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Annals of Oncology
secondary PRO endpoints. This advantage was generally consistent across analysis
method: time to worsening, best post-baseline score, and worst post-baseline score.
CS treated patients did report significantly better Chemotherapy Convenience and
Concerns scores, the difference was approximately one-half of a standard deviation
generally considered to be a meaningful difference.
Disclosure: All authors have declared no conflicts of interest.
696P A MULTI-CENTER PHASE II STUDY AND PREDICTIVE
BIOMARKER ANALYSIS OF COMBINED CETUXIMAB AND
MODIFIED FOLFIRI AS SECOND-LINE TREATMENT IN
PATIENTS WITH METASTATIC GASTRIC CANCER
L. Jin
Medical Oncolgy, Fudan University Cancer Center, Shanghai, CHINA
Background: This study was conducted to explore potential biomarkers for
predicting clinical outcome of cetuximab in combination with modified FOLFIRI
(mFOLFIRI) and to analyze safety of this regimen as a second-line treatment in
metastatic gastric cancer patients.
Methods: A total of 61 patients received an initial intravenous (IV) dose of
cetuximab (400 mg/m 2 ) and weekly doses (250 mg/m 2 ) thereafter. On day 2 of each
14-day period, patients received IV irinotecan (180 mg/m 2 ), leucovorin (200 mg/m 2 ),
and an IV bolus dose of 5-FU (400 mg/m 2 ) followed by a continuous infusion of
5-FU (2400 mg/m 2 ) for 46 hours. The primary endpoint was time-to-progression
(TTP).
Findings: The response rate (RR) was 33.3% among 54 evaluable patients. In the
intention-to-treat (ITT) analysis, median TTP was 4.6 months (95% confidential
interval [CI]: 3.6-5.6 months) and median overall survival (OS) was 8.6 months (95%
CI: 7.3-9.9 months). It was demonstrated that plasma vascular endothelial growth
factor (VEGF) levels could be a predictive factor for the treatment prognosis. In
patients with low (≤12.6 pg/ml) and high (>12.6 pg/ml) baseline plasma VEGF
levels, RR values were 55.0% and 5.3%, respectively (P = 0.001); median TTP values
were 6.9 months and 2.8 months, respectively (P = 0.0005); and median OS values
were 12 months and 5 months, respectively (P < 0.0001). None of these patients
exhibited KRAS, BRAF, or PIK3CA mutations.
Interpretation: Low baseline plasma VEGF levels were identified as a potential
predictive biomarker of prognosis. Combination therapy comprising cetuximab and
mFOLFIRI was well tolerated, which would be potentially used as a second-line
treatment for patients with advanced gastric cancer.
Funding: This study was supported by Fudan University Shanghai Cancer Center;
Merck KGaA Darmstadt, Germany, and National “Eleventh Five-year plan” new
drug discovery major projects of P. R. China.
Disclosure: All authors have declared no conflicts of interest.
697P FINAL ANALYSIS OF RANDOMIZED PHASE III STUDY
WJOG4007 COMPARING IRINOTECAN (CPT-11) WITH
WEEKLY PACLITAXEL (WPTX) IN ADVANCED GASTRIC
CANCER (AGC) REFRACTORY TO CHEMOTHERAPY (CT) OF
FLUOROPYRIMIDINE PLUS PLATINUM (FP)
T. Nishina 1 , S. Hironaka 2 , A. Tsuji 3 , K. Suzuki 4 , T. Otsuji 5 , T. Shibata 6 , S. Morita 7 ,
I. Okamoto 8 , N. Boku 9 , I. Hyodo 10
1 Gastrointestinal Oncology, National Hospital Organization Shikoku Cancer
Center, Matsuyama, JAPAN, 2 Clinical Trial Promotion Centre, Chiba Cancer
Center Hospital, Chiba, JAPAN, 3 Department of Medical Oncology, Kochi Health
Sciences Center, Kochi City, JAPAN, 4 Gastrointestinal Oncology, Kushiro City
General Hospital, Kushiro, JAPAN, 5 Gastrointestinal Oncology, Dongo Hospital,
Yamatotakata, JAPAN, 6 Gastrointestinal Oncology, Fujita Health University,
Toyoake, JAPAN, 7 Biostatistics and Epidemiology, Yokohama City University
Medical Center, Yokohama, JAPAN, 8 Medical Oncology, Kinki University School
of Medicine, Osakasayama, JAPAN, 9 Department of Clinical Oncology,
St. Marianna University School of Medicine, Kawasaki, JAPAN, 10 Gastrointestinal
Oncology, University of Tsukuba, Tsukuba, JAPAN
Background: We previously reported the primary results of WJOG4007 trial
comparing wPTX with CPT-11 for AGC refractory to combination CT of FP (Ueda
et al. ASCO 2012). This trial failed to demonstrate the superiority of CPT-11 to
wPTX in OS. Here, we report the results of subgroup analysis, cross-over effect and
patients’ general conditions at the time of discontinuation of protocol treatments.
Methods: The main inclusion criteria were; 1) refractory to combination CT of FP,
2) no prior CPT-11 or taxane, 3) no severe peritoneal metastasis. Pts with AGC
refractory to the 1st-line FP regimen were randomized 1:1 to either CPT-11 (150 mg/
m 2 , days1, 15, q4w) or wPTX (80 mg/m 2 , days 1, 8, 15, q4w). Cross-over treatment
between PTX and CPT-11 was recommended for the third line chemotherapy.
Results: Between Aug 2007 and Aug 2010, 223 pts were enrolled and 219 were
eligible; 108 pts were randomized to wPTX and 111 pts to CPT-11. Median OS for
wPTX and CPT-11 was 9.5 and 8.4 months (HR 1.13; 95% CI, 0.86-1.49; p = 0.38).
Subgroup analysis in OS revealed slightly favorable tendency of wPTX for almost all
factors such as age, gender, PS, prior gastrectomy, histological type, presence of
target lesion, peritoneal metastasis, number of metastatic sites. At the treatment
discontinuation, 85 pts (80%) with wPTX and 77 with CPT-11 (70%) maintained PS
0-1 (p = 0.12), and 2 (2%) and 13 pts (12%) were complicated with infection (p =
0.006), respectively. Thereafter, proportion of pts receiving third line CT was higher
in wPTX (89%) than CPT-11 (71%) (p = 0.04). As for the cross-over effect, among
86 pts (80%) in the wPTX group who received CPT-11 containing regimens in the
subsequent chemotherapy and 74 pts (67%) in the CPT-11 group who received
taxane containing regimens, survival curves were quite similar (10.1months, HR 0.96;
95%CI, 0.69-1.32).
Conclusions: In this trial, while patients in the wPTX group showed better condition
at the time of treatment discontinuation, a higher rate of subsequent CT and
cross-over CT, quite similar survival curves were observed in pts of both arms who
received cross-over treatments. It is speculated that the better condition at the end of
the second line chemotherapy resulting in higher proportion of the third line
chemotherapy might contribute to more favorable overall survival with wPTX than
CPT-11.
Disclosure: T. Nishina: Honoralia from Yakult Honsha, Daiichi Sankyo. I. Hyodo:
Honoralia from Yakult Honsha and Daiichi-Sankyo. All other authors have declared
no conflicts of interest.
698P PHASE II STUDY OF INTRAVENOUS AND INTRAPERITONEAL
PACLITAXEL COMBINED WITH S-1 FOR GASTRIC CANCER
WITH METASTASES TO THE DISTANT PERITONEUM
H. Ishigami 1 , J. Kitayama 2 , H. Yamaguchi 2 , S. Emoto 2 , T. Watanabe 2
1 Department of Outpatient Chemotherapy, The University of Tokyo, Tokyo,
JAPAN, 2 Department of Surgical Oncology, The University of Tokyo, Tokyo,
JAPAN
Background: Intraperitoneal (i.p.) chemotherapy is a promising treatment option for
gastric cancer with peritoneal metastasis. We previously carried out phase I and phase
II studies of intravenous (i.v.) and i.p. paclitaxel (PTX) combined with S-1, and
verified the safety and efficacy in gastric cancer with macroscopic peritoneal metastasis
and/or cancer cells on peritoneal cytology (Oncology 2009, Ann Oncol 2010). This
regimen was approved as an advanced medical treatment by the Ministry of Health,
Labour and Welfare of Japan, and further clinical studies were required for approval of
coverage by the Japanese Health Insurance System. Therefore, we carried out another
phase II study in gastric cancer patients with macroscopic peritoneal metastasis.
Patients and methods: Gastric cancer patients with macroscopic peritoneal
metastasis confirmed by staging laparoscopy were enrolled. PTX was administered i.
v. at 50 mg/m 2 and i.p. at 20 mg/m 2 on days 1 and 8. S-1 was administered orally
twice daily at 80 mg/m 2 /day for 14 consecutive days followed by 7 days rest. The
primary endpoint was the 1-year overall survival rate. Secondary endpoints were the
response rate, efficacy against malignant ascites and safety.
Results: Thirty-five patients were enrolled. All patients had several to numerous
metastases to the distant peritoneum. The median number of courses was 11 (range
2-29). The 1-year overall survival rate was 77% (95% CI, 63-91%). The overall response
rate was 71% in 7 patients with target lesions. Malignant ascites disappeared or decreased
in 6 of 9 (67%) patients with massive ascites. Cancer cells ceased to be detected by
peritoneal cytology in 28 of 29 (97%) patients. The incidences of grade 3/4 hematological
and non-hematological toxicities were 34% and 9%, respectively, all of which were
manageable and reversible. The frequent grade 3/4 toxicities included neutropenia (34%),
leukopenia (23%) and anemia (9%). There were no treatment-related deaths.
Conclusion: Combination chemotherapy of weekly i.v. and i.p. PTX combined with
S-1 is well tolerated and active in gastric cancer patients with macroscopic peritoneal
metastasis.
Disclosure: All authors have declared no conflicts of interest.
699P HER2 STATUS IN ADVANCED GASTRIC CARCINOMA
PATIENTS TREATED WITH TRASTUZUMAB
C. Gomez-Martin 1 , J.C. Plaza 2 , E. Del Valle 3 , F. Pons Valladares 4 ,P.
Jimenez Fonseca 5 , A. Salud 6 , A. Leon 7 , F. Rivera 8 , E. Garralda 1 , F. Lopez-Rios 2
1 Clinical Research Programme, Spanish National Cancer Research Center,
Madrid, SPAIN, 2 Laboratorio Dianas Terapeuticas, Hospital Universitario
Madrid-Norte Sanchinarro, Madrid, SPAIN, 3 Pathology Department, Hospital
Universitario Miguel Servet, Zaragoza, SPAIN, 4 Medical Oncology, Hospital del
Mar, Barcelona, SPAIN, 5 Medical Oncology, Hospital Universitario Central de
Asturias, Oviedo, SPAIN, 6 Medical Oncology, Hospital Universitario Arnau de
Vilanova, Lerida, SPAIN, 7 Medical Oncology, Fundacion Jimenez Diaz, Madrid,
SPAIN, 8 Medical Oncology, Hospital Universitario Marques de Valdecilla,
Santander, SPAIN
Background: Trastuzumab (T) added to standard chemotherapy increases overall
survival for HER2 positive advanced gastric carcinoma (AGC) patients. The approval
of T by the EMA in AGC was linked to the determination of the HER2-status by
immunohistochemistry (IHC), and hybridization was only permitted in the 2+
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds398 | ix233