Oscar Lambret, Lille, FRANCE, 6 Department of Medical Oncology, Institut
Paoli Calmettes, Marseille, FRANCE, 7 Department of Thoracic Oncology, Hôpital
Arnaud de Villeneuve, CHU de Montpellier, Montpellier, FRANCE, 8 Department
of Pnuemology, Hôpital d’Instruction des Armées Sainte Anne, Toulon, FRANCE,
9 Departement of Medicine, Institute Gustave Roussy, Villejuif, FRANCE
Background: The phase II, open-label BRAIN study (ML21823; NCT00800202) is
the first to assess the efficacy/safety of bevacizumab combined with chemotherapy in
patients (pts) with ns-NSCLC and untreated CNS metastases. Investigation of CEC,
CEP or CTC levels as potential markers of response to bevacizumab was undertaken.
Methods: In the B + CP arm, blood samples were taken before treatment on day 1
(d1) of cycle 1 (C1) (and 6 hrs after [C1 + 6h] treatment at one centre only), and on
d1 of C2 and C3, i.e. 4 samples in total. Samples were taken for the B + E arm on d1
of C1, C2 and C3 (3 samples total). CEC and CTC levels were measured with
CellSearch (Immunicon, Veridex). CEP were measured using four-colour flow
cytometry after enrichment of progenitor cells using Miltenyi Biotec EPC
enumeration and enrichment kit. Cut-offs were 15 cells/4mL for CEC, 2 cells/7.5mL
for CTC and median for CEP. Relation between marker levels and 6-month
progression-free rate (PFR) and best overall response (BOR) was examined.
Results: CEC and CTC were analysed in 69/91 (76%) pts, and CEP in 32/91 (35%)
pts; baseline (BL) characteristics were similar to the overall population. CEC, CTC
and CEP were detected at BL in 94%, 94% and 100% of these pts. In the B + CP
group, CEC levels were increased at C1 + 6h, possibly reflecting the antivascular effect
of chemotherapy. Furthermore, in the B + CP group, pts with higher BL CTC and no
peak in CEC levels at C1 + 6h progressed at 6 months. Analysis of association of
markers with BOR and PFR for the two regimens is ongoing.
Conclusions: Measuring CEC, CTC and CEP is feasible in NSCLC. Detailed analyses
will be presented. The clinical value of these markers for predicting response to
bevacizumab in advanced ns-NSCLC patients warrants further investigation.
ix406 | Abstracts Volume 23 | Supplement 9 | September 2012