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3523Background: APOLLON is an open-label, single-arm phase I/II study investigating the efficacy and safety of panitumumab (Pmab) in combination with TAS-102 (trifluridine/tipiracil) in pts with RA...

4029Background: WJOG7112G study, comparing paclitaxel plus trastuzumab (PT; n = 44) with paclitaxel alone (P; n = 45), did not demonstrate survival benefit of trastuzumab continuation beyond progre...

10094Background: KSCC1402/HGCSG1402 is a phase II, randomized, double-blind, placebo (PLC)-controlled study evaluating the prophylactic effects of oral dexamethasone (DEX) on regorafenib-related fa...

699 Background: Plasma levels of VEGF-A short isoforms (VEGF-A110 and -A121) measured by immunological multiparametric chip technique (IMPACT) were reported to be associated with clinical benefits from bevacizumab (BV) in advanced gastric and pancreatic cancer but not in metastatic colorectal cancer (mCRC). Negative results in mCRC studies might be caused by different sample handling: citrate instead of EDTA and repetition of freeze/thaw. Methods: Blood samples were collected in EDTA before the first-line treatment with BV+mFOLFOX6 or +XELOX for mCRC. Plasma samples were analyzed at Roche Diagnostics Ltd. (Penzberg, Germany) using IMPACT-2 (Roche proprietary multiplex enzyme-linked immunosorbent assay platform). A median value of pVEGF-A was used as a cut-off point to categorize patients (pts) into the low and high pVEGF-A groups. Progression free survival (PFS) and overall survival (OS) between the low and high pVEGF-A groups were compared, using Cox proportional hazards model. We hypothesized that BV-containing treatment extend shorter PFS of pts with high pVEGF-A to that with low pVEGF-A, and estimated a threshold hazard ratio (HR) between them as below 1.15. Results: Among 102 pts enrolled between January 2014 and April 2015, 100 (53 BV+mFOLFOX6 and 47 BV+XELOX) were eligible. Median PFS was 11.4 months [95% CI, 9.5-13.0] and response rate was 64.6 % [range, 53.3-74.9]. pVEGF-A was measured in 97 pts and the median value was 36.8 pg/ml [range, 6.5- 262.2]. The hazard ratios of PFS and OS between the high and low pVEGF-A groups were 1.23 [95%CI, 0.76-1.97, p = 0.40] and 2.47 [95%CI, 1.14-5.36, p = 0.02], respectively. Conclusions: mCRC pts with high pVEGF-A showed shorter PFS than those with low pVEGF-A beyond the predefined threshold (HR 1.15) in BV-containing chemotherapy, suggesting that pVEGF-A could not be a predictive marker for BV efficacy. Clinical trial information: UMIN000012442.

670 Background: Bevacizumab (BV)-containing chemotherapy has been established as the standard first-line treatment for metastatic colorectal cancer (mCRC). However, no biomarkers have been established to predict the clinical benefit of BV for patients (pts) with mCRC. Methods: Blood samples were collected in EDTA before the first-line treatment with BV+mFOLFOX6 or +XELOX for mCRC. Plasma samples were analyzed at Roche Diagnostics Ltd. (Penzberg, Germany) using IMPACT-2 (Roche proprietary multiplex enzyme-linked immunosorbent assay platform). Median values of pICAM-1 and pIL-8 were used as cut-off points to categorize pts into the low and high groups. Progression free survival (PFS) and overall survival (OS) were compared between two groups, using Cox proportional hazards model. Results: Among 102 pts enrolled between January 2014 and April 2015, 100 (53 BV+mFOLFOX6 and 47 BV+XELOX) were eligible. Median PFS was 11.4 months [95% CI, 9.5-13.0]. Response rate was 64.6 % [53.3-74.9]. pICAM-1 and pIL-8 were measured in 99 pts and the median values were 190.0 ng/ml [range, 58.0- 1080.1] and 311.5 pg/ml [range, 83.2-4541.4], respectively. The hazard ratios of PFS and OS between the high and low pICAM-1 groups were 2.08 [95%CI, 1.28-3.40, p = 0.003] and 2.04 [0.92-4.50, p = 0.079], respectively. The hazard ratios of PFS and OS between the high and low pIL-8 groups were 1.63 [95%CI, 1.00-2.65, p = 0.048] and 3.42[1.57-7.44, p = 0.002], respectively. Conclusions: High pICAM-1 and pIL-8 were associated with short PFS and OS of mCRC pts treated with BV-containing chemotherapy, suggesting that pICAM-1 and pIL-8 could be predictive markers for prognosis of mCRC treated with BV. Clinical trial information: UMIN000012442.

624 Background: A randomized phase II WJOG6510G study demonstrated non-inferiority of panitumumab (Pmab) plus irinotecan (IRI) to cetuximab (Cmab) plus IRI in terms of progression-free survival (PFS) in wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC). Here, we performed exploratory analyses of updated survival data using KRAS exon 2 and RAS/BRAF statuses. Methods: In this trial, patients with WT KRAS exon 2 mCRC who progressed after failure of fluoropyrimidine, IRI, and oxaliplatin were randomized to receive Pmab or Cmab in combination with IRI. An independent central laboratory performed RAS/BRAF testing using a PCR-reverse sequence specific oligonucleotide method which can detect 48 types of KRAS/NRAS and 34 types of BRAF mutations. Results: In the ITT population, patient characteristics included the following (Pmab/Cmab): number 61/59; male 69%/63%; median age 64 y/64 y; ECOG PS 0 62%/54%; left-sided primary tumor 85%/88%; multiple sites of metastases 51%/66%. At the time of updated analysis, 113 (94%) and 117 (98%) out of 120 patients had OS and PFS events, respectively. Median PFS was 5.42 months in the Pmab arm and 4.27 months in the Cmab arm (HR 0.674, unstratified log-rank p = 0.035). Median overall survival (OS) was 14.85 months in the Pmab arm and 11.53 months in the Cmab arm (HR 0.675, p = 0.037). In 83 patients, RAS/BRAF tests revealed 19 patients (23%) with RAS and 4 patients (5%) with BRAF mutations (two with V600E, two with non-V600E). Patients with RAS and BRAF mutations did not respond to the treatments. In the RAS WT population, a better PFS trend was observed for Pmab treatment (median 6.06 months vs. 5.26 months, HR 0.629, p = 0.08); however, OS was similar in both arms (median 14.85 months vs. 11.26 months, HR 0.818, p = 0.449). Conclusions: In this analysis, a modest survival benefit was found to be associated with Pmab plus IRI compared to Cmab plus IRI in WT KRAS exon2 mCRC, which warrants further evaluation in the WT RAS population. The number of analytic cases of RAS/BRAF status will be updated in the presentation. Clinical trial information: UMIN000006643.

Salvage-line regorafenib monotherapy exhibited a marked survival benefit for metastatic colorectal cancer (mCRC). However, the toxicity of this regimen has resulted in the clinical use of a reduced dose of regorafenib.Thirty-two Japanese mCRC patients (median age=61 years) who had been treated with regorafenib were retrospectively examined.Best objective response rate was 0% and stable disease (SD) was 31%. Median progression-free survival was 81 days and median overall survival was 233 days. Adverse events of any grade were observed in all patients: 17 (53%) patients suffered grade 3 or 4 adverse events including fatigue (13%), anorexia (13%), hand-foot skin reaction (22%) and elevations of alanine aminotransferase/aspartate aminotransferase (19%/16%). One patient with grade 5 liver dysfunction was identified (3%). Twenty-nine (91%) patients required treatment dose reduction or a delay in treatment. The relative dose intensity was 59%. Regorafenib treatments were terminated because of disease progression (59%) or adverse events (34%).Despite a decrease in the intensity of regorafenib treatment, because of severe adverse events, a fairly favorable efficacy was achieved in Japanese patients.

4059 Background: A combination of S-1 and cisplatin (SP) has been the standard regimen for advanced gastric cancer (AGC) in East Asia. The combination of S-1 and oxaliplatin (SOX100) was demonstrated to be non-inferior to SP in the randomized phase III study. The ToGA study demonstrated that trastuzumab (T-mab) combination therapies with cisplatin and fluoropyrimidines improved the overall survival of patients with HER2-positive AGC. This multicenter study is the first phase II trial to assess the efficacy and safety of T-mab in combination with S-1 and oxaliplatin (HER-SOX130) in HER2-positive AGC. Methods: Patients with HER2-positive AGC or recurrent gastric cancer defined to be IHC 3+ or IHC 2+/FISH positive received 80 mg/m2 S-1 per day orally on days 1–14, 130 mg/m2 oxaliplatin intravenously on day 1, and T-mab (8-mg/kg loading dose and 6 mg/kg thereafter) intravenously on day 1 of a 21-day cycle until one of the criteria for withdrawal of the study treatment occurred. The primary end-point was the response rate (RR). Adverse events were recorded based on the NCI-CTCAE Vers.4.0. The threshold response rate was defined as 50%, and the expected rate was set at 70%, with an 80% power and a 1-sided alpha value of 0.05. The calculated sample size was 37 patients. Results: For this study, 42 patients (median age, 66 years) were enrolled from June 2015 to May 2016. Three patients were excluded owing to ineligibility. Efficacy and safety analyses were conducted in the full analysis set of 39 patients. The proportion of patients with IHC 3+ was 87%. The confirmed RR assessed by the independent review committee was 82.1(32/39) % (95% confidence interval [CI]: 67.3–91.0), and the disease control rate was 87.2(34/39) % (95% CI: 73.3–94.4). The incidence rates of grade 3 or 4 adverse events were as follows: neutropenia, 12.8%; thrombocytopenia, 17.9%; anemia, 10.3%; sensory neuropathy, 5.1%; anorexia, 17.9%; diarrhea, 7.7%; and teary eyes, 2.6%. Conclusions: HER-SOX130 demonstrated encouraging efficacy with a favorable safety profile. The survival benefit of this regimen needs to be validated by conducting further follow-up of patients. Clinical trial information: 000017552.

3540 Background: It is unclear which drug of REG or TAS-102 should be used earlier for the patients with metastatic colorectal cancer (mCRC) who have access to both drugs. This study investigated the comparison of the efficacy between REG and TAS-102 in patients with refractory to standard chemotherapies. Methods: The clinical data of patients who were treated with REG or TAS-102 among these drugs naive mCRC patients between Jun 2014 and Sep 2015 were retrospectively delivered from 24 institutions of Japanese Society for Cancer of the Colon and Rectum (JSCCR). The primary endpoint was overall survival (OS). Propensity score (PS) was calculated with a logistic regression, in which using baseline parameters were included. Two methods, adjusted and matched analysis, to take propensity score were used. The clinical outcomes were evaluated with Kaplan-Meier method and Cox models based on PS adjustment and matching. Results: Total of 589 patients were enrolled and 550 patients (223 patients in the REG group and 327 patients in the TAS-102 group) met criteria for inclusion in the analysis. The results from PS adjusted analyses showed that OS was similar between the two groups (HR of TAS-102 to REG, 0.96; 95% confidence interval, 0.78–1.18). There were also no statistically significant differences between two groups for progression-free survival (HR 0.94) and time to ECOG Performance status≥2 (HR 1.00), expect for time to treatment failure (HR 0.81; P = 0.025). In the subgroup analysis, REG showed favorable survival compared with TAS-102 in the age of < 65 years patients and unfavorable survival in ≥65 years patients (P for interaction = 0.012). In the PS matched sample (174 patients in each group), the clinical outcomes were similar to the results of the PS adjusted analysis. Conclusions: Although REG and TAS-102 showed a similar efficacy in mCRC patients with refractory to standard chemotherapies, the choice of the drug by age might affect the survival. Supported by JSCCR. Clinical trial information: UMIN000020416

661 Background: Continuation of CPT-11 in combination with Cmab after CPT-11 failure has a survival benefit over Cmab alone. However, it is not clear whether CPT-11 with Pmab shows similar benefits. Methods: Pts with KRAS WT mCRC previously treated with FU-, L-OHP-, and CPT-11- based chemotherapies were randomized 1:1 to either Cmab + CPT-11(Cmab arm), or Pmab + CPT-11(Pmab arm). Primary objective was progression free survival (PFS), with an expected hazard ratio (HR) of 1.0 with non-inferiority margin of 1.3 (80% CI) using cox proportional hazards model. Median PFS with both arms were assumed to be 6.0 months. Secondary objectives were overall survival (OS), response rate (RR), disease control rate (DCR), and safety. Results: From December 2011 to September 2014, 121 pts were enrolled from 31 sites in Japan. Because 1 patient declined before treatment, totally, 120 (Cmab arm: 59, Pmab arm 61) pts were eligible for efficacy analysis. Baseline characteristics were well balanced between the two arms. 116 pts (96.7 %) were previously treated with bevacizumab. Efficacy results are shown in the table. The common grade 3 or 4 adverse events in Cmab/Pmab arm were leukopenia 19.0/3.3%, neutropenia 27.6/8.3%, hypomagnesaemia 6.9/16.7%, and rash 5.2/13.3 %, respectively. Conclusions: Non-inferiority of Pmab to Cmab in combination with CPT-11 was suggested for patients with KRAS WT mCRC previously treated with FU-, L-OHP-, and CPT-11- based chemotherapies, associated with favorable PFS and OS. Clinical trial information: UMIN000006643. [Table: see text]

93 Background: The concept of using trastuzumab (Tmab) beyond progression (TBP) is currently accepted in HER2-positive metastatic breast cancer. However, TBP has never been investigated in cases of HER2-positive advanced gastric or gastro-esophageal junction (G/GEJ) cancer. KSCC1105 is an observational cohort study designed to investigate the clinical outcomes associated with Tmab combined with chemotherapy including TBP strategy in part, as used in clinical practice, for the treatment of advanced G/GEJ cancer. Methods: Patients (pts) with advanced HER2-positive G/GEJ cancer receiving Tmab between March 2011 and January 2014 were enrolled. Data regarding the baseline characteristics before Tmab plus chemotherapy, pre-specified Tmab-related adverse events, and effectiveness were collected retrospectively. Treatment outcomes were estimated using Kaplan-Meier method and compared using log-rank test. Results: Of 181 enrolled pts, 179 were eligible for analysis and 123 received Tmab as first-line chemotherapy. Among the 123 pts, 85 were able to undergo second-line therapy with or without Tmab. We divided these 85 pts into those treated with Tmab (TBP group, n = 59; 69%) and those treated without Tmab (non-TBP group, n = 26; 31%) in the second-line chemotherapy. The baseline characteristics were similar between the two groups. The median OS was significantly longer in the TBP group (12.8 months; 95% CI 9.0–16.5 months) than in the non-TBP group (7.9 months; 95% CI 5.1–10.7 months) (hazard ratio = 0.50; 95% CI 0.29–0.84; p = 0.010). Infusion-related events were more frequent in the TBP group (20.3%) than in the non-TBP group (11.5%); however, no significant difference was observed. No cardiac event-related death was observed in either group. Conclusions: TBP may be associated with a better prognosis, without severe toxicity. A randomized controlled trial to assess TBP (T-ACT trial; WJOG7112G) is currently being undertaken by the West Japan Oncology Group.

681 Background: Several studies have shown that capecitabine plus irinotecan (XELIRI) has promising efficacy and safety in patients with metastatic colorectal cancer. AXEPT is a non-inferiority, phase III comparison of XELIRI with or without bevacizumab vs 5-fluorouracil/folinic acid plus irinotecan (FOLFIRI) with or without bevacizumab as second-line therapy in patients with metastatic colorectal cancer. Methods: We undertook an open-label, non-inferiority, randomized phase III trial in South Korea, China and Japan. Patients were randomized 1:1 to XELIRI (irinotecan 200 mg/m2 on day 1 plus capecitabine 800 mg/m2 twice daily for 2 weeks in a 3-week cycle) with or without bevacizumab 7.5 mg/kg or FOLFIRI with or without bevacizumab. The primary endpoint was overall survival. Results: From December 2013 to August 2015, 650 patients were enrolled and 625 (311 in FOLFIRI and 314 in XELIRI) were included to safety analysis at the cutoff dates on August 31, 2016. Patient baseline characteristics including KRAS status and UGT1A1 gene polymorphism were similar between the two treatment arms. Prior chemotherapy with oxaliplatin was given to 97.4% in both arms. The overall incidence of grade 3-4 toxicity was 73% in FOLFIRI arm and 53.2% in XELIRI arm. Whereas FOLFIRI was associated with more grade 3-4 neutropenia (43.7% vs 16.2%), leucopenia (13.5% vs 7.3%) and all grades anemia (80.4% vs 69.4%) than XELIRI, XELIRI was associated with more all grades hand-foot syndrome (34.1% vs 14.8%) and grade 3-4 diarrhea (7.0% vs 3.2%). There was no significant difference in febrile neutropenia (4.2% in FOLFIRI and 2.9% in XELIRI). The addition of bevacizumab did not alter safety profiles between XELIRI and FOLFIRI. There was a treatment-related death in FOLFIRI arm (0.3%). Conclusions: Both FOLFIRI and XELIRI were safe and well tolerated, though there were differences in the rates and toxicity profiles at which adverse events occur. Clinical trial information: NCT01996306. UMIN000012263.

TPS218 Background: Trastuzumab (Tmab) is a key drug for HER2 positive breast and gastric or gastro-esophageal junction (G/GEJ) cancer. While use of Tmab beyond progression (TBP) showed a benefit in HER2-positive metastatic breast cancer, clinical significance of TBP for HER2-positive G/GEJ cancer has not been clarified. Objective:This study compares the efficacy of paclitaxel (PTX) + Tmab with PTX alone in patients with unresectable or metastatic HER2-positive G/GEJ cancer who failed first-line chemotherapy with Tmab + fluoropyrimidine + platinum. Methods: Enrolled patients will be randomized to receive PTX (80 mg/m2, on day 1, 8 15, every 4 weeks) + Tmab (8 mg/kg loading dose and 6 mg/kg thereafter, on day 1, every 3 weeks) or PTX alone. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, time to treatment failure, response rate, disease control rate, safety, and translational biomarker research. A total of 69 events are required to achieve 80% power for one-sided log rank test with 10% significance level, expecting the median PFS of the PTX and the PTX + Tmab arms will be 3 and 5 months. In consideration of patient with censoring and dropout, the planned sample size is totally 90 patients. Major eligibility criteria are: HER2-positive advanced G/GEJ adenocarcinoma; refractory to first-line chemotherapy with fluoropyrimidine, platinum, and Tmab (at least three doses); within 6 weeks after last Tmab administration; no prior therapy with taxane or anti-HER2 drugs except Tmab; ECOG PS 0-2; adequate organ function; left ventricular ejection fraction ≥ 50%. Tumor tissue, blood serum, and circulating tumor DNA are collected before the study treatment for biomarker analyses to explore the predictive marker of the TBP strategy. As of September 2016, 89 patients were randomized. Clinical trial information: 000009297.

Malignant peritoneal mesothelioma (PM) is an extremely rare disease. Pemetrexed and platinum have been used for advanced PM following malignant pleural mesothelioma (PLM). Because PM differs considerably from PLM in clinical features, the efficacy and safety of these therapies have yet to be established.Six Japanese patients with PM who had been treated with pemetrexed-based chemotherapy in four Institutions were retrospectively identified. Treatment response, progression-free survival, and overall survival were examined. Toxicities of therapy were also evaluated.Three patients with mild ascites achieved clinical benefits (one with partial response and two with stable disease). Treatments with reduced cisplatin or carboplatin for patients with massive ascites were safely performed. Median PFS and OS were 7.2 and 13.1 months, respectively. Grade 3 hematological toxicities appeared in two patients with massive ascites.Selection of chemotherapy based on the patient's condition, such as ascites, might be important for advanced PM.

10127Background: Regorafenib (REG) is an oral multikinase inhibitor with survival benefit in salvage line therapy for metastatic colorectal cancer (mCRC); fatigue and malaise which are common adver...

AZD7762, a potent Chk1/Chk2 inhibitor, has shown chemosensitizing activity with gemcitabine in xenograft models.This open-label, Phase I, dose-escalation study evaluated the safety, pharmacokinetics (PK) and preliminary efficacy (RECIST) of AZD7762 alone and in combination with gemcitabine in Japanese patients with advanced solid tumours (NCT00937664). Patients received intravenous AZD7762 alone on days 1 and 8 of a 14-day cycle (cycle 0), followed by AZD7762 plus gemcitabine 1,000 mg/m(2) on days 1 and 8 of 22-day cycles, in ascending AZD7762 dose cohorts.Twenty patients received AZD7762 at doses of 6 mg (n = 3), 9 mg (n = 3), 21 mg (n = 6) and 30 mg (n = 8). Dose-limiting toxicities occurred in 2/6 evaluable patients in the 30-mg cohort: one, CTCAE grade 3 elevated troponin T (cycle 0: AZD7762 monotherapy); one, neutropenia, thrombocytopenia, and elevated aspartate aminotransferase and alanine aminotransferase (cycle 1: combination therapy). The 30 mg dose was therefore regarded as non-tolerable. The most common adverse events (AEs) in cycle 0 (AZD7762 monotherapy) were bradycardia (50 %), hypertension (25 %) and fatigue (15 %). Overall, the most common AEs were bradycardia (55 %), neutropenia (45 %) and hypertension, fatigue and rash (30 % each). Grade ≥3 AEs were reported in 11 patients, the most common being neutropenia (45 %) and leukopenia (25 %). AZD7762 exposure increased approximately linearly. Gemcitabine did not appear to affect AZD7762 PK. There were no objective responses; five patients (all lung cancer) had stable disease.The maximum tolerated dose of AZD7762 in combination with gemcitabine, 1,000 mg/m(2) was determined as 21 mg in Japanese patients.

Using the recommended doses obtained from our previous phase 1 trial of a modified Saltz chemotherapy regimen for metastatic colorectal cancer (weekly irinotecan and bolus 5-fluorouracil/l-leucovorin for 3 weeks every 28 days), we performed the present phase 2 trial to evaluate efficacy and toxicity.A total of 29 patients with metastatic colorectal cancer were included. Our modified Saltz regimen was administered. The primary endpoint was overall response rate.Of the 29 patients, 11 had previous chemotherapy. A partial response occurred in 11 patients, stable disease in 16 patients, and progressive disease in two patients. Disease control rate was 93.1%. Response rates with and without previous treatment were 18.2% and 50%, respectively. Median progression-free survival was 17.3 months. The main hematologic toxicities were leukopenia (22.6%) and neutropenia (45.2%). No treatment-related deaths occurred.Our modified Saltz regimen exhibited sufficient efficacy, feasibility, and manageable toxicity as a therapeutic option for selected colorectal cancer patients.

To define the most effective combination schedule of gemcitabine and oxaliplatin (L-OHP), we investigated the in-vitro interaction between these drugs in a panel of four human gallbladder adenocarcinoma cell lines (HAG-1, GB-d1, NOZ, and G-415). Cytotoxic activity was determined by the WST-1 assay. Different schedules of the two drugs were compared and evaluated for synergism, additivity, or antagonism with a quantitative method based on the median-effect principle of Chou and Talalay. Cell cycle perturbation and apoptosis were evaluated by flow cytometry. Simultaneous and sequential treatments of gemcitabine followed by L-OHP exhibited synergistic effects in all four cell lines, whereas the reverse sequence largely showed an antagonism. Gemcitabine exclusively arrested cells at the G 0 /G 1 phase, and L-OHP at the G 2 /M phase, as measured by flow cytometric analyses. Apoptosis was most prominent when cells were treated simultaneously or in a sequence gemcitabine followed by L-OHP, producing apoptosis in treated cells (27-30%). In contrast, the reverse sequence yielded only 6-7% induction of apoptosis, the rate being not significantly different from those induced by each drug singly. Moreover, this sequence dependence was further confirmed by the experiment, which compared the number of HAG-1 cells 7 days after these combination schedules. These findings suggest that the interaction of gemcitabine and L-OHP is highly schedule dependent, with the most efficacious interaction observed in either simultaneous combination or in a sequence combination of gemcitabine followed by L-OHP.

9598 Background: Superiority of palonosetron to granisetron is uncertain, for patients with breast cancer receiving both steroid and NK1 inhibitor against CINV caused by AC regimen. Methods: We con...

757 Background: Progression free survival (PFS) has been recognized as a surrogate outcome in the therapy for metastatic or recurrent colorectal cancer (mCRC). As molecular targeted therapies have become to be widely used, new surrogate outcome such as early tumor shrinkage (ETS; the relative change in the sum of longest diameters of target lesions at week 8 compared to baseline) and deepness of response (DpR; the relative change in the sum of longest diameters of target lesions at the nadir compared to baseline) are proposed. However, their validity has not been fully proven. We conducted to develop a new prognosis predictive formula consisting of the three factors, DpR, ETS and PFS, in the first-line chemotherapy of mCRC. Methods: We retrospectively evaluated mCRC patients who started any chemotherapy from 2005 to 2010. Estimated ETS (eETS), instead of ETS, was defined as the estimated relative change of target lesions at week 8 calculated from first image assessment. DpR was defined as above. Predictive formulae of prognosis were examined by single and multiple regression analysis. Results: 63 patients were enrolled. KRAS status were as follows; wild type; 33, mutant; 17, unknown; 13. Chemotherapies were performed as follows; oxaliplatin-based plus bevacizumab; 34, irinotecan-based plus bevacizumab; 6, oxaliplatin-based plus anti-EGFR antibody; 2, oxaliplatin-based; 17, irinotecan-based; 4. Median of DpR, eETS, PFS and overall survival (OS) were 26.5%, 15.4%, 236 days and 571 days, respectively. PFS showed a correlation with OS (r2= 0.434), while DpR and eETS were less correlated with OS (r2= 0.228, 0.082). PFS and eETS were thus chosen as variables for the prediction formula of prognosis. However, the present formula did not show an apparent increased R2 value compared with the formula consisted of PFS alone (adjusted R2= 0.442 vs 0.425), indicating that the present formula could not provide more accurate prediction. In the stratified subgroups according to treatment regimen and KRAS status, the formula did not show remarkable change in R2 value. Conclusions: The present formulae including DpR and eETS does not have superior predicting potential to PFS alone for prognosis of the whole mCRC patients.

Background: Progression free survival (PFS) has been recognized as a surrogate outcome in the therapy for metastatic or recurrent colorectal cancer (mCRC). As molecular target therapies have become to be widely used, new surrogate outcome such as early tumor shrinkage (ETS) and deepness of response (DpR) are proposed. However, their validity has not been fully proven. We have tried to develop a new prognosis predictive model consisting of the three factors, DpR, ETS and PFS, in the first-line chemotherapy of mCRC. Method: ETS was defined as the estimated relative change in the sum of longest diameters of target lesions at week 8 compared to baseline. DpR was defined as the relative change in the sum of longest diameters of target lesions at the nadir compared to baseline. We retrospectively evaluated mCRC patients who started any chemotherapy from January 1, 2005 to December 31, 2010. PFS, ETS, DpR in the first-line chemotherapy and OS were examined following the previous reports. Result: 47 patients were enrolled. 30 patients were KRAS wild type, 15 were KRAS mutant and 2 were unknown. In 39 patients excluding survival cases, chemotherapy regimen were oxaliplatin-based plus BV; 21, irinotecan-based plus BV; 6, oxaliplatin-based; 9, irinotecan-based; 3. Anti-EGFR therapies were not performed in the first-line chemotherapy. Median of DpR, PFS and OS were 34.3 %, 257 days, 587 days respectively. PFS showed a correlation with OS, while DpR and ETS were not correlated with OS. DpR and ETS were highly correlated to each other. Compared with prognosis predictive models consisted of PFS alone, the new model consisted of the three factors did not show increased R-squared value suggesting that the new model could not provide more accurate prediction. Conclusion: The present prognosis predictive model including DpR and ETS may not be adapted for the whole mCRC patients. Specific patient population may possibly be suitable for prognosis prediction by this model.

Background: Anti-EGFR antibody is approved for the treatment of patients with KRAS wild-type metastatic colorectal cancer. However, there are a few studies show the efficacy and safety of anti-EGFR antibody rechallenge after disease progression following anti-EGFR antibody based chemotherapy. Patients and methods: We assessed the efficacy and safety of anti-EGFR antibody rechallenge prospectively in patients with metastatic colorectal cancer refractory to anti-EGFR antibody and chemotherapy including oxaliplatin (L-OHP), irinotecan (CPT-11) and FU plus or minus bevacizumab between May 2010 and January 2013. Result: Thirteen patients were enrolled. Nine patients were male and 4 patients were female. The median age of patients was 60 years old, ECOG performance status 0/1; 3/10. The median number of previous chemotherapies was 3 (2-5). All patients received prior anti-EGFR antibody therapy, cetuximab (Cmab) + CPT-11; 10 (PR 4), Cmab/Panitumumab (Pmab) + FOLFOX;2 (PR 2) and Pmab monotherapy; 1 (SD), PFS was 168 days. Anti-EGFR antibody rechallenge therapy were Cmab/Pmab + capecitabine/S-1 (7), Pmab + FOLFOX (3), Cmab + CPT-11 (2), Pmab monotherapy (1). No CR/PR was obtained, 7 patients had stable disease and 6 patients had progressive disease. Four patients had a minor response. Median overall survival was 228 days and median progression-free survival was 102 days. Adverse events over grade 3 were platelet count decreased (1), paronychia (1), peripheral sensory neuropathy (1), and ileus (1). Conclusion: The efficacy of anti-EGFR antibody rechallenge is limited in chemorefractory patients with metastatic colorectal cancer.

TPS3654 Background: Pmab and Cmab are known to be effective in KRAS WT mCRC. Recent study showed that Pmab and Cmab monotherapy were comparable in patients with KRAS WT mCRC previously treated with...

e15170 Background: In Japan, the elderly population is increasing, and steadily increase the number of deaths in the elderly gastric cancer patients. However, the standard treatment of elderly gastric cancer has not been established, either treatment of S-1 or SP is carried out in the clinical practice, while SP is considered as standard therapy in the young people. Now, we investigated the impact of S-1 and SP on survival time in clinical practice. Methods: Between 2003 and 2012, advanced gastric cancer patients over 70 years of age received S-1 or SP as first line therapy were retrospectively reviewed to investigate clinical outcomes. Patient characteristics analyzed included age, gender, performance status (PS), tumor histology, renal function and metastatic site. In addition, we have analyzed prognostic factors in multivariate analysis. Results: Among 93 patients (pts), 67 pts (72%) received S-1 and 26 pts (28%) received SP. Patient characteristics between the two groups showed no significant differences in gender, histology, metastatic site, or creatinine clearance level, but did show an imbalance in PS (tended with better at SP group) and age (tended with younger at SP group), significantly. Even though the background factors were favorable results in SP group, there were no significant differences in median progression-free survival (median 139 vs. 102 days; p = 0.96) and overall survival (median 330 vs. 263 days; p = 0.55) between S-1 and SP group, respectively. Grade 3-4 neutropenia (10 vs. 27%, p < 0.05) , fatigue (3 vs. 15%, p < 0.05) and Grade 1-2 creatinine increased (9 vs. 31%, p < 0.01) were more frequent in the SP group than in the S-1 group, respectively. According to the multivariate analysis, exposure to CDDP was not independently associated with a better prognosis. Conclusions: Despite the obvious limitations of this analysis, there does not appear to be a benefit for the addition of CDDP in the elderly gastric cancer patients due to the increase of toxicity. A randomized controlled trial in this age group is warranted. We will also report the results of clinically meaningful prognostic factors associated with the primary treatment at annual meeting.

Background Approval of trastuzumab (Her) following ToGA trial was a milestone of chemotherapy for advanced/recurrent gastric cancer. In this presentation, we report the practice, in Kyushu Cancer Center, of HER2 screening, safety and efficacy of Her-combined chemotherapy, and discuss on the problems of clinical practice. Methods We examined HER2-immunohistochemistry (IHC) on 90 cases of advanced/recurrent gastric cancer which were under chemotherapy on March 2011 or initiated chemotherapy until January 2012 at Kyushu Cancer Center. HER2 fluorescent in situ hibridization (FISH) was tested when IHC result was 2+. Her-combined chemotherapy was planned to HER2-high cases (IHC 3+ or IHC2+ and FISH positive). Results IHC results of 90 cases were 3 + : 12, 2 + : 6, 1 + : 11 and 0: 61 cases, respectively. Five positive FISH results were obtained out of six IHC 2+ cases. We experienced 17 HER2-high cases (18.9%). Her-combined chemotherapy was planned as first-line therapy (11 cases) or subsequent lines (3 cases), gaining 6 PR. Only three cases were started initial therapy as Her-combined, and others were started with chemotherapy alone and added Her later. As adverse events, three infusion reactions and no cardiac toxicity was observed. Conclusions An equivalent HER2-high rate as previous reports was observed in our practice. Many cases did not allow delay in initiation of chemotherapy during HER2 testing, and chemotherapy was often started without HER2 results. Further practical experiences and new evidences were needed in the point of chemotherapy initiation. Her-combined chemotherapy was safely carried out, and its efficacy must be confirmed by further accumulation of trials and practical experiences.

3742 Background: A previous phase I trial in patients (pts) with metastatic colorectal cancer (CRC) demonstrated that weekly CPT-11 and bolus 5FU/l-LV administered for 3 weeks every 28 days (modifi...