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Annals of Oncology
1522PD A MULTI-CENTER PHASE II CLINICAL TRIAL OF THE
CHIMERIC ANTI-MESOTHELIN MONOCLONAL ANTIBODY
AMATUXIMAB IN COMBINATION WITH CHEMOTHERAPY
FOR FRONTLINE THERAPY OF MALIGNANT PLEURAL
MESOTHELIOMA: UPDATED CLINICAL OUTCOMES AND
CORRELATIVE STUDIES
M. Reck 1 , R. Hassan 2 , T. Jahan 3 , H.L. Kindler 4 , L. Bazhenova 5 ,P.Fatato 6 ,J.
W. Heyburn 6 , J. Parno 6 , J.D. Maltzman 6 , B. Wallin 6
1 Thoracic Oncology, Krankenhaus Grosshansdorf, Grosshansdorf, GERMANY,
2 Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, MD,
UNITED STATES OF AMERICA, 3 Division of Hematology/Oncology, University of
California - San Francisco, San Francisco, CA, UNITED STATES OF AMERICA,
4 University of Chicago, Division of Oncology, Chicago, IL, UNITED STATES OF
AMERICA, 5 Health Sciences, UCSD Moores Cancer Center, La Jolla, UNITED
STATES OF AMERICA, 6 Oncology, Morphotek, Exton, PA, UNITED STATES OF
AMERICA
Background: Amatuximab (MORAb-009) is a chimeric monoclonal antibody to
mesothelin, a cell surface glycoprotein highly expressed in malignant mesothelioma
(MPM). Based on amatuximab results in a phase I clinical trial and pre-clinical
studies showing synergy in combination with chemotherapy, a single arm phase II
study of amatuximab plus pemetrexed (P) and cisplatin (C) was initiated in MPM
patients (Pts).
Methods: Eligibility criteria: unresectable epithelial or biphasic MPM, no prior
chemotherapy and Karnofsky Performance Status (KPS) >70%. Pts received
amatuximab 5 mg/kg on days 1 and 8 with P 500 mg/m 2 and C 75 mg/m 2 (PC)
given on day 1 of each 21-day cycle for 6 cycles. Pts with objective response or stable
disease received amatuximab monotherapy until disease progression. Primary
endpoint: progression-free survival (PFS) at 6 months (mo). Secondary endpoints:
overall survival (OS), objective response rate (ORR), pulmonary function (PFT), and
safety of amatuximab with PC.
Results: 89 pts with unresectable MPM were enrolled at 26 sites. Pt characteristics:
median age 67 yrs (range 46-80); 78% male; 70% with KPS >90%; 89% epithelial
MPM, 11% biphasic MPM; 88% had stage III/IV disease. Median PC-amatuximab
cycles: 5 (range 1-6). 56 (63%) pts subsequently received single agent amatuximab. In
addition to expected toxicities from PC, hypersensitivity reactions (12.4%; Grade 3/4
= 5%) from amatuximab were noted. By independent radiological review, 30 pts
(39%) had a partial response and 39 (51%) had stable disease. PFS at 6 mo: 52%
(95% CI: 39.5-63.5). Median PFS = 6.1 mo (95% CI: 5.4-6.5). Median OS = 14.8 mo
(95% CI: 12.4 – 19.2). 29 pts are alive and 5 pts are still receiving maintenance
amatuximab. The mean Forced Vital Capacity (FVC) change from baseline was
132ml. The proportion of pts with an FVC improvement of > 400ml was 23%.
Conclusions: Amatuximab in combination with PC was generally well-tolerated in
this study in MPM pts with a disease control rate of 90%. The median OS of 14.8
months compares favorably with historical controls.
Disclosure: M. Reck: Advisory Board (compensated): Hoffmann-La Roche, Lilly,
AstraZeneca, Pfizer, Daiichi-Sankyo, BMS. Honoraria for lectures: Hoffmann-La
Roche, Lilly, AstraZeneca, Daiichi-SankyoT. Jahan: research funding from Genentech,
Lilly and PfizerH.L. Kindler: research funding for morphotekP. Fatato: Employee of
MorphotekJ.W. Heyburn: Employee of MorphotekJ. Parno: Employee of MorphotekJ.
D. Maltzman: Employee of MorphotekB. Wallin: Employee of MorphotekAll other
authors have declared no conflicts of interest.
1523P THE 8.1 ANCESTRAL HAPLOTYPE IS STRONGLY
ASSOCIATED WITH THE RISK OF SMALL CELL LUNG
CANCER
J. Kocsis 1 ,L.Graf 1 , A. Szilagyi 2 , B. Dome 3 , L. Tamasi 4 , G. Galffy 4 , Z. Orosz 5 ,
Z. Prohaszka 2 , G. Fust 2 , Z. Bartfai 6
1 3rd Dept of Internal Medicine, Oncology, Semmelweis University, Budapest,
HUNGARY, 2 3rd Dept of Internal Medicine, Semmelweis University, Budapest,
HUNGARY, 3 Tumor Biology, National Koranyi Institute of Pulmonology,
Budapest, HUNGARY, 4 Pulmonology, Semmelweis University, Budapest,
HUNGARY, 5 Radiology and Oncotherapy, Semmelweis University, Budapest,
HUNGARY, 6 Pulmonology, Erzsebet Hospital, Sopron, HUNGARY
Background: It is well established that the risk of lung cancer is related to the
individual genetic background as it is reflected in the increased incidences among
first degree relatives. The discovery of these genetic variations can lead to the
identification of those individuals who are at high risk of developing lung cancer.
AH8.1 is a haplotype which extends through the whole MHC region in the short
arm of chromosome 6. It is the most frequent and a very conservative haplotype in
the Caucasian population. Previously we have reported a strong association between
AH8.1 and colorectal cancer with an odds ratio higher than any risks reported for
SNPs in genome-wide association studies or candidate gene studies. Published data
indicate that AH8.1 is a strong risk factor for ovarian cancer and for non-Hodgkin
lymphoma as well.
Aim/methods: Here we have determined the carrier state of AH8.1 in 102
patients with small cell lung cancer (SCLC) (62 + 7.8 years), 94 patients with
non- SCLC (NSCLC) (59+ 8.6 years) and in 248 age-matched control subjects
(66.7 + 6.5 years). Subjects carrying all the four marker alleles of AH8.1 (C allele
of AGER 429T > C, G allele of HSP70-2 1267A > G, A allele of TNFalpha -308G
> A, as well as G allele of LTA 252A > G polymorphisms) were considered as
AH8.1 carriers.
Results: 23% (23/102) of SCLC patients, 13.8% (13/94) of NSCLC patients, and 13%
(32/248) of healthy controls carried the AH8.1 haplotype. We have found a
significant increased risk for SCLC in those people carrying AH8.1 with an odds
ratio of 1.94 (1.01-3.73; p = 0.046) (for men: 3.09, 1.07-8.82; p = 0.031). However,
there was no significant increase in the risk for NSCLC.
Summary: These findings indicate that carriers of the AH8.1 haplotype are at
increased risk for SCLC and it can be due to the altered immune response that is
characteristic for 8.1 AH.
Disclosure: All authors have declared no conflicts of interest.
1524P COMBINATION OF THREE CYTOTOXIC AGENTS IN SMALL
CELL LUNG CANCER
G. Stathopoulos 1 , D. Traphalis 1 , J. Dimitroulis 2 , C. Kosmas 3 , J. Stathopoulos 1 ,
D. Tsavdaridis 4
1 A’ Oncology Clinic Errikos Dunant, Dr. Georgios Stathopoulos, Athens,
GREECE, 2 6th Pneumonic Clinic, Hospital for Thoracic Disease, Athens,
GREECE, 3 Oncology Clinic, Anticancer Hospital Piraeus, Piraeus, GREECE,
4 Oncology Clinic, Anticancer Hospital, Thessaloniki, GREECE
Background: Small-cell lung cancer treatment has been tested by using combinations
of several cytotoxic agents. For quite a number of years, the established treatment has
been cisplatin and etoposide as the most effective chemotherapy regimen. Paclitaxel
has also been used in combination with cisplatin and etoposide; the latter three -
drug treatment has been effective but unacceptable due to toxicity.
Patients and methods: In the present trial we tested the aforementioned three-drug
combination and avoided the toxicity in the majority of the patients by administering
all 3 drugs on day 1 instead of on the established three days of treatment. Fifty patients
were recruited from 5 oncology clinics. All patients had histologically- or cytologicallyconfirmed
small-cell-lung cancer with limited and extensive disease in 40% and 60% of
the patients respectively. Treatment was as follows: cisplatin 75mg/m 2 , etoposide
120mg/m 2 with no dosage higher than 200mg/m 2 and paclitaxel 135mg/m 2 . The agents
were administered on day 1 and repeated every three weeks for 6 cycles in total.
Results: The median survival was 14 months (95% CI 10.6-17.4) Forty-five patients
(90%) achieved a response: 20(40%) patients a complete response and 25 (50%) a
partial response. Adverse reactions was grade 3 and 4 neutropenia in 12% and 2% of
the patients, respectively. Other side effects involved very low toxicity.
Conclusion: The one-day three-agent (cisplatin, etoposide, paclitaxel) treatment of
small-cell lung cancer is beneficial with respect to response rate and survival, and has
low and well-tolerated toxicity.
Disclosure: All authors have declared no conflicts of interest.
1525P THIRD-LINE CHEMOTHERAPY IN SMALL CELL LUNG
CANCER: AN INTERNATIONAL ANALYSIS
D. Simos 1 , G. Sajjady 2 , M. Sergi 3 , M.S. Liew 4 , R. Califano 5 ,C.Ho 2 , N.B. Leighl 3 ,
S. White 4 , Y. Summers 5 , P. Wheatley-Price 1
1 Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, ON, CANADA,
2 Medical Oncology, British Columbia Cancer Agency, Vancouver, BC, CANADA,
3 Medical Oncology, Princess Margaret Hospital, Toronto, ON, CANADA, 4 Austin
Health, Joint Austin-Ludwig Oncology Unit, Victoria, AUSTRALIA, 5 Medical
Oncology, The Christie NHS Foundation Trust & University Hospital South
Manchester NHS Foundation Trust, Manchester, UNITED KINGDOM
Background: Small cell lung cancer (SCLC) is an aggressive disease and
chemotherapy (CT) is the mainstay of treatment. Despite good response rates most
patients (pts) will relapse and die of this disease. Standard 1st-line CT in limited
(LD) and extensive stage disease is usually etoposide with platinum (P) or CAV
(cyclophosphamide, doxorubicin, vincristine). At progression, 2nd-line CT may
involve re-challenging with the 1st-line regimen. For pts who progress after 2 lines of
CT, there is little evidence to guide treatment decisions, and the benefit of 3rd-line
CT is unclear.
Objective: To determine the clinical benefit of 3rd-line CT for SCLC.
Study design: An international multi-centre retrospective analysis of pts who
received 3 lines of CT for SCLC from 2001-2011 was performed. Baseline
demographics, known prognostic factors and CT details were recorded. The main
end-points were response rate (RR) and overall survival (OS) after 3rd-line CT.
Results: A total of 124 eligible pts were identified; 59% male, median age 61, 89%
ECOG 0-1, 40% LD. First-line P-based CT was given to 99% of pts, with a RR of
90%. In the 2nd-line, 70 pts (56%) were re-challenged with similar CT, with the
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds415 | ix493