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same CT/RT; Arm B2: 3 cycles of induction TPF followed by CET/RT. A total of 204
deaths (420 ptsincluding the 101 randomized in the phase II part of the study
comparing CT/RT with or w/o induction TPF) were required to detect a HR of death
of 0.675 (A1 + A2 vs. B1 + B2; 2-sided a = 0.05; b = 0.20) and a 10% difference in
G3-4 in-field mucosal toxicity (A1 + B1 vs. A2 + B2).
Results: Accrual was completed (421 pts) in April 2012. By May 2012, 348 patients
were evaluable for toxicity during the planned concomitant treatments. 82% of pts
were male; median age was 60y; PS of 0 (77.8%) or 1 (22.2%). Stage was III (31%) or
IV (69%). Sites of disease were: oral cavity: 21.7%, oropharynx: 54.8%, hypopharynx:
23.5%. Data on G3-4 in-field toxicity (primary endpoint) and compliance to CT/RT
vs CET/RT are shown in table 1.
CT/RT N
215
CET/RT N
133 p
In-field mucositis Grade 3 Grade 4 37% 4% 35% 2% 0.79 0.45
In-field skin reaction Grade 3 Grade 4 13% 1% 20% 1% 0.07 0.58
RT median dose, Gy (range) 70 (8-70) 70 (14-70) 0.32
RT median duration, weeks (range) 7 (1-13) 8 (1-14) 3days 32% 38% 0.22
RT modification due to acute toxicity 37% 40% 0.58
Conclusions: No advantage for CET/RT over CT/RT were observed regarding G3-4
in-field toxicities and feasibility. Pts are still being followed-up to assess OS. Table 1:
Disclosure: All authors have declared no conflicts of interest.
1021PD MODULATION OF THE PERITUMORAL
MICROENVIRONMENT BY CETUXIMAB: A WINDOW
PRE-OPERATIVE STUDY IN PATIENTS WITH SQUAMOUS
CELL CARCINOMA OF THE HEAD AND NECK (SCCHN)
S. Schmitz 1 , M. Hamoir 2 , H. Reychler 3 , M. Magremanne 3 , B. Weynand 4 ,
R. Lhommel 5 , F. Hanin 5 , D. Rommel 6 , N. Michoux 6 , J.P. Machiels 7
1 Head and Neck Surgery and Medical Oncology, Cliniques Universitaires
Saint-Luc, Brussels, BELGIUM, 2 Head and Neck Surgery, Cliniques
Universitaires St-Luc, Brussels, BELGIUM, 3 Maxillofacial Surgery, Cliniques
Universitaires Saint-Luc, Brussels, BELGIUM, 4 Anatomopathology, Cliniques
Universitaires Saint-Luc, Brussels, BELGIUM, 5 Nuclear Medicine, Cliniques
Universitaires St-Luc, Brussels, BELGIUM, 6 Radiology, Cliniques Universitaires
Saint-Luc, Brussels, BELGIUM, 7 Medical Oncology, Cliniques Universitaires
St. Luc, Brussels, BELGIUM
Background: Only a subset of SCCHN pts benefits from anti-EGFR mAbs. Trials
with pre- and post-therapy tumor biopsies (windows studies) in treatment-naïve
patients are crucial to better characterize the molecular pathways involved in
treatment response or resistance.
Methods: Cetuximab (C) (400mg/m2 first wk followed by 250mg/m2/wk) was given
pre-operatively during 2 wks (day -15 until day -1, 3 infusions) before surgery (day
0) to 20 treatment-naïve SCCHN pts selected for primary curative surgery. As
controls, 5 additional pts were included without C treatment but with the same
requirements regarding biopsies and imaging. Tumour biopsies, FDG/PET, and CT
were performed at diagnosis and surgery. The aims of the study were (i) safety,
(ii) C activity by FDG-PET (Po = 0.10, P1 = 0.35, a = 0.05 and b= 0.10) and (iii)
translational research. We compared pathologic changes in surgical specimens of the
C group with control specimens and correlated these results with microarray analysis
performed on paired biopsies in the C group.
Results: C infusion given 24 hrs before surgery was safe. 90 % had a FDG-PET
partial response (PR) (EORTC guideline) in the C group vs 0% in the controls. 52%
had a ΔSUVmax decrease of >50%. In surgical specimens we detected modifications
of the peritumoral environment. By immunochemistry, we found more fibrosis
arranged in a compact manner in the C group than in the non-treated samples
(histological score) (p = 0.04). Genome-wide expression analysis (Affymetrix HG
U133 Plus 2.0) of the paired biopsies taken in the tumor center before and after C
supports this histological observation. Results show a significant increase in
expression (Student’s T test p = 0.02; n = 20) of a previously published stroma
signature (Finak et al., Breast Cancer Res 2006) after C. A trend was also observed
between this stroma signature score and the fibrosis histological score.
Conclusions: Pre-operative study with C is safe. Our findings suggest that C induces
quantitative modifications in the microenvironment of the tumor. We are currently
investigating other components of the peri-tumoral environment (inflammation and
vascularization).
Disclosure: J.P. Machiels: consultant/advisory role: Boehringer IngelheimAll other
authors have declared no conflicts of interest.
Annals of Oncology
1022PD PHASE II STUDY OF PEMETREXED PLUS CISPLATIN AND
CETUXIMAB IN ADVANCED SQUAMOUS CELL CARCONIMA
OF THE HEAD AND NECK
J.B. Vermorken 1 , T.C. Gauler 2 , J. Stoehlmacher-Williams 3 , A. Dietz 4 , J.M. Lopez-
Picazo 5 , O. Hamid 6 , A.M. Hossain 6 , T. Burkholder 6 , S. Chang 6 , L. Licitra 7
1 Department of Oncology, U.Z.A. University Hospital Antwerp, Edegem, BELGIUM,
2 Oncology, University Hospital, Essen, GERMANY, 3 Oncology, University
Hospital Dresden, Dresden, GERMANY, 4 Oncology, Universitatsklinikum Leipzig,
Leipzig, GERMANY, 5 Oncology, Clinica Universidad de Navarra, Pamplona,
SPAIN, 6 Oncology, Eli Lilly and Company, Indianapolis, IN, UNITED STATES OF
AMERICA, 7 Oncology, Instituto Nazionale Tumori, Milan, ITALY
Background: Patients (pts) with recurrent or metastatic SCCHN have a very poor
prognosis. Platinum-based chemotherapy has long been standard treatment. Adding
cetuximab to cisplatin-based combinations has improved overall survival (OS) and is
currently standard treatment in SCCHN. In a phase III study, pemetrexed has shown
benefit in SCCHN, particularly in performance status (PS) 0-1 pts.
Patients and methods: Pts who had no more than 1 prior systemic therapy for
locally-advanced disease received cetuximab 250 mg/m 2 (loading dose:400 mg/m 2 ),
pemetrexed 500 mg/m 2 , with vitamin supplementation, and cisplatin 75 mg/m 2 day
1, up to 6 cycles. Pts completing at least 4 cycles had the option to receive
maintenance with pemetrexed and cetuximab, or monotherapy, if toxicity occurred.
Primary objective was progression-free survival (PFS); secondary objectives were OS,
overall response rate (ORR) and safety. Sixty-five patients were needed to meet an
objective median PFS of 5.5 months (mos.), with 90% power; 2-sided α of 0.05.
Results: Sixty-six Caucasians (53 male), median age of 62 years (42-87) received at least
1 dose of therapy. Nineteen pts had a PS of 0; 47 pts had a PS of 1. Median cycles
received = 5.0 (1-27). Median PFS was 4.4 mos. (95% CI: 3.6, 5.4); median OS was 9.7
mos. (95% CI: 6.5, 13.1). Fifty-eight pts were evaluable for ORR analysis. ORR was 29.3%
(95% CI: 18.1, 42.7); 1 complete response (1.7%); 16 partial responses (27.6%); 20 pts had
stable disease (34.5%). An exploratory subgroup analysis showed larynx tumor pts had
greater improvement in survival than non-larynx pts; median OS = 20.8 mos.(HR = 0.44;
95% CI= 0.20, 0.95); p = 0.032. Drug-related grade 3/4 toxicities included leukopenia
(34.8%), neutropenia (33.4%), fatigue (24.2%), anorexia (12.1%) and hypomagnesemia
(10.6%). There were 5 drug-related deaths (7.6%) on treatment (respiratory failure = 2;
implant site hemorrhage = 1, sepsis = 1; death, not otherwise specified = 1).
Conclusions: Efficacy results were consistent with current standard treatment for
SCCHN, but the pre-specified goal of median PFS of 5.5 mos. was not met.
Although toxicities were consistent with the safety profiles of this combination, there
were 5 deaths on treatment.
Disclosure: J.B. Vermorken: Dr. Jan B. Vermorken is a member of an advisory board
for Merck-Serono, Amgen, Boehringer-Ingelheim, Genentech and Sanofi-Aventis and
has lectured (compensated) for Merck-Serono, Amgen, Bristol-Byers Squibb and
Sanofi-Aventis.T.C. Gauler: Dr. Gauler is an Advisory board member and received
honoraria from Eli Lilly and Company.J. Stoehlmacher-Williams:
Dr. J. Stoehlmacher-Williams received honoraria for an advisory board and
presentations, travel support and various translational research grants from Eli Lilly
and Company.J.M. Lopez-Picazo: Dr. Lopez-Picazo is an advisory board member for
Eli Lilly and Company.O. Hamid: Dr. Hamid is an employee of Eli Lilly and
Company and has stock ownership.A.M. Hossain: Anwar Hossain is an employee of
Eli Lilly and Company and has stock ownership.T. Burkholder: Tiana Burkholder is
an employee of Eli Lilly and Company and has stock ownership.S. Chang: Dr. Chang
is an employee of Eli Lilly and Company and has stock ownership.L. Licitra: Dr.
Licitra served as an advisory board member and received research sponsorship from
Eli Lilly and Company.All other authors have declared no conflicts of interest.
1023PD TEMSIROLIMUS IS ACTIVE IN REFRACTORY SQUAMOUS
CELL CARCINOMA OF THE HEAD AND NECK (SCCHN)
FAILING PLATINUM-BASED CHEMOTHERAPY AND
CETUXIMAB: EFFICACY AND TOXICITY DATA FROM THE
PHASE II TEMHEAD STUDY
V. Grünwald 1 , U. Keilholz 2 , A. Boehm 3 , O. Guntinas-Lichius 4 , B. Hennemann 5 ,
H.J. Schmoll 6 , P. Ivanyi 1 , A. Zörner 7 , A. Zapf 8 , T.C. Gauler 9
1 Clinic for Hematology, Hemostaseology, Oncology, Hannover Medical School,
Hannover, GERMANY, 2 Hematology & Oncology, Charite, Berlin, GERMANY,
3 Clinic and Policlinic for Ear, Nose and Thorat, Universitätsklinikum Leipzig,
Leipzig, GERMANY, 4 Clinic for Ear, Nose and Throat, Universitätsklinikum Jena,
Jena, GERMANY, 5 Clinic for Heamatology and Medical Oncology, Ev. Bethesda-
Johanniter Klinikum GmbH, Duisburg, GERMANY, 6 Dept. Hematology/
Oncology, University of HalleMartin Luther University Hospital, Halle, GERMANY,
7 Clinical Pharmacology, Medical School Hannover, Hannover, GERMANY,
8 Biostatistics, Medical School Hannover, Hannover, GERMANY, 9 Dept. Int.
Medicine (Cancer Research), University Hospital EssenWestdeutsches
Tumorzentrum, Essen, GERMANY
Background: Prognosis of patients with failure of cisplatin-based 1st line
chemotherapy for recurrent or metastatic SCCHN remains poor. We therefore
evaluated temsirolimus after failure of cisplatin and cetuximab in SCCHN.
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