Download the ESMO 2012 Abstract Book - Oxford Journals

Annals of Oncology
689P DISEASE PROGRESSION CLINICALLY JUDGED WITHOUT
CONFIRMATION BY IMAGE DIAGNOSIS IN A RANDOMIZED
PHASE III TRIAL OF ADVANCED GASTRIC CANCER
(JCOG9912)
H. Kawai 1 , N. Boku 2 , Y. Yamada 3 , N. Fuse 4 , H. Yasui 5 , A. Sawaki 6 , W. Koizumi 7 ,
J. Mizusawa 8 , K. Nakamura 8 , A. Takashima 8
1 Department of Endoscopy, Nagoya City West Medical Center, Nagoya, JAPAN,
2 Department of Clinical Oncology, St. Marianna University School of Medicine,
Kawasaki, JAPAN, 3 Medical Oncology, National Cancer Center Hospital, Tokyo,
JAPAN, 4 Division of Gastrointestinal Oncology and Digestive Endoscopy,
National Cancer Center Hospital East, Kashiwa, JAPAN, 5 Division of GI
Oncology, Shizuoka Cancer Center, Shizuoka, JAPAN, 6 Department of Clinical
Oncology, Nagoya Daini Red Cross Hospital, Nagoya, JAPAN, 7 Department of
Gastroenterology/gastrointestinal Oncology, Kitasato University Schoool of
Medicine, Sagamihara, JAPAN, 8 Japan Clinical Oncology Group Data Center,
Multi-Institutional Clinical Trial Support Center, National Cancer Center, Tokyo,
JAPAN
Background: In advanced gastric cancer (AGC), some type of progression such as
peritoneal metastasis are hardly detected by imaging, and progression was sometimes
judged clinically (C-PD) apart from imaging-determined progression (I-PD). Thus,
C-PD is regarded as a PFS event as well as I-PD in most cooperative group trials.
However, it has rarely been reported how often C-PD is observed in the clinical trials
of AGC. Objectives of this study are to evaluate the proportion of C-PD and to
compare the backgrounds and outcomes between C-PD and I-PD.
Methods: JCOG9912 is a large-scale randomized phase III trial comparing 5-FU
continuous infusion (5-FUci), irinotecan plus cisplatin and S-1 in AGC. Among all
randomized patients (n = 704), protocol treatments were terminated in 697 patients
at the final analysis, and the reasons for off-treatment were prospectively classified as
PD (n = 545), toxicities (n = 59), patient’s refusal (n = 73), death (n = 3) and others
(n = 17). We retrospectively categorized patients with PD to I-PD and C-PD by
reviewing the case report forms.
Results: The proportion of C-PD was only 4.4% (I-PD: n = 520, C-PD: n = 24,
unknown: n = 1) among those who terminated treatment due to PD. There were
some differences in patient backgrounds between I-PD and C-PD; age (median 63,
61.5 years old), diffuse type (51.0%, 70.8%), target lesion (+) (77.5%, 66.7%), sum of
longest diameter of target lesions (median 9.3cm, 7.9cm), treatment arm of 5-FUci
(36.2%, 45.8%), and second line chemotherapy (+) (83.1%, 70.8%). Median PFS in
I-PD and C-PD were 3.7 months and 3.8 months (HR = 0.94 [0.63-1.42] in
univariate analysis, HR = 0.93 [0.61-1.42] in multivariate analysis. Median OS in
I-PD and C-PD were 11.1 months and 9.3 months (HR = 1.19 [0.78-1.80] in
univariate analysis, HR = 1.25 [0.82-1.93] in multivariate analysis).
Conclusions: The proportion of C-PD was far less than expected. Although the PFS
in I-PD and C-PD were almost identical, there were some differences in patient
background and clinical courses after PD.
Disclosure: N. Fuse: I have research funding to disclose from Taiho Pharmaceutical
and Yakult Honsha. All other authors have declared no conflicts of interest.
690P A RANDOMIZED, CONTROLLED PHASE III TRIAL OF
DOCETAXEL, CISPLATIN AND FLUOROURACIL (DCF) VERSUS
CISPLATIN PLUS FLUOROURACIL (CF) AS FIRST-LINE
THERAPY IN CHINESE ADVANCED GASTRIC CANCER
L. Shen 1 ,R.Xu 2 , J. Wang 3 ,Y.Bai 4 , T. Liu 5 , S. Jiao 6 ,J.Xu 7 , Y. Liu 8 ,N.Fan 9
1 GI Department of Oncology, Peking University Cancer Hospital, Beijing, CHINA,
2 Department of Medical Oncology, Sun Yat-Sen University Cancer Center,
Guangzhou, CHINA, 3 Department of Oncology, Chinese Academy of Medical
Sciences, Cancer Institute and Hospital, Beijing, CHINA, 4 Department of
Oncology, Heilongjiang Cancer Hospital, Haerbin, CHINA, 5 Department of
Oncology, Zhongshan Hospital Fudan University, Shanghai, CHINA,
6 Department of Oncology, PLA General Hospital (301 Hospital), Beijing, CHINA,
7 Department of Oncology, 307 Hospital of PLA, Beijing, CHINA, 8 Department of
Oncology, The First Affiliated Hospital of China Medical University, Shenyang,
CHINA, 9 Department of Onclogy, Fujian Provincial Tumor Hospital, Fuzhou,
CHINA
Background: Gastric cancer is the second prevalent cancer in China accounting for
more than 200,000 deaths per year. Effective regimens are needed to improve the
outcome for gastric cancer patients. TAX 325 study has demonstrated OS benefit and
high toxicity of DCF regimen compared with CF in western population. Thus we
investigated the effect of modified DCF (mDCF) regimen in Chinese patients with
advanced gastric cancer in this prospective, multicenter, open-label, randomized and
parallel-controlled phase III study.
Methods: Eligible no prior palliative chemotherapy, advanced gastric cancer patients
were randomized to either mDCF (Docetaxel 60mg/m 2 1-hour intravenous infusion
(IV) and cisplatin 60mg/m 2 1-3-hour IV on day 1, followed by fluorouracil 600mg/
m 2 /d continuous IV for 5 days, every 3 weeks) or modified CF (mCF) (cisplatin
75mg/m 2 1-3-hour IV on day 1, followed by fluorouracil 600mg/m 2 /d continuous IV
for 5 days, every 3 weeks). Treatment continued until disease progression,
unacceptable toxicity, death, or consent withdrawal. The primary end point was
progression-free survival (PFS).
Results: Between Nov 2008 and Dec 2010, a total of 241 patients were randomized,
234 patients were treated and analyzed (mDCF = 119, mCF = 115) PFS was
prolonged with mDCF vs mCF significantly (HR, 0.63; 95% CI, 0.48 to 0.85; P =
0.0018; median PFS, 7.2 months vs.4.9 months), the trend of OS improvement was
seen (HR, 0.78; 95% CI, 0.58 to 1.05; P = 0.099; median OS 10.2 months vs. 8.5
months), Overall best response rate (ORR) was improved significantly with mDCF vs
mCF (58% vs 39%, P = 0.0244). Treatment related grade 3/4 AEs occurred in 75.6%
(DCF) vs 33.0% (CF), P < 0.0001. The most frequent 3/4 AEs included neutropenia
(60.5% vs 8.7%), diarrhea (12.6% vs 0), vomiting (7.6% vs 11.3%) and febrile
neutropenia (12.6% vs 0).
Conclusion: mDCF regimen significantly improved PFS and ORR. The safety profile
was consistent with previous report. mDCF should be considered as an option for
untreated Chinese advanced gastric cancer patients. This study was funded by Sanofi,
ClinicalTrials.gov identifier: NCT00811447.
Disclosure: All authors have declared no conflicts of interest.
691P EVEROLIMUS (EVE) EXPOSURE IN PATIENTS (PTS) WITH
PREVIOUSLY TREATED ADVANCED GASTRIC CANCER (AGC)
S. Al-Batran 1 , N. Tebbutt 2 ,J.Xu 3 , G. Luppi 4 , H. Smith 5 , C. Costantini 6 ,
W. Cheung 5 , S. Rizvi 7 , T. Sahmoud 8 , L. Shen 9
1 Medizinische Klinik Ii für Hämatologie und Onkologie, Institut für klinische
Forschung (IKF) am Krankenhaus Nordwest - UCT, Universitäres Centrum für
Tumorerkrankungen Frankfurt, Frankfurt, GERMANY, 2 Medical Oncology, Austin
Hospital, Heidelberg, AUSTRALIA, 3 Gastrointestinal Oncology, 307 Hospital of
PLA, Beijing, CHINA, 4 Oncology, Azienda-Ospedaliero Universitaria di Modena,
Modena, ITALY, 5 Oncology, Novartis Pharmaceuticals Corporation, Florham
Park, NJ, UNITED STATES OF AMERICA, 6 Oncology, Novartis Pharma AG,
Basel, SWITZERLAND, 7 Oncology Clinical Research and Development, Novartis
Pharmaceuticals, Florham Park, NJ, UNITED STATES OF AMERICA, 8 2W274,
Novartis Pharmaceuticals, Florham Park, NJ, UNITED STATES OF AMERICA,
9 Internal Medicine, Peking University Cancer Hospital, Beijing, CHINA
Background: In GRANITE 1, EVE did not significantly improve overall survival
(OS) over best supportive care (BSC) in previously treated AGC (median OS 5.4 mo
with EVE vs 4.3 mo with BSC; HR, 0.90; P = .1244). Median progression-free survival
(PFS) was 1.7 mo with EVE vs 1.4 mo with BSC (HR, 0.66; P < .0001). This analysis
examined EVE exposure and its relationship with efficacy and safety.
Methods: Pts with confirmed AGC who progressed after 1 or 2 chemotherapy lines
were randomized 2:1 to EVE 10 mg/d + BSC or placebo + BSC. Primary endpoint was
OS. EVE C min and C max were determined in whole blood from samples collected
predose and 1 and 2 h postdose on day 1 of wk 5 using liquid chromatography/mass
spectrometry (lower limit of quantification 0.3 ng/mL). Cox models adjusted for
region (Asia/rest of world [ROW]) and gastrectomy (yes/no) were used to explore
relationships between PFS and time-normalized (TN) EVE Cmin. A linear
mixed-effects model was used to explore the relationship between change from
baseline in target lesion size and TN C min. Kaplan-Meier curves for select adverse
events (AEs) by TN C min categories were prepared.
Results: 656 pts were enrolled from Jul 2009 to Dec 2010 and received EVE (n =
439) or placebo (n = 217). Median age was 62 y, 74% were men, 55% were from Asia,
and 50% had previous gastrectomy. Mean ± SD Cmin and Cmax were 16.1 ± 10.8 ng/
mL and 72.8 ± 36.5 ng/mL in pts receiving EVE 10 mg/d at sampling. EVE Cmin and
C max were similar in pts from Asia and ROW and in pts with and without
gastrectomy. No significant relationship between TN C min and PFS was observed
(HR, 0.83; 95% CI, 0.65-1.06). A 2.72-fold increase in TN C min corresponded to a
significant 7.6% reduction from baseline in target lesion volume. No differences in
noninfectious pneumonitis, stomatitis/oral mucositis, or infection/infestation risk in
pts with TN Cmin