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Annals of Oncology
reaction (HFSR) (71.9%), and the incidence at 4weeks, 8weeks,12weeks was
64.1%,45.3% and 37.5% respectively, showing a decline of HFSR incidence along
with the time of therapy . 21.9% of patients occurred ≥grade 2 other dermatologic
reactions other than HFSR, followed by diarrhea (26.2%), hypertension (15.4%) .
Dose interruptions due to toxicity happened in 19 patients (29.2%).
Conclusion: Sorafenib monotherapy has encouraging efficacy improving PFS and OS
with tolerable toxicity as second or third line treatment in patients with advanced
lung adenocarcinoma, who have failed prior chemotherapy and EGFR-TKI
treatment. Further randomized studies are needed to confirm the clinical benefit of
sorafenib in such patients.
Disclosure: All authors have declared no conflicts of interest.
1364TiP A RANDOMIZED, PHASE II, MULTICENTER,
DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF
ONARTUZUMAB (METMAB) WITH EITHER BEVACIZUMAB +
PLATINUM + PACLITAXEL OR PEMETREXED + PLATINUM
AS FIRST-LINE TREATMENT FOR PATIENTS (PTS) WITH
STAGE IIIB OR IV NON-SQUAMOUS NON-SMALL CELL
LUNG CANCER (NSCLC)
H. Wakelee 1 ,W.Yu 2 , K. Rittweger 3 , V.E. Paton 2
1 Thoracic Oncology, Stanford University Cancer Center, Stanford, CA, UNITED
STATES OF AMERICA, 2 Oncology, Genentech Inc, South San Francisco, CA,
UNITED STATES OF AMERICA, 3 Oncology, Hoffman-La Roche, Nutley, NJ,
UNITED STATES OF AMERICA
Background: Dysregulation of the HGF/Met pathway has been associated with
tumorigenesis in many malignancies, including NSCLC. Onartuzumab (MetMAb) is
a recombinant, humanized, monovalent monoclonal antibody directed against Met.
In a phase Ia/Ib study, onartuzumab (+/- bevacizumab) was well tolerated in pts with
advanced solid tumors (Moss et al. Ann Oncol 2010;21(Suppl. 8):Abstr. 504P). In a
phase II study of pts with previously treated NSCLC, onartuzumab + erlotinib was
associated with a significant benefit in PFS (HR 0.53; p = 0.04) and OS (HR 0.37; p =
0.002) compared with erlotinib alone in pts with Met IHC diagnostic-positive
(Met-positive) tumors (Spigel et al. J Clin Oncol 2011;29(Suppl.):Abstr. 7505). Pts
with Met-negative tumors who received onartuzumab + erlotinib reported worse
outcomes compared with erlotinib alone (PFS HR 1.82, p = 0.05; OS HR 1.78, p =
0.16). An interaction between onartuzumab and erlotinib could explain this outcome
and therefore may not be seen in this study with chemotherapy. The most
commonly reported adverse events associated with onartuzumab are peripheral
edema and fatigue. An early safety review is planned for this study.
Methods: In this study the treating physician will assign appropriate chemotherapy
for each pt (Cohort 1: bevacizumab + platinum + paclitaxel; Cohort 2: pemetrexed +
platinum). Eligible pts within cohorts will be stratified by Met IHC status (positive vs
negative) and randomized (1:1) to receive 4 cycles of chemotherapy + onartuzumab
or placebo. Thereafter, pts without disease progression may continue to receive
placebo or onartuzumab (+ cohort-assigned chemotherapy, without platinum or
paclitaxel) until disease progression, unacceptable toxicity, or death. The co-primary
endpoints are PFS in all pts and by Met status. Secondary endpoints include OS,
ORR, safety, and PK. Approximately 260 pts will be randomized until 130 pts with
Met-positive NSCLC are enrolled. This study is open for accrual; further details can
be found on ClinicalTrials.gov (NCT01496742).
Disclosure: H. Wakelee: Dr. Wakelee reports an uncompensated consultancy/
advisory relationship with Genentech-Roche. Dr Wakelee receives research funding
(through Stanford University) from Genentech-Roche. W. Yu: Dr Yu is a full-time
employee of Genentech, Inc. and minor stockholder of Hoffmann-La Roche, Inc. K.
Rittweger: Mrs Rittweger is a full-time employee of Hoffmann-La Roche, Inc. V.E.
Paton: Dr Paton is a full-time employee of Genentech, Inc. and minor stockholder of
Hoffmann-La Roche, Inc.
1365TiP A RANDOMIZED, PHASE II, MULTICENTER,
DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF
ONARTUZUMAB (METMAB) IN COMBINATION WITH
PACLITAXEL + CISPLATIN (OR CARBOPLATIN) AS
FIRST-LINE TREATMENT FOR PATIENTS (PTS) WITH
STAGE IIIB OR IV SQUAMOUS NON-SMALL CELL LUNG
CANCER (NSCLC)
F.R. Hirsch1 , D. Gandara2 , R. Govindan3 , V.E. Paton4 ,W.Yu4 1
Department of Medicine, University of Colorado Denver, Denver, CO, UNITED
STATES OF AMERICA, 2 Thoracic Oncolology Program, UC Davis Cancer Center,
Sacramento, CA, UNITED STATES OF AMERICA, 3 Oncology, Washington
University School of Medicine, St. Louis, MO, UNITED STATES OF AMERICA,
4
Oncology, Genentech Inc, South San Francisco, CA, UNITED STATES OF
AMERICA
Background: Dysregulation of the HGF/Met pathway has been associated with
tumorigenesis in many malignancies, including NSCLC. Onartuzumab (MetMAb) is
a recombinant, humanized, monovalent monoclonal antibody directed against Met.
By binding to the extracellular domain of Met, onartuzumab selectively blocks
ligand binding and subsequent activation by HGF. Current data support a strategy
of combining onartuzumab with numerous chemotherapies and targeted agents
(bevacizumab, erlotinib). In a phase Ia/Ib study, onartuzumab (monotherapy and in
combination with bevacizumab) was shown to be well tolerated in pts with
advanced solid tumors (Moss et al. Ann Oncol 2010;21(Suppl. 8):Abstr. 504P). A
phase II study of onartuzumab in combination with erlotinib in pts with previously
treated NSCLC reported a significant benefit in PFS (HR 0.53; p = 0.04) and OS
(HR 0.37; p = 0.002) in pts with Met-positive (Met IHC diagnostic positive) tumors
(Spigel et al. J Clin Oncol 2011;29 (Suppl.):Abstr. 7505). Pts with Met-negative
tumors who received onartuzumab + erlotinib reported worse outcomes compared
with erlotinib alone (PFS HR 1.82; p = 0.05; OS HR 1.78; p = 0.16). The most
commonly reported adverse events associated with onartuzumab are peripheral
edema and fatigue.
Methods: In this phase II study, pts with squamous NSCLC are randomized (1:1) to
receive 4 cycles of paclitaxel, cisplatin (or carboplatin) and either placebo or
onartuzumab. Pts without disease progression may continue to receive placebo or
onartuzumab as maintenance therapy until disease progression, unacceptable toxicity,
or death. The primary study endpoint is PFS in all pts. PFS by Met IHC diagnostic
status (Met positive vs Met negative) will also be analyzed. Secondary endpoints
include OS, ORR, safety, and PK. A minimum of 110 pts will be randomized to
achieve 55 pts with Met-positive squamous NSCLC. A maximum of 55 pts with
Met-negative squamous NSCLC will be enrolled. This study is open for accrual;
further details can be found on ClinicalTrials.gov (NCT01519804).
Disclosure: F.R. Hirsch: Advisory relationship: Genentech-Roche,
Boehringer-Ingelheim, Pfizer, Merck-Serono, Bristol-Myers Squibb. Research
funding (through University of Colorado): Imclone-Lilly, Celgene, Morphotek.
Board of Directors: IASLC. D. Gandara: Dr. Gandara reports a consultant/advisory
relationship with Genentech, Inc. He also receives research funding from
Genentech, Inc. R. Govindan: Dr. Govindan reports a consultant/advisory
relationship with Bristol-Myers Squibb, Boehringer-Ingelheim, Astra Zeneca, Pfizer,
Genentech, Inc. and GlaxoSmithKline. V.E. Paton: Dr Paton is a full-time employee
of Genentech, Inc. and minor stockholder of Hoffmann-La Roche, Inc. W. Yu: Dr
Yu is a full-time employee of Genentech, Inc. and minor stockholder of
Hoffmann-La Roche, Inc.
1366TiP PHASE II STUDY OF ERLOTINIB FOR PREVIOUSLY
TREATED NON-SMALL CELL LUNG CANCER PATIENTS
WITHOUT EPIDERMAL GROWTH FACTOR RECEPTOR
MUTATION: CENTRAL JAPAN LUNG STUDY GROUP
(CJLSG) 0903 TRIAL
M. Morise 1 , H. Taniguchi 2 , H. Saka 3 , J. Shindoh 4 , R. Suzuki 5 , E. Kojima 6 ,
T. Hase 1 , M. Kondo 1 , H. Saito 7 , Y. Hasegawa 1
1 Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya,
JAPAN, 2 Department of Respiratory Medicine and Allergy, Tosei General
Hospital, Seto, JAPAN, 3 Medical Oncology & Respiratory Medicine, National
Hospital Organization Nagoya Medical Center, Nagoya, JAPAN, 4 Respiratory
Medicine, Ogaki Municipal Hospital, Ogaki, JAPAN, 5 Respiratory Medicine,
Toyohashi Municipal Hospital, Toyohashi, JAPAN, 6 Respiratory Medicine, Komaki
Municipal Hospital, Komaki, JAPAN, 7 Respiratory Medicine, Aichi Cancer Center
Aichi Hospital, Okazaki, JAPAN
Background: Erlotinib has been shown moderate activity for previously treated
non-small cell lung cancer (NSCLC) patients with wild-type epidermal growth
factor receptor (EGFR). However, the sensitivity of methods for detection of EGFR
mutations can influence the efficacy of erlotinib. Moreover, it is controversial about
association between K-ras mutations and erlotinib resistance in EGFR wild-type
NSCLC. Here, we conducted a phase II study of erlotinib for previously treated
NSCLC patients without EGFR mutation screened by PNA-LNA PCR clamp
methods, which is known to be highly sensitive method for the detection of EGFR
mutations. Furthermore, we have planned exploratory reanalysis of EGFR mutation
status and screening of K-ras mutation status by the Scorpion Arms method which
is also highly sensitive method among patients whose samples are available for
analysis.
Patients and methods: Major eligibility criteria were advanced NSCLC with
EGFR-wild type (gene analysis by PNA-LNA PCR clamp method), previously treated
with one or two chemotherapy, and ECOG performance status (PS) of 0-2. Oral
erlotinib 150mg was given daily until progression or unacceptable toxicity. The
primary objective of the study was objective response rate. Secondary objectives were
tolerability, progression-free survival, overall survival, verification of the concordance
of EGFR mutation detection between the PNA-LNA PCR clamp method and
Scorpion ARMS method, and screening K-ras mutation status by Scorpion ARMS
methods. As of April 2012, enrollment of 55 patients has been completed. The study
is in progress and we are planning data cut-off for efficacy and safety analysis in
August 2012. (Unique trial Number; UMIN000002692)
Disclosure: H. Taniguchi: Hiroyuki Taniguchi has served as a member of advisory
boards for Boehringer-Ingelheim, Chugai-Pharma, Shionogi & Co. Ltd. H. Saito:
Hiroshi Saito received research funding from Chugai Pharmaceuticals. Y. Hasegawa:
Yoshinori Hasegawa received research funding from Chugai Pharmaceuticals. All
other authors have declared no conflicts of interest.
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds409 | ix445