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head and neck cancer
1016O PHASE 2, RANDOMIZED TRIAL (CONCERT-2) OF
PANITUMUMAB (PMAB) PLUS RADIOTHERAPY (PRT)
COMPARED WITH CHEMORADIOTHERAPY (CRT) IN
PATIENTS (PTS) WITH UNRESECTED, LOCALLY ADVANCED
SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK
(LASCCHN)
J. Giralt 1 , J.M. Trigo 2 , S. Nuyts 3 , E.M. Ozsahin 4 , K. Skladowski 5 , G. Hatoum 6 ,
J. Daisne 7 , A. Zhang 8 , K. Oliner 9 , A. Vanderwalde 10
1 Radiation Oncology, Vall d`Hebron University Hospital, Barcelona, SPAIN,
2 Medical Oncology, Hospital Universitario Virgen de la Victoria, Malaga, SPAIN,
3 Radiation Oncology, University Hospitals Leuven, Leuven, BELGIUM, 4 Radiation
Oncology, Lausanne University Medical Center (Centre Hospitalier Universitaire
Vaudois), Lausanne, SWITZERLAND, 5 Radiation Oncology, Centrum Onkologii
Instytut M. Sklodowskiej-Curie, Gliwice, POLAND, 6 Clinical Biomedical Sciences,
Florida Atlantic University, Lake Worth, FL, UNITED STATES OF AMERICA,
7 Radiation Oncology, Clinique & Maternité Ste-Elisabeth, Namur, BELGIUM,
8 Global Biostatistics, Amgen, Thousand Oaks, CA, UNITED STATES OF
AMERICA, 9 Medical Sciences - Ivd, Amgen, Thousand Oaks, CA, UNITED
STATES OF AMERICA, 10 Oncology Therapeutics, Amgen, Thousand Oaks, CA,
UNITED STATES OF AMERICA
Background: We evaluated the safety and efficacy of pmab, a fully human
monoclonal antibody against the epidermal growth factor receptor, by comparing
PRT with CRT in pts with LASCCHN.
Methods: Pts with stage III, IVA, or IVB previously untreated LASCCHN of all sites
excluding the nasopharynx were randomized 2:3 to open-label CRT or PRT. CRT
included 2 cycles of cisplatin 100 mg/m2 during accelerated fractionation
radiotherapy (XRT; 70-72 Gy over 6-6.5 weeks). Pmab included 3 cycles at a dose of
9.0 mg/kg with each cycle administered with XRT. This was an estimation study with
no formal hypothesis testing. The primary endpoint was locoregional control (LRC)
rate at 2 years; key secondary endpoints were progression free survival (PFS), overall
survival (OS), and safety. Preplanned HPV subset analysis (determined by p16
immunohistochemistry) was performed on available samples.
Results: Of 151 treated pts (90 PRT, 61 CRT), 84% were men; median age was 58
years; ECOG PS 0: 64%. Overall, the 2-year LRC rate (95% CI) was 51% (40%-62%)
for PRT and 61% (47%-72%) for CRT. For both PFS (hazard ratio [HR] = 1.73 [95%
CI: 1.07-2.81]; p = 0.03) and OS (HR = 1.59 [95% Cl: 0.91-2.79]; p = 0.10), outcomes
favored the CRT arm. Of 99 pts with tumors evaluable for HPV, 24% were HPV+. In
75 HPV- tumors, a difference was observed in PFS (HR = 2.04 [95% Cl: 1.05-3.96]; p
= 0.04), with trends also favoring CRT in LRC and OS. Overall, dose intensity was
high for all components of therapy in both arms (median relative dose intensity:
100% for pmab and 99% for cisplatin, median XRT dose: 100% in both arms). Grade
3+ adverse events (AEs) occurred in 85% PRT vs 81% CRT pts. Key differences in
grade 3+ toxicity between arms (PRT, CRT) included skin disorders (which is a
composite of skin-related AEs) (35%, 3%), neutropenia (0%, 13%), and febrile
neutropenia (0%, 8%).
Conclusions: Trends favored the CRT arm for the primary endpoint (LRC at 2
years), as well as other measures of efficacy, in this predominantly HPV- LASCCHN
population. Small numbers limit conclusions in the HPV+ group. Both PRT and
CRT appeared well tolerated.
Disclosure: G. Hatoum: Advisory Board Member for AmgenK. Oliner: Amgen
stockA. Vanderwalde: Corporate-sponsored research (Amgen), full-time employee of
AmgenAll other authors have declared no conflicts of interest.
Annals of Oncology 23 (Supplement 9): ix334–ix347, 2012
doi:10.1093/annonc/mds402
1017O PRECLINICAL RATIONAL, SAFETY, AND PRELIMINARY
EFFICACY RESULTS OF WEEKLY EVEROLIMUS,
CARBOPLATIN AND PACLITAXEL AS AN INDUCTION
THERAPY FOR PATIENTS WITH UNRESECTABLE LOCALLY
ADVANCED HEAD & NECK SQUAMOUS CELL CARCINOMA
(CAPRA): A GERCOR-IRC PHASE I/II STUDY
S. Faivre 1 ,C.Dreyer 1 , E. Raymond 1 , J. Fayette 2 , J.P. Delord 3 , M. Gatineau 4 ,
B. Chibaudel 5 , N. Aissat 5 , K. Slimane 6 , C. Le Tourneau 7
1 Oncology Department, Beaujon University Hospital, Clichy, FRANCE, 2 Medical
Oncology, Centre Léon Bérard, LYON, FRANCE, 3 Clinical Resarch Unit, Centre
Claudius-Regaud, Toulouse, FRANCE, 4 Medical Oncology, Hôpital
Saint-Joseph, Paris, FRANCE, 5 Medical Oncology, GERCOR-IRC, Paris,
FRANCE, 6 Oncology, Novartis Pharmaceuticals, Rueil-Malmaison, FRANCE,
7 Department of Medical Oncology, Clinical Trial Unit, Institut Curie, Paris, FRANCE
Background: PI3K/mTOR is a survival pathway that was shown activated in 57-81%
of patients (pts) with head & neck squamous cell carcinoma (HNSCC) and might
drive resistance to cytotoxics.
Methods: We have previously shown synergistic cell-cycle dependent effects between
rapamycin/everolimus and carboplatin, or paclitaxel in HNSCC cells (Aissat 2008).
Based on this preclinical translational rationale, a two-step phase I/II trial was
designed using 9 consecutive weekly (w) cycles of oral everolimus combined with
carboplatin (AUC2) and paclitaxel (60mg/m2) followed by chemoradiotherapy in pts
with untreated locally advanced HNSCC.
Results: A total of 27 pts with stage IV HNSCC (median age 58, range 46-84; ECOG
0-2) have been enrolled in this phase I/II study (42 pts scheduled for the phase II).
Among the 7 pts enrolled in the everolimus dose escalation phase I step, 6 pts were
evaluable for safety (3pts at 30 mg/w and 3pts at 50 mg/w). No dose-limiting toxicity
(defined during the first 4 weeks of treatment) was reported. Transient asymptomatic
grade 3 neutropenia (3 pts), anemia (3 pts), and thrombocytopenia (1 pt) were observed.
The most frequently reported adverse events were mild to moderate asthenia, skin
toxicity, and alopecia. The recommended dose of everolimus for the phase II step was 50
mg/w. So far, among pts treated in the phase I/II, 11/13 objective responses (1CR, 10 PR,
2SD) were observed in evaluable pts. Interestingly, several major responses (ranging -60
to -80% by RECIST) were observed in large necrotic primary tumors and lymph nodes of
>6cm diameters. Preliminary genetic analysis of tumors showed neither KRAS, BRAF,
PI3KCA, nor EGFR mutations in tumors responding to this combination.
Conclusions: Weekly 50 mg everolimus combined with carboplatin and paclitaxel
was well tolerated with no DLT, allowing repeated cycles. Major clinical responses in
pts with bulky, locally advanced and necrotic diseases deserve further evaluation of
this combination in pts with HNSCC. Updated results will be presented at meeting.
Disclosure: S. Faivre: Novartis, honorarium, compensatedE. Raymond: Novartis,
honorarium, compensatedK. Slimane: Novartis, employment, compensatedAll other
authors have declared no conflicts of interest.
1018O SAFETY AND EFFICACY OF CISPLATIN PLUS 5-FU AND
CETUXIMAB IN HPV-POSITIVE AND HPV-NEGATIVE
RECURRENT AND/OR METASTATIC SQUAMOUS CELL
CARCINOMA OF THE HEAD AND NECK (R/M SCCHN):
ANALYSIS OF THE PHASE III EXTREME TRIAL
A. Psyrri 1 , L. Licitra 2 , B. De Blas 3 , I. Celik 4 , J.B. Vermorken 5
1 Internal Medicine Propaedeutic, University of Athens Medical School, Attikon
University Hospital, Athens, GREECE, 2 Head & Neck Medical Oncology Unit,
Istituto Nazionale Tumori, Milan, ITALY, 3 Global Clinical Development Unit
Oncology, Merck KGaA, Darmstadt, GERMANY, 4 Global Research & Early
Development, Merck KGaA, Darmstadt, GERMANY, 5 Department of Medical
Oncology, University Hospital Antwerp, Edegem, BELGIUM
Background: Tumor human papillomavirus (HPV) status is a strong predictor of
survival and response to treatment in patients (pts) with early and locally advanced
oropharyngeal cancer, but its effects in R/M SCCHN remain to be clarified. This
retrospective analysis of data from the EXTREME trial assessed the role of tumor
HPV status in pts with R/M SCCHN receiving cisplatin + 5-FU chemotherapy (CT)
alone or in combination with cetuximab. Material and methods:
Immunohistochemical detection of p16 INK4A was used to determine HPV status:
p16-positive and p16-negative disease is referred to as HPV-positive (HPV+) and
HPV-negative (HPV-) disease, respectively.
Results: 196/222 (88%) pts in the CT + cetuximab and 185/220 (84%) pts in the CT
arm had tissue evaluable for p16. Of these, 91% and 88%, respectively, had HPVtumors.
Among HPV- pts, CT + cetuximab (n = 178) improved overall survival (OS),
progression-free survival (PFS) and overall response rate (ORR), compared with
© European Society for Medical Oncology 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
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