D.B. Shin

615ORANDOMIZED PHASE II STUDY OF CAPECITABINE AND CISPLATIN WITH OR WITHOUT SORAFENIB IN PATIENTS WITH METASTATIC GASTRIC CANCER: STARGATE STUDY

ABSTRACT Aim: Capecitabine and cisplatin (XP) combination chemotherapy is one of the standard 1st line regimens for the treatment of metastatic gastric cancer (MGC). Sorafenib is a multi-kinase inhibitor with activity against angiogenesis and RAF-MEK-ERK pathway. In this study, we aimed to evaluate the efficacy of sorafenib (S) in combination with XP as the 1st line chemotherapy in MGC. Methods: This study was a randomized (1:1), open-label, phase II study. The patients (pts) with metastatic gastric or gastroesophageal junction adenocarcinoma with measurable lesion(s) were eligible. The primary endpoint was progression-free survival (PFS). XP + S consisted of capecitaine 800 mg/m2 po bid on days 1-14, cisplatin 60 mg/m2 iv on day 1, and sorafenib 400 mg po bid on days 1-21, every 3 weeks. XP consisted of capecitabine 1000 mg/m2 on days 1-14, and cisplatin 80 mg/m2 iv on day 1, every 3 weeks. XP was continued up to 8 cycles until disease progression or intolerance. Pts in XP arm were allowed to cross over to sorafenib alone when their diseases progressed. Results: Between Jan 2011 and Feb 2013, a total of 195 pts were randomized from 12 sites in Korea, China and Taiwan. Median age was 56 years. All pts had ECOG performance status 0-1. 19% of pts had prior gastrectomy. Overall response rate was 54% in XP + S arm, and 52% in XP arm (p = 0.826). With a median follow-up of 12.6 months (range, 0.1-29.2), median PFS assessed by independent review was 5.6 months in XP + S arm, and 5.3 months in XP arm (HR 0.92, 95% CI 0.67-1.27, p = 0.609). OS was not different between the two arms (median 11.7 vs. 10.8 months; HR 0.93, 95% CI 0.65-1.31, p = 0.661). Frequencies of grade 3/4 toxicities were similar between XP + S and XP arms, except neutropenia (21% vs 37%), febrile neutropenia (2% vs 6%), and palmar-plantar erythrodysesthesia syndrome (7% vs 1%). In 51 pts who crossed over to sorafenib alone in XP arm, there was no objective response and the median PFS was 1.3 months (95% CI, 1.2-1.7). Conclusions: The addition of sorafenib to XP chemotherapy was safe but not more effective than XP chemotherapy alone for the 1st line treatment of MGC. Biomarker analyses are now ongoing to identify potential patients who can get benefit with XP + S. Disclosure: Y. Kang: Honorarium, consultant for Bayer, Roche Research grant from Bayer, Roche. All other authors have declared no conflicts of interest.

Epirubicin (E), cisplatin (C) and capecitabine (X) in first-line chemotherapy for patients with advanced gastric cancer

4074 Background: ECF has been regarded as a highly active regimen for the advanced gastric cancer. Capecitabine (X) is an oral fluoropyrimidine carbamate and may be less toxic and more active than infusional 5-FU. We evaluated the antitumor activity and toxicity of ECX combination for untreated patients (pts) with advanced gastric cancer. METHODS Eligibility included (a) histologically proven gastric adenocarcinoma, (b) locally unresectable, metastatic or relapsed disease after resection, (c) measurable disease, (d) no previous chemotherapy or radiation therapy, (e) PS ECOG 0-2, (f) aged 18 years or older, and (g) no contraindication to chemotherapy. Pts received E (50 mg/m2 IV on D1), C (60 mg/m2 IV on D1) and X (2,000 mg/m2/day PO on D1-14) every 3 weeks. RESULTS Between May 2001 and January 2003, 54 pts were enrolled in this study; median age was 56 years (range, 32 to 73) with 41 male and 13 female pts; 32 metastatic diseases, 20 relapsed diseases after surgery and 2 locally advanced diseases. A total of 250 cycles were administered with a median of 4 cycles per patient (range, 1-12). Fifty-three pts were assessable for toxicity and 50 for responses. The most common grade 3/4 hematological adverse event was neutropenia in 76 cycles (31%). Grade 3/4 leukopenia and febrile neutropenia occurred in 27 cycles (11%) and 11 cycles (4.8%), respectively. Non-hematological toxicity was generally mild and reversible. Grade 3/4 nausea, vomiting and stomatitis occurred in 8%, 9%, and 8% of the patients, respectively. Hand-foot skin reaction developed in 51% of patients, but grade 3 occurred only in 4%. One patient died of neutropenic sepsis. The overall best response rate by intent-to-treat analysis was 59% (95%CI, 46-72%) including 52% of PR and 7% of CR. Median follow-up was 16 months (range 8 to 28 months). Median response duration and time to progression was 5.8 months (95%CI, 4.7-6.9) and 6 months (95% CI, 3.8-8.2), respectively. Median survival for all patients was 9.6 months (95% CI, 8.7-10.5). CONCLUSIONS ECX combination regimen showed high anti-tumor activity with a tolerable toxicity as a front line chemotherapy for pts with advanced gastric cancer. No significant financial relationships to disclose.

Interim analysis from a prospective randomized trial of taxanes plus 5-FU in advanced gastric cancer

4193 Background: Paclitaxel and docetaxel has been shown to be effective in some patients with advanced gastric cancer. We used a randomized phase II design to prospectively compare the toxicity and efficacy of taxanes (paclitaxel or docetaxel) plus 5-FU. METHODS Based on results from our previous phase I study, patients with metastatic or recurrent gastric cancer were randomly assigned to one of two treatments. A 2-stage study design was utilized. In the first stage, 25 patients were randomized to receive paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 in combination with infusional 5-FU 500 mg/m2/day for 5 days. Treatment was repeated every 3 weeks. In the presence of one or more responses observed in each groups, additional 19x2 patients should be enrolled and treated, so that the probability of response rate is 10% or higher. RESULTS Of Among 11 patients assessable for response in the paclitaxel group, 2 (18%) patients responded. With docetaxel, 4 (33%) of 12 assessable patients responded. The median time to treatment failure was 3.5 (paclitaxel) and 4.4 months (docetaxel). In 97 treatment cycles delivered (median: 3 in paclitaxel group, 5 in docetaxel group), dose reduction was required in 31 (32%) cycles and median relative dose intensities for paclitaxel, docetaxel and 5-FU were 89%, 88% and 72%, respectively. One patient in each groups died of toxicity during treatment and there were 30 episodes (31%) of grade 3/4 toxicity primarily stomatitis, asthenia, and neutropenia. CONCLUSIONS The combination with docetaxel and 5-FU suggests a trend towards better tolerability and efficacy. The reasons for the poor results in this patient population are unclear, given the relatively good performance status of the patients studied. Alterations in dosing schedule may be needed to enhance activity with tolerable side effects. No significant financial relationships to disclose.

A phase II open-label randomized multicenter trial of TSU-68 in combination with S-1 and oxaliplatin versus S-1 in combination with oxaliplatin in patients with metastatic colorectal cancer.

492 Background: Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths worldwide. Oxaliplatin-based treatment (FOLFOX, CapeOX) combined with bevacizumab is one of the standard chemotherapies for metastatic CRC. However, several clinical studies performed using S-1 plus oxaliplatin (SOX) indicate that SOX is a treatment option for metastatic CRC. TSU-68 (orantinib) is an oral compound that inhibits vascular endothelial growth factor receptor and platelet-derived growth factor receptor and has promising efficacy and high safety. The recommended phase II dose of TSU-68 plus SOX has been determined in a phase I study. This trial aimed to evaluate the efficacy of TSU-68 in combination with SOX. Methods: We performed an open-label multicenter randomized phase II trial in Korea. Treatment-naive metastatic CRC patients with a performance status 0 or 1 were randomized in a ratio of 1:1 to receive either TSU-68 plus SOX (group A) or SOX (group B). The primary endpoint was progression-free surv...

Assessing Concordance With Watson for Oncology, a Cognitive Computing Decision Support System for Colon Cancer Treatment in Korea

PURPOSE IBM Watson for Oncology (WFO) is a clinical decision-support computing system that provides oncologists with evidence-based treatment recommendations for a variety of cancer diagnoses. The evidence-based supported treatment recommendations are presented in three categories: Recommended, representing the Memorial Sloan Kettering Cancer Center (MSKCC) preferred approach; For Consideration, evidence-based alternative treatments; and Not Recommended, alternative therapies that may be unacceptable. We examined the absolute concordance of treatment options with that of the recommendations of a multidisciplinary team of oncologists from Gachon University, Gil Medical Centre, Incheon, South Korea. METHODS We enrolled 656 patients with stage II, III, and IV colon cancer between 2009 and 2016. Cases were processed using WFO and, using retrospective clinical data, outputs were compared with the actual treatment the patient received. Absolute concordance was defined as an alignment of recommendation in the Recommended MSKCC preferred-approach category. Treatment recommendations that were represented in the For Consideration category were not the focus of this study. RESULTS The absolute concordance between the WFO-derived MSKCC preferred approach and Gil Medical Centre treatment recommendations was 48.9%. The percentage of cases found to be acceptable was 65.8% (432 of 656) and the stage-specific concordance rate was 32.5% for patients with stage II disease who had risk factors and 58.8% for patients with stage III disease. Patients 70 years of age and older had a concordance rate of only 20.2%, whereas younger patients had a concordance rate of 63.8% ( P = .0001). CONCLUSION The main reasons attributed to the low concordance rate were age, reimbursement plan, omitting chemotherapy after liver resection, and not recommending biologic agents (ie, cetuximab and bevacizumab).

Metastasectomy for recurrent or metastatic biliary tract cancers: A single center experience

PURPOSE To assess efficacy or long-term result of metastasectomy for recurrent or metastatic biliary tract carcinoma (BTC), we conducted a retrospective review of the outcomes of metastasectomy for recurrent or metastatic BTCs, comprising intrahepatic cholangiocellular carcinoma (IHCCC), proximal and distal common bile duct cancer (pCBDC and dCBDC), gallbladder cancer (GBC), and ampulla of Vater cancer (AoVC). PATIENTS AND METHODS The clinicopathological features and outcomes of BTC patients who underwent surgical resection for the primary and metastatic disease at the Gachon University Gil Medical Centre from 2003 to 2013 were reviewed retrospectively. RESULTS We found 19 eligible patients. Primary sites were GBC (seven patients, 37%), IHCCC (five patients, 26%), dCBDC (three patients, 16%), pCBDC (two patients, 11%), and AoVC (two patients, 11%). Eight patients (42%) had synchronous metastasis whereas 11 (58%) had metachronous metastasis. The most common metastatic site was liver (nine patients, 47%), lymph node (nine patients, 47%), and peritoneum (three patients, 16%). Nine patients (47%) achieved R0 resection, whereas four (21%) and six (32%) patients had R1 and R2 resection, respectively. With a median follow-up period of 26.7 months, the estimated median overall survival (OS) was 18.2 months (95% confidence interval, 13.6-22.9 months). Lower Eastern Cooperative Oncology Group performance status (P = 0.023), metachronous metastasis (P = 0.04), absence of lymph node metastasis (P = 0.009), lower numbers of metastatic organs (P < 0.001), normal postoperative CA19-9 level (P = 0.034), and time from diagnosis to metastasectomy more than 1 year (P = 0.019) were identified as prognostic factors for a longer OS after metastasectomy. CONCLUSIONS For recurrent or metastatic BTCs, metastasectomy can be a viable option for selected patients.

AOSOP5 A PHASE 2 TRIAL OF SALVAGE TREATMENT WITH GEMCITABINE AND S-1 COMBINATION IN HEAVILY PRETREATED PATIENTS WITH METASTATIC COLORECTAL CANCER

2 ) was given on days 1 and 8, every 21 days, until disease progression and for a maximum of nine cycles. The primary endpoint was objective response rate (ORR). Results. The median number of cycles was 5 (range 1−9), ORR was 16.7% (95% confidence interval (CI) 4.5-28.9), and disease control rate was 61.1% (95% CI 45.2-77.0) with six partial responses and 16 stable disease. Median duration of disease control was 5.8 months (95% CI 4.1−7.5). Median progression-free survival was 3.7 months (95% CI 2.2−5.2) and median overall survival was 10.0 months (95% CI 7.4-12.7). Grade 3−4 toxicities were rare (neutropenia 12%, anaemia 11%, leucopenia 6%, thrombocytopenia 3%, and diarrhoea 3%). Discussion. Combination chemotherapy with gemcitabine and S-1 was convenient, well tolerated, and efficacious for heavily pretreated patients with mCRC. This regimen warrants further evaluation in patients with good performance status but no further treatment options.

6583 POSTER Phase I Dose-finding Study of Epirubicin, Oxaliplatin and S-1 (EOS) in Patients With Previously Untreated Advanced Gastric Cancer (AGC)

(13p/4p: 5Fu/xeloda w or w/o platinum compounds). From these, 43p were evaluable for response, 33p had SD and 10p had PD. PFS for 2 line CT was 6mo (95%CI 4.1−7.9). PFS for FU based regimen 2 line was 3.2mo (95%CI 0.2−6.9) and for Gem based regimen 2 line: 6.1 mo (95%CI 3.1−9) p = 0.09. OS, for all 96pts was 9.9mo (95%CI 8.8−11) and for 46p with 2 line CT was 13.6mo (95%CI 11.2−16) with better OS for pts with FU based 1 line and Gem in 2 line: 19mo (95%CI 8.9−2) vs 13.2mo (95%CI 12–14.4) p < 0.001 (s). Conclusions: Our results indicate that the FU based CT in 1 line and Gem in 2 line gave a better survival than the opposite, therefore this nonrandomized trial showed that this regimens’ order could be relevant and necessitates a phase III trial randomized to check the impact of CT lines sequence in advanced BTC.