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MERCK SERONO: Advisor, speaker in symposia, research grant PFIZER: Advisor
ROCHE/GENENTECH: Advisor, speaker in symposia. R. Pirker: The author declares
the following: Honoraria for Advisory Board and speaker’s fee from AstraZeneca,
Boehringer Ingelheim, Merck Serono and Roche. K.J. O’Byrne: The author declares:
Payment from Merck Serono in relation to a protocol writing committee and
advisory boards and travel costs in related to attendance. Honoraria from Merck
Serono associated with presentation of data at satellite/company symposia. K.M.
Kerr: Keith Kerr has acted on Advisory Boards and has received speaker’s fees from
Merck Serono. He has had similar roles with Astra Zeneca, Roche, Eli Lilly, Daichi
Sankyo, Pfizer, Boeringher Ingelheim and Glaxo Smith Klein. S. Störkel: The author
has been involved in sponsored research by Merck KGaA. I. Celik: The author is an
employee of Merck KGaA. A. von Heydebreck: Teh author is an employee of Merck
KGaA and declares stock ownership in this company. F.A. Shepherd: Honorarium
from Merck KGaA for presentation at Scientific, Industry-sponsored Satellite
Symposium. Provided compensated consultation services to Merck KGaA.
1273P T790M RESISTANT MUTATION IN PLASMA OF ACQUIRED
RESISTANT EGFR MUTATED NON SMALL CELL LUNG
CANCER (NSCLC) PATIENTS - THE TARZO TRIAL
(NCT00503971)
N. Reguart 1 , E. Nadal 2 , M.A. Molina 3 , E. Carcereny 4 , C. Queralt 4 , A. Insa Molla 5 ,
I. Aguirre 6 , M. Taron 7 , D. Isla Casado 8 , R. Rosell 9
1 Medical Oncology, Hospital Clinic Barcelona, BARCELONA, SPAIN, 2 Medical
Oncology, Hospital Duran i Reynals (ICO), Barcelona, SPAIN, 3 Laboratoy of
Biology Department, Pangaea Biotech, USP Dexeus University Institute,
Barcelona, SPAIN, 4 Medical Oncology Service, Hospital Germans Trias i Pujol
(ICO), Badalona, SPAIN, 5 Medical Hematology and Oncology, Hospital Clinico
Universitario de Valencia, Valencia, SPAIN, 6 Medical Oncology, Hospital
Germans Trias i Pujol, Barcelona, SPAIN, 7 Medical Oncology, Hospital Germans
Trias i Pujol (ICO), Barcelona, SPAIN, 8 Oncology Service, Hospital Clínico
Universitario Lozano Blesa, Zaragoza, SPAIN, 9 Medical Oncology, Hospital
Germans Trias i Pujol (ICO)Oncology, Badalona, SPAIN
Background: EGFR-mutant NSCLC patients (pts) ultimately overcome resistant to
tyrosine kinase inhibitors (TKIs). Among resistant mechanisms secondary EGFR
T790M is the most frequent and account 50% of tumors. Previous data suggest that
tumors with acquired T790M at post-progression biopsy specimen may have a more
favorable prognosis and indolent progression. However, tumor re-biopsies at
progression sites are scare in NSCLC patients and blood samples are a non-invasive
method that may help to identify resistant mechanisms.
Material and methods: Pts with advanced NSCLC harboring EGFR mutations (Exon
19 and 21) and acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) were
eligible. All patients where included in a phase II trial (TARZO) and treated with
erlotinib 150 mg PO daily plus oral vorinostat 400 mg QD on days 1–7 and 15–21 in
a 28-day cycle. Blood samples were required at study entry. We aim to determine the
feasibility and incidence of T790M resistant mutation from plasma DNA from
patients by mutation from cell free circulating DNA from patients using a 5 0 nuclease
PCR assay (TaqMan assay) with a FAM MGB-labeled probe for the wild-type and a
VIC MGB-labeled probe for the mutant sequence in the presence of a protein
nucleic acid (PNA) clamp, which was designed to inhibit the amplification of the
wild-type allele (Pangaea Biotech SL patent).
Results: Twenty-five pts were included in the trial. From those, nineteen plasma
specimens were obtained and used for DNA extraction. Overall T790M resistant
mutation was detected from plasma DNA in 36.8% of the samples (7/19). There were
no differences according patient characteristics (gender/ECOG-PS, smoking habits,
number of previous treatments) or type of sensitizing mutation in tissue (Exon 19,
L858R) and the presence of T790M. Median time to progression (TTP) and survival
(OS) for the entire cohort was 2.4 months (IC 95% 1.2-3.6) and 13.2 months (IC
95% 2.23-26.9 months). Median TTP and OS were 2.4 vs 1.8 (p 0.076) and 13.7 vs
3.7 (p 0.095) in patients without and with T790M respectively.
Conclusions: T790M mutation is a common feature of resistant acquired EGFR
mutated NSCLC patients and can be detected using plasma DNA.
Disclosure: All authors have declared no conflicts of interest.
1274P ALK AND EGFR MUTATION ANALYSIS IN A PHASE II TRIAL
OF CISPLATIN/PEMETREXED IN JAPANESE PATIENTS WITH
ADVANCED NON-SQUAMOUS NON-SMALL CELL LUNG
CANCER
N. Yanagitani 1 , K. Kaburaki 1 , F. Ohyanagi 1 , K. Kudo 1 , A. Horiike 1 , N. Motoi 2 ,
K. Takeuchi 2 , Y. Ishikawa 2 , T. Horai 1 , M. Nishio 1
1 Thoracic Oncology Center, Cancer Institute Hospital, Japanese Foundation for
Cancer Research, Tokyo, JAPAN, 2 Pathology, Cancer Institute Hospital,
Japanese Foundation for Cancer Research, Tokyo, JAPAN
Background: Recently, ethnic differences and genotypes such as EGFR mutation or
fusion gene (ALK translocation) are important factors in non-small cell lung cancer
(NSCLC) treatment. Pemetrexed (P)/cisplatin (C) is one of the standard treatments
Annals of Oncology
for advanced non-squamous (Nsq) NSCLC. However, the efficacy of the CP regimen
has not been well examined in Japanese Nsq NSCLC patients; furthermore, the
difference in efficacy between genotypes was not thoroughly examined. Therefore, the
present study was conducted to evaluate the efficacy of the CP regimen in Japanese
Nsq NSCLC patients, and to determine whether EGFR mutation and ALK
translocation impacted the treatment.
Methods: This study was conducted from May 2009 to December 2010. Patients
were eligible for this study if they had histologically or cytologically confirmed
recurrent or metastatic Nsq NSCLC previously untreated with chemotherapy, an
ECOG performance status of 0 or 1, life expectancy of more than 12 weeks, and
adequate organ function. Patients received C (75 mg/m2) plus P (500 mg/m2) on day
1 every 3 weeks. Of the 50 patients initially enrolled, 49 were evaluated, and 43
tumor samples were available for analysis. Most patients were male (80%), and 80%
of the patients had adenocarcinoma. The primary endpoint was the response rate
that was evaluated. according to RECIST. EGFR mutation was examined using
PCR-based methods, and the ALK fusion protein was examined using a highly
sensitive IHC method in the available tumor specimens.
Results: The objective response rate and disease control rate in all patients were
44.9% and 79.6%, respectively. The median progression-free survival was 4.4 months,
and the 1-year survival was 73.5%. Toxicities were mild; no new toxicity profile was
identified. Among the 43 samples, the following mutations were identified: 9 EGFRm
(21%), 5 ALK (12%), and 29 wild-type (67%). Objective response was observed in 6
(66.7%) EGFRm, 2 (40%) ALK (+), and 13 (44.8%) wild-type mutations.
Conclusion: Although the CP regimen demonstrates consistent efficacy in Japanese
Nsq NSCLC patients, EGFR mutation and ALK translocation may have impacted
this treatment.
Disclosure: All authors have declared no conflicts of interest.
1275P UPDATED SAFETY AND QUALITY OF LIFE (QOL) RESULTS
OF PARAMOUNT STUDY: MAINTENANCE PEMETREXED
(PEM) PLUS BEST SUPPORTIVE CARE (BSC) VS PLACEBO
(PBO) PLUS BSC IMMEDIATELY FOLLOWING INDUCTION
TREATMENT WITH PEM PLUS CISPLATIN (CP) FOR
ADVANCED NONSQUAMOUS NON-SMALL CELL LUNG
CANCER (NS-NSCLC)
J. Pujol 1 , L. Paz-Ares 2 , M. Dediu 3 , M. Thomas 4 , P. Bidoli 5 , J. Corral 2 ,
N. Chouaki 6 , C.M. Visseren-Grul 7 , A. Zimmermann 8 , C. Gridelli 9
1 Thoracic Oncologic Unit, Montpellier Academic Hospital, Hospital Arnaud de
Villeneuve, Montpellier, Montpellier, FRANCE, 2 Medical Oncology, Hospital
Universitario Virgen del Rocío, Seville, SPAIN, 3 Medical Oncology, Institute of
Oncology Bucharest, Fundeni Clinical Hospital Alexandru Treistoreanu,
Bucharest, ROMANIA, 4 Department of Thoracic Oncology, University of
Heidelberg, Thoraxklinik Heidelberg, GERMANY, 5 Medical Oncology, Azienda
Ospedaliera S. Gerardo U.O. Oncologia Medica, Monza, ITALY, 6 Medical
Department, Eli Lilly, Paris, FRANCE, 7 Oncology Europe, Eli Lilly, RA Houten,
NETHERLANDS, 8 Oncology, Eli Lilly and Company, Indianapolis, IN, UNITED
STATES OF AMERICA, 9 Medical Oncology, UO Oncologia Medica “S.G. Moscati
Hospital”, Avellino, ITALY
Objectives: The PARAMOUNT trial showed that continuation maintenance therapy
with pem after induction therapy with pem plus CP significantly reduced the risk of
disease progression (HR = 0.62) and death (HR = 0.78) in patients (pts) with
advanced NS-NSCLC. The purpose of this abstract is to present the updated safety
and patients’ QoL results from the continuation maintenance treatment of the
PARAMOUNT trial.
Methods: In this phase III, randomized, double-blind, PBO-controlled study, 939 pts
were treated with pem (500 mg/m 2 ) plus CP (75 mg/m 2 ) on day 1 of four 21-day
cycles. Patients (n = 539) who had not progressed and had an Eastern Cooperative
Oncology Group performance status (PS) of 0/1, were randomized (2:1; stratified for
PS, induction response, and disease stage) to maintenance pem (500 mg/m 2 ,day1)
plus BSC (n = 359) or PBO plus BSC (n = 180) until disease progression. All pts
received vitamin B 12, folic acid, and dexamethasone. All randomized pts were
qualified for the maintenance phase safety analyses, which included summaries of
the incidence of adverse events by maximum Common Terminology Criteria
Adverse Events, version 3, grade. All enrolled patients that had provided baseline and
at least 1 subsequent measurement for EuroQol 5-dimensional (EQ-5D) scale were
included in the analysis of patient-reported outcomes.
Results: Safety and the QoL analyses in the continuation maintenance therapy will
be presented.
Conclusions: The long-term and low-grade toxicities of continuation maintenance
therapy with pem will be discussed.
Disclosure: C.M. Visseren-Grul: Employed by and own stock in Eli Lilly and
Company. L. Paz-Ares: I have advisory board relationship and honararia to disclose
with Eli Lilly and Company, Bayer, Roche, Pfizer. I. M. Dediu: Advisory Board - Eli
Lilly and Company. M. Thomas: Advisory Board - Eli Lilly and Company Corporate
Sponsored Trial - Eli Lilly and Company. N. Chouaki: Employed by and own stock
in Eli Lilly and Company. A. Zimmermann: Employed by and own stock in Eli Lilly
and Company. J. Pujol: Advisory Board - Eli Lilly and Company. C. Gridelli:
ix418 | Abstracts Volume 23 | Supplement 9 | September 2012