Search

541 Background: Relapse after highly invasive surgery for biliary tract cancers (BTCs), especially in the early postoperative period, causes medical, psychological, social, and economic disadvantages to the patients. However, approximately 30% of patients with curatively resected BTCs experience relapse within the first 12 months. JCOG1202 (UMIN000011688) is a randomized phase III trial conducted in patients with resected BTCs showing the benefit of adjuvant S-1 for overall survival. This study aimed to investigate the risk factors for early relapse of resected BTCs in the JCOG1202 cohort. Methods: Of the 440 patients enrolled in the JCOG1202, 217 patients who received surgery alone (arm A) and 207 patients who received adjuvant S-1 (arm B) were eligible and included in this analysis. Early relapse was defined as relapse or death within 12 months after enrollment. Predictive factors for early relapse were assessed using logistic regression analyses. Results: Postoperative early relapse was observed in 59 (27.2%) and 38 (18.4%) of patients in arm A and arm B, respectively. In multivariable logistic regression analysis for the 424 eligible patients, postoperative CA19-9 levels >37 u/ml (odds ratio (OR): 2.790, 95% confidence interval (CI): 1.262-6.170), poorly differentiation (vs. well-differentiated/papillary) (OR: 4.746, 95% CI:1.927-11.688), moderate differentiation (vs. well-differentiated/papillary) (OR: 1.955, 95% CI:1.071-3.567), lymph node metastases > 4 (vs. 0) (OR: 3.991, 95% CI: 1.674-9.514), lymph node metastases 1-3 (vs. 0) (OR: 2.661, 95% CI: 1.471-4.814), and presence of residual tumor (OR: 2.171, 95% CI: 1.070-4.408) were independent risk factors for early relapse. Importantly, adjuvant S-1 chemotherapy significantly reduced early relapse (OR: 0.491, 95% CI: 0.290-0.833). Similar results were observed in arm B. Conclusions: Postoperative CA19-9 level, tumor differentiation, lymph node metastases, and the residual tumor significantly impact early relapse in patients with curatively resected BTCs. Although adjuvant S-1 chemotherapy was effective in reducing early relapse, similar factors tended to be the risk factors in patients receiving adjuvant S-1 chemotherapy. Patients at high risk of early relapse may need more intensive perioperative therapy. Clinical trial information: UMIN000011688 .

382 Background: Capecitabine is usually used for patients with curatively resected biliary tract cancer (BTC) in EU and US, but no clear survival benefit has been shown in phase III trials. S-1, an oral fluoropyrimidine derivative, has shown promising efficacy, with a mild toxicity profile, in patients with advanced BTC. The aim of this trial was to confirm whether adjuvant S-1 therapy might improve the overall survival (OS) in patients with curatively resected BTC. Methods: This open-label, multicenter, randomized phase III trial was conducted in 38 Japanese hospitals. Eligible patients were aged 20 to 80 years old, had undergone R0/R1 resection for histologically confirmed adeno(squamous) carcinoma of the extrahepatic bile duct, gallbladder or ampulla of Vater (T2-4, N0, M0 or T1-4, N1, M0) or the intrahepatic bile duct (T1-4, N0-1, M0) (7th UICC classification), and had an ECOG performance status (PS) of 0 or 1.The calculated sample size was 440 to detect hazard ratio for OS of 0.74 with one-sided alpha of 5% and a power of 80%. Patients in surgery-alone arm received no further anti-cancer treatment, while those in adjuvant S-1 arm received 4 cycles of oral S-1 chemotherapy at the dose of 40 mg/m2 twice daily for 4 weeks, followed by 2 weeks of rest. Primary endpoint was OS, and secondary endpoints were relapse-free survival (RFS), incidence of adverse events, and proportion of treatment completion. Results: A total of 440 patients (surgery-alone, n = 222; adjuvant S-1, n = 218) were enrolled from September 2013 to June 2018. The data cutoff date was June 23, 2021, and the median follow-up duration was 45.4 months. Of all randomized patients, OS was significantly longer with adjuvant S-1 than surgery-alone (hazard ratio [HR] 0.694, 95%CI, 0.514-0.935; one-sided p = 0.008; the 3-year OS, 67.6% [surgery-alone; 95%CI, 61.0-73.3%] and 77.1% [adjuvant S-1; 95%CI, 70.9-82.1%]). Adjuvant S-1 was also better for RFS (HR 0.797 [95%CI, 0.613-1.035], 3-year RFS, 50.9% [surgery-alone; 95%CI, 44.1-57.2%] and 62.4% [adjuvant S-1; 95%CI, 55.6-68.4%]). All preplanned subgroup analyses (PS, age, cancer type, cancer stage, R factor, and serum CA19-9) revealed favorable OS and RFS for adjuvant S-1 arm. The main grade 3-4 adverse events in adjuvant S-1 arm were biliary tract infection (7.2%), diarrhea (2.9%), appetite loss (2.9%), fatigue (2.9%), and the treatment was well-tolerated. Conclusions: Adjuvant S-1 therapy led to significantly longer survival than surgery alone and becomes the standard of care for resected BTC. Clinical trial information: UMIN000011688.

366 Background: Recent improvements in chemotherapy for initially unresectable pancreatic ductal adenocarcinoma (UPDAC) occasionally show remarkable antitumor effect and lead to conversion surgery (CS). However, the optimal indication and clinical impact of CS remains unknown. We have recently developed a new regimen consisted of biweekly S-1, oxaliplatin, and irinotecan (SOXIRI). In this regimen, we used S-1 in alternate-day administration instead of 5-FU, that can be more feasible than FOLFIRINOX. The aim of this study was to evaluate the clinical impact of CS after SOXILI treatment for initially UPDAC. Methods: We conducted an open-label, single-arm, phase II study that was carried out at Nara Medical University and Kansai Medical University in Japan. Patients with untreated metastatic and locally advanced PDAC were enrolled. They received 80 mg/m2 twice a day of S-1 for 2 weeks in alternate-day administration, 150 mg/m2 of irinotecan on day 1, and 85 mg/m2 of oxaliplatin on day 1 of a 2-week cycle. Results: The 35 enrolled patients received a median of six (range: 2-15) treatment cycles. The RR was 22.8%; median OS, 17.7 months; and median PFS, 7.4 months. Major grade 3 or 4 toxicity included neutropenia (54%), anemia (17%), febrile neutropenia (11%), anorexia (9%), diarrhea (9%), and nausea (9%). Twenty-three out of 35 patients of UR-PDAC were unresectable locally advanced pancreatic cancer (UR-LAPA). Seven out of 23 patients with UR-LAPA underwent CS. Distal pancreatectomy with celiac axis resection was performed in three patients, central pancreatectomy was performed in one patient. Pancreatoduodenectomy (PD) was performed in two patients, and PD with portal vein resection in one patient. Two out of seven patients had postoperative complications. One case had grade B pancreatic fistula, and the other case underwent cholecystectomy due to acute cholecystitis. The median OS in patients who received CS was 31.4 months. Conclusions: SOXIRI regimen has shown promising clinical efficacy with acceptable tolerability in patients with unresectable pancreatic cancer. Furthermore, it may be a potent first-line treatment when considering conversion surgery. Clinical trial information: UMIN000014339.

349 Background: JCOG1113 is a randomized phase III trial to confirm the non-inferiority of gemcitabine plus S-1 (GS) to gemcitabine plus cisplatin (GC) for advanced biliary tract cancer (BTC) in overall survival (OS). In the final analysis, GS demonstrated non-inferiority to GC in OS and was considered as a new option of standard of care for advanced BTC. However, there are few reports on the efficacy and safety of combination chemotherapy in elderly patients with advanced BTC. Therefore, this study aimed to explore the clinical outcomes of combination chemotherapy in elderly patients with advanced BTC. Methods: Among all enrolled patients in JCOG1113, ≥ 75 years old patients were included in this exploratory subgroup analysis. Cox regression analysis was performed to investigate the influence of age at baseline on OS and PFS. Clinically relevant adverse events (AEs) were defined as any of grade 2 or more fatigue, appetite loss, nausea, vomiting, oral mucositis, and diarrhea, and were compared using Fisher’s exact test. Results: Among all enrolled patients, 155 patients in GC and 139 patients in GS were included in < 75 years old cohort and 20 patients in GC and 40 patients in GS were included in ≥ 75 years old cohort.The HR of ≥ 75 years old cohort to < 75 years old cohort for OS was 0.96 (95% CI 0.71–1.30) in all enrolled patients. The HR of ≥ 75 years old cohort to < 75 years old cohort for OS was 1.26 (95% CI 0.77–2.04) in GC, and 0.84 (95% CI 0.56–1.24) in GS. The HR of ≥ 75 years old cohort to < 75 years old cohort for PFS was 1.01 (95% CI 0.63–1.61) in GC, and 0.78 (95% CI 0.54–1.12) in GS. Clinically relevant AEs were 36.1% in < 75 years old cohort and 25.0% in ≥ 75 years old cohort in GC, and 29.5% in < 75 years old cohort and 32.5% in ≥ 75 years old cohort in GS. Conclusions: The clinical outcomes of combination chemotherapy in elderly patients were comparable to non-elderly patients. Clinical trial information: 000010667.

368 Background: JCOG1113 is a randomized phase III trial to evaluate gemcitabine (GEM) plus S-1 (GS) versus GEM plus cisplatin (GC) regarding overall survival (OS) for advanced biliary tract cancer (BTC) (UMIN000001685) and the non-inferiority of GS was demonstrated. It is necessary to consider renal function using cisplatin or S-1 because cisplatin has renal toxicity, and the toxicity of S-1 is affected by renal function. Therefore, we evaluated the influence of renal function on the efficacy and safety of GC and GS in JCOG1113. Methods: All enrolled patients (pts) in JCOG1113 (n = 354) were analyzed. Eligibility criteria included chemotherapy-naïve pts with recurrent or unresectable biliary tract adenocarcinoma, ECOG-PS of 0–1, CCr > 50 ml/min, and adequate organ function. Renal function was classified into two groups by creatinine clearance (CCr) as calculated by the Cockcroft-Gault formula; high CCr (CCr ≥ 80 ml/min) or low CCr (80 > CCr ≥ 50 ml/min). The impact of renal function on OS and progression-free survival (PFS) were compared using the Cox regression model. The adverse events (AEs) were compared using Fisher’s exact test. Results: Eighty-eight pts on GC and 88 pts on GS were included in the high CCr group, and 87 pts on GC and 91 pts on GS were included in the low CCr group. There were no differences between the groups regarding, sex, PS, primary site, biliary drainage, operation, or recurrence, except for age. The hazard ratio (HR) of GS to GC for OS was 1.12 (95% CI 0.81–1.56) in the high CCr group and 0.80 (95% CI 0.58–1.11) in the low CCr group. The HR of GS to GC for PFS was 1.06 (95% CI 0.78–1.44) in the high CCr group and 0.69 (95% CI 0.50–0.94) in the low CCr group. Grade 3-4 AEs of white blood cell count decreased (35.3%/23.6%), anemia (29.4%/7.9%) and platelet count decreased (18.8%/10.1%) were more common in GC than GS in the low CCr group. In contrast, the incidence of all grade 3-4 non-hematological AEs was higher (36.0%/11.8%) in GS than GC in the low CCr group ( p = 0.0002). Conclusions: GS was better in terms of OS, PFS, and hematological toxicities than GC in the low CCr group. GS might be recommended for the population with lower renal function in the treatment for advanced BTC.

205 Background: Gemcitabine (GEM) plus cisplatin (GC) is the standard of care for advanced biliary tract cancer (BTC). However, GC is considered to be toxic because of nausea, vomiting, and appetite loss, and inconvenient due to requiring hydration before and after administration. GEM plus S-1 (GS) was reported to be promising with preferable efficacy and acceptable toxicity profile (UMIN000001685). This phase III study aimed to confirm the non-inferiority of GS to GC in terms of overall survival (OS). Methods: Eligibility criteria included chemotherapy-naïve patients with recurrent or unresectable biliary tract adenocarcinoma (gallbladder, intrahepatic biliary tract, extrahepatic biliary tract, or ampulla of Vater), an ECOG-PS of 0–1, and adequate organ function. In the GC arm, 1 g/m2 of GEM and 25 mg/m2 of cisplatin was infused on days 1 and 8 of a 21-day cycle. In the GS arm, 1 g/m2 of GEM was infused on days 1 and 8, and S-1 60, 80, or 100 mg/day according to body-surface area was administered from days 1 to 14 of a 21-day cycle. The primary endpoint was OS and the secondary endpoints included progression-free survival (PFS), response rate (RR), adverse events (AEs), clinically relevant AEs defined as any of grade 2 or more fatigue, appetite loss, nausea, vomiting, oral mucositis, and diarrhea. The sample size was calculated to be 350 with a one-sided alpha of 5%, a power of 80%, non-inferiority margin of 1.155 in terms of hazard ratio (HR). Results: From May 2013 to March 2016, 354 patients were enrolled. The non-inferiority of GS to GC was demonstrated (median OS: 13.4 months (m) in GC and 15.1 m in GS, HR 0.95; 90% confidence interval (CI), 0.78 to 1.15; P = 0.046 for non-inferiority). Median PFS was 5.8 m in GC and 6.8 m in GS (HR 0.86, 95% CI, 0.70-1.07). RR was 32.4% in GC and 29.8% in GS. Preliminary AEs data demonstrated that both treatments were generally well tolerated, although clinically relevant AEs were observed 34.7% in GC and 31.2 % in GS. Conclusions: GS demonstrated non-inferiority to GC in OS with good tolerability and was considered as new convenient option of standard of care without hydration for advanced BTC. Clinical trial information: UMIN000010667.

TPS4144 Background: No standard adjuvant treatment has been established for patients with curatively resected biliary tract cancer (BTC). S-1, which is one of the oral fluoropyrimidine derivatives, showed promising efficacy with a mild toxicity profiles in patients with advanced BTC, and the survival benefit of adjuvant S-1 therapy has been demonstrated in patients with resected gastric cancer and pancreatic cancer. The aim of this open-label, multicenter, randomized phase III trial is to assess whether adjuvant S-1 would prolong the overall survival in patients with resected BTC. Methods: The main eligibility criteria are as follows: 1) curatively resected carcinoma of the extrahepatic bile duct, gallbladder or ampulla of Vater (T2-4, N0, M0 or T1-4, N1, M0), or carcinoma of the intrahepatic bile duct (T1-4, N0-1, M0) (7th UICC classification), 2) histologically confirmed adeno (squamous) carcinoma, 3) R0 or R1 residual disease, 4) age 20 to 80 years, 5) ECOG performance status 0 or 1, 6) no prior chemotherapy or radiotherapy, 7) adequate organ functions, 8) written informed consent. Patients are randomly assigned to the surgery alone arm (arm A) or the adjuvant S-1 arm (arm B) by the minimization method for balancing institution, primary site of cancer and lymph node metastasis between the arms. Patients in arm A do not receive any anti-cancer treatment, while patients in arm B receive 4 cycles of oral S-1 chemotherapy at the dose of 40 mg/m2 twice daily for 4 weeks followed by 2 weeks of rest. The primary endpoint is overall survival, while the secondary endpoints are relapse-free survival, incidence of (serious) adverse events, and proportion of treatment completion. We assumed a 3-year survival in arm A of 47% and a 10% increase in the 3-year survival in arm B. The sample size was calculated as a total of 350, with a one-side alpha of 5% and power of 70%; planned accrual period is 4 years, and follow-up period, 3 years. Primary analysis will be conducted at 3 years and updated analysis will be conducted at 5 years after closing of accrual. As of Jan 31, 2016, a total of 285 patients have already been enrolled in this trial from Sep 2013. Clinical trial information: UMIN000011688.

4123 Background: JCOG1106 is a randomized selection phase 2 trial to evaluate the efficacy and safety of CRT (S-1 concurrent RT) with (Arm B) or without (Arm A) induction CT of gemcitabine (GEM) for LAPC. In the final analysis, we selected Arm A as a promising regimen due to a poorer 2-year overall survival (OS) of Arm B, in spite of a favorable 1-year OS with crossing of the survival curves around 1-year (Ioka, ESMO2016). Therefore, this study aimed to explore subgroups benefit more from either treatment. IN statuses defined by such as serum C-reactive protein (CRP) and serum albumin (Alb) are recognized as prognostic and predictive factors in patients (pts) with various cancers receiving CT or CRT. We hypothesized that IN status may modify the effect of induction CT. Methods: Subjects were all eligible pts who were enrolled in JCOG1106 (n = 51/49 in Arm A/B). Glasgow Prognostic Score (GPS) was classified by baseline CRP and Alb. Pts with a CRP ≤ 10 mg/L and Alb ≥ 35 g/L were allocated to GPS 0, with a CRP > 10 mg/L or Alb < 35 g/L to GPS 1, and with a CRP > 10 mg/L and Alb < 35 g/L to GPS 2. This exploratory subgroup analysis was performed by Cox regression analysis to investigate the impact of IN status at baseline on OS. Less than 0.1 of P-value for interaction was regarded as significant. Results: GPS, CRP and Alb showed significant treatment interactions in terms of OS. HRs of Arm B to Arm A were 1.35 (0.82–2.23) and 0.59 (0.24–1.50) in the GPS 0 (n = 44/34 in Arm A/B) and GPS 1/2 group (n = 7/15) ( P-interaction = 0.06). HRs were 2.57 (1.36–4.86) and 0.70 (0.37–1.32) in the low CRP group (≤ 1.35 mg/L, n = 25/25) and high CRP ( > 1.35 mg/L, n = 26/24) ( P= 0.01). HRs were 1.62 (0.77–3.40), 2.70 (1.17–6.23) and 0.52 (0.24–1.13) in the 1st (≤ 0.7 mg/L, n = 16/16), 2nd ( > 0.7, ≤ 3.0 mg/L, n = 20/16), and 3rd tertiary CRP group ( > 3.0 mg/L, n = 15/17) ( P= 0.01). HRs were 2.29 (1.11–4.69) and 0.89 (0.51–1.54) in the high Alb group ( > 40 g/L, n = 23/17) and low Alb (≤ 40 g/L, n = 28/32) ( P= 0.04). Arm B showed better survival in subgroups of GPS 1/2, higher CRP or lower Alb compared to Arm A. Conclusions: Pts with poor IN status may have treatment benefit of induction CT followed by CRT for LAPC. Clinical trial information: UMIN000006811.

3085Background: Wilms’ tumor gene (WT1) is overexpressed in almost all malignancies including PDAC, and is supposed to be most promising tumor-associated antigen in cancer immunotherapies. To inves...

4107Background: S-1 is an active agent for the treatment of pancreatic cancer. GEST study has previously shown the noninferiority of S-1 to gemcitabine in advanced pancreatic cancer. However, the s...

298 Background: The WHO classified pancreatic neuroendocrine Neoplasms (pNEN) in 2010 as G1, G2, and neuroendocrine carcinoma (NEC). However, pNEC is suspected to include heterogeneous disease entities, but is still not fully studied. We aimed to clarify the clinicopathological and molecular characteristics of NECs. Methods: A total of 100 cases clinical data and pathological slides originally diagnosed as NEC by the WHO in 2010(WHO-NEC) were retrospectively collected from 31 institutes. Expert pathologists were reassessed all cases slide using the designed protocol and reclassified as well differentiated NET (NET-G3), small cell NEC(SCNEC), and large cell NEC(LCNEC) by morphological features. Results: Thirty cases were eliminated mostly because acinar cell carcinoma, NET-G2 and malignant tumor not otherwise specified. Remaining 70 cases were subclassified into 21(30%) NET-G3, 31 (44.3%) SCNEC, 18(25.7%) LCNEC. Comparisons of NET-G3 vs. SCNEC vs. LCNEC revealed the following traits: ENETS stageⅣ: 76%, 81% and 78%; median Ki67 LI: 28.5% (15-53), 85 % (50-100) and 70.0 %(22-90); abnormal Rb expression: 0 %, 59% and 47%; KRAS mutations: 0 %, 48% and 50%; response rates to platinum-based chemotherapy: 0%, 60% and 44.4% ;and median survival(days): 1255, 340 and 196, respectively. When KRAS divided wild (n = 20) and KRAS mutation group (n = 42), response rate to platinum-based chemotherapy was 77% vs 23%.In the same manner, when Rb immune stain divided negative (n = 24) and positive (N = 41), response rate to platinum-based chemotherapy was 80% vs 23.8%. Besides response rate to platinum-based chemotherapy of KRAS mutation(+) and Rb immunopositivity(-) group (n = 7) were 100%, on the other hand, KRAS mutation(-) and Rb immunopositivity(+) group (n = 7) were 18.7%. Conclusions: In this retrospective study, WHO-NEC include 30% NET-G3. NET-G3 are genetically different from SCNEC and LCNEC. As for chemotherapy,Mutated KRAS and/or Rb immunonegativity in tumors with pNEC is associated with response to platinum-based chemotherapy.

4116 Background: Most patients (pts) with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy (CT) alone in Japan. Chemoradiotherapy (CRT) is also a treatment option, but the ro...

e15267 Background: Based on the results of the GEST study, S-1 was confirmed to be non-inferior to gemcitabine. However, the recommended standard regimen frequently causes adverse events(AEs). On the other hand, a multi-center prospective phase II study showed that the alternate-day administration of S-1 reduced AEs and was tolerable for unresectable advanced pancreatic ductal adenocarcinoma (PDAC) patients. Accordingly, we conducted a multi-center randomized phase II study to investigate the non-inferiority of S-1 using alternate-day administration, compared with the standard regimen for unresectable PDAC. Herein, we report the interim safety analysis results of this study. Methods: Patients who met the study criteria (histologically-confirmed PDAC, age > 20, ECOG Performance Status of 0 or 1, no prior chemotherapy or radiotherapy, and adequate organ functions) were randomly assigned at a ratio of 1:2 to standard daily S-1 administration (Arm A: 4 weeks of administration followed by 2 weeks of rest) or a...

252 Background: Based on the results of GEST, S-1 was confirmed to be non-inferior to gemcitabine. However, the recommended regimen of 4 weeks of administration interrupted by 2 weeks of drug withdrawal frequently causes adverse effect. Grade3/4 toxicities (%) in S-1 were neutropenia 8.8, anorexia 11.4, diarrhea 5.5. On the other hand, we experienced in clinical practice that the alternate-day administration of S-1 reduced adverse effects and was tolerable for unresectable advanced pancreatic cancer patients unwilling to continue the standard daily administration. We therefore conducted a multi-center cooperative prospective study to compare daily with alternate-day administration of S-1 for unresectable advanced pancreatic cancer. Methods: Patients with unresectable advanced pancreatic cancer (PS, 0 to 1; age, 20 to 80 years; no other therapy) were eligible for enrollment in this trial. S-1 was administered a dose of 40 to 60 mg twice daily, assigned according to body-surface area, on Monday, Wednesday, Friday, and Sunday (specified days). Each treatment cycle will be 42 days (6 weeks). The primary endpoint was overall survival (OS). Secondary endpoints were safety, response rate (RR), progression free survival (PFS), time to treatment failure (TTF). Results: A total of 50 patients were enrolled from Sep 2009 to Feb 2011. 48 patients were evaluable for response. Male/Female was 21/27, PS: 0/1 was 40/8. With a median follow-up time of 28.2 months, OS as primary endpoint was 8.4 months (95% CI, 5.4-10.8) with the 1 year survival rate 29.2%. PFS was 5.5 months, and TTF was 3.9 months. RR was 10.4% (95% CI: 3.5-19.1), and Disease Control rate was 79.2%. Grade 3/4 hematological and non-hematological toxicities were minor. All of those adverse reactions were tolerable and reversible. Conclusions: We will report the data from the final analysis at this meeting. The current data show mitigation of adverse effects with alternate-day administration of S-1, and it appears to be a more sustainable option for unresectable advanced pancreatic cancer. A randomized phase II trial comparing this regimen of S-1 with standard regimen of S-1 is ongoing. Clinical trial information: 000003453.

4007 Background: S-1, an oral fluoropyrimidine, is one of the key drugs for PC in Japan. Phase II studies of S-1 alone as well as those of GS have shown high efficacy against the tumor as the first-line treatment of metastatic PC. Methods: The GEST study was a randomized, prospective, open-label, 3-arm, phase III study. Chemotherapy-naive patients with unresectable advanced PC, an ECOG PS of 0-1, with adequate organ functions were randomly assigned to receive GEM (1000 mg/m2, iv, d1, 8 and 15, q4w), S-1 (80/100/120 mg/day based on BSA, po, d1-28, q6w) or GS (GEM 1000 mg/m2, iv, d1 and 8 plus S-1 60/80/100 mg/day based on BSA po, d1-14, q3w). The primary endpoint was overall survival (OS) to assess the non-inferiority of S-1 alone and the superiority of GS to GEM, with a 90% power and a 1-sided alpha value of 0.0125 for each multiplicity-adjusted comparison. Secondary endpoints were progression-free survival (PFS), response rate (RR), safety, and quality of life (EQ-5D). Results: A total of 834 patients we...

3031 Background: Personalized selection of the right peptides for each patient could be a novel peptide-based immunotherapy for boosting anticancer immunity in many patients (pts). Here we describe immunologic and clinical effects of a personalized peptide vaccine for HLA-A2 positive advanced cancer pts who mostly failed the standard therapy. Methods: To evaluate safety and immune responses of vaccination, 74 HLA-A2 positive advanced cancer pts, including 27 hormone refractory prostate cancer (HRPC), 13 colon cancer (CC), 8 pancreatic cancer (PC), 6 gastric cancer (GC), 4 brain tumor (BT), and 16 other types of cancer (Others) pts were enrolled in a phase I/II clinical trial. Pre-vaccination peripheral blood mononuclear cells and/or plasma were measured for their CTL or IgG levels for each of the 14–20 candidate peptides which can induce HLA-A2-restricted CTL activity against cancer cells followed by weekly or bi-weekly subcutaneous administration of the top four peptides (3mg each) showing the strongest ...

14029 Background: A phase I clinical study was performed to determine safety and immunogenicity of personalized peptide vaccination with gemcitabine (GEM) in advanced pancreatic cancer patients (APC). Methods: Thirteen human histocompatibility leukocyte antigen (HLA)-A24+ or A2+ patients with unresectable (n=10) or recurrent (n=3) pancreatic cancer were treated with GEM plus up to four peptides that were positive for pre-vaccination measurement of peptide-specific IgG antibodies and/or cytotoxic T lymphocyte (CTL) precursors in the circulation (personalized peptide vaccine). GEM was administered at 1000mg/m2 as a 30-min intravenous infusion once a week for three week, followed by 1 week of rest. All patients were treated on outpatient basis. The cycle was repeated every 8 weeks. Results: Peptide doses of vaccination per week were planned as follows: level 1, 1mg; level 2, 2mg; and level 3, 3mg. The main grade 3 toxicities observed during the first cycle in each level were neutropenia (15%), anemia (23%) and thrombocytopenia (15%). No significant differences in the toxicities were found between each level. There was no dose limiting toxicity (DLT) observed in each level. Augmentation of peptide-specific CTL responses in the post-vaccination peripheral blood mononuclear cells was observed in each level, while increased titer of peptide-specific IgG antibodies was observed in the post-vaccination plasma in level 2 and level 3. Applicable responses were no complete response, two partial responses (15%), and 7 stable diseases (55%). Nevertheless 7 patients of them (54%) were under the second-line chemotherapy, disease control rate was 70%, the median TTP (time to progression) was 18.5 weeks and the MST (median survival time) was 7.6 months in this study. Conclusions: The combination therapy of personalized peptide vaccination with GEM for APC patients is feasible and safe. Because of positive immune responses under a full dose of GEM, the peptide vaccination of 3 mg is recommended. No significant financial relationships to disclose.

4097 Background.Pancreatic cancer is one of the cancers with very poor prognosis that might be associated with impaired host immune function. The aim of study is to determine whether circulating de...