Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP-05).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 189-189 ◽  
Author(s):  
Michiaki Unno ◽  
Fuyuhiko Motoi ◽  
Yutaka Matsuyama ◽  
Sohei Satoi ◽  
Ippei Matsumoto ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Adverse Events ◽  
Controlled Trial ◽  
Residual Tumor ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer

189 Background: Despite improvements of postoperative adjuvant therapy for resected pancreatic ductal adenocarcinoma (PDAC), its prognosis remains poor. A randomized controlled trial has begun to compare neoadjuvant chemotherapy using gemcitabine and S1 (NAC-GS) with upfront surgery (Up-S) for patients with PDAC planned resection. Methods: Patients were enrolled after the diagnosis of resectable PDAC with histological confirmation. They were randomly assigned as either NAC-GS or Up-S. In NAC-GS, gemcitabine was provided at a dose of 1 g/m2 on day 1 and 8 and oral S-1 was administered at a dose of 40 mg/m2 twice daily on 1-14 days. Patients received 2 cycles of this regimen. S-1 adjuvant for 6 months was administered for the patients with curative resection and fully recovered within 10 weeks after surgery in both arms. The primary endpoint for the phase III part was overall survival (OS); secondary endpoints included adverse events, resection rate, recurrence-free survival, residual tumor status, nodal metastases, and tumor marker kinetics. The target sample size required 163 patients (α-error 0.05; power 0.8) in each arm. The trial was conducted by the Health Labor Sciences Research Grant (H22-009) of Japan and registered with the UMIN Clinical Trials Registry as UMIN000009634. Results: From January 2013 to January 2016, 364 patients were enrolled in 57 centers (182 to NAC-GS and 182 to Up-S). Of these, two were excluded because of ineligibility, therefore 182 patients in NAC-GS and 180 in Up-S constituted the ITT analysis-set. The median OS was 36.7 months in NAC-GS and 26.6 months in Up-S; HR 0.72 (95% confidential interval 0.55-0.94; p=0.015 [stratified log-rank test]). Grade 3 or 4 adverse events frequently (72.8%) observed in NAC-GS were leukopenia or neutropenia. However, the resection rate, R0 resection rate, and morbidity of the operation were equivalent in the two groups. There was no perioperative mortality in either group. Conclusions: This phase III study demonstrated the significant survival benefits of NAC-GS treatment. Therefore, the results indicated that neoadjuvant chemotherapy could be a new standard for patients with resectable PDAC. Clinical trial information: UMIN000009634.

The effect of neoadjuvant chemotherapy with gemcitabine and S-1 for resectable pancreatic cancer (randomized phase II/III trial; Prep-02/JSAP-05).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4126-4126 ◽  
Author(s):  
Sohei Satoi ◽  
Michiaki Unno ◽  
Fuyuhiko Motoi ◽  
Yutaka Matsuyama ◽  
Ippei Matsumoto ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Adverse Events ◽  
Operation Time ◽  
Ductal Adenocarcinoma ◽  
Perioperative Outcomes ◽  
Rank Test ◽  
Nodal Metastases ◽  
Resection Rate ◽  
Significant Difference

4126 Background: Despite recent progress of adjuvant chemotherapy for resected pancreatic ductal adenocarcinoma (PDAC), its survival remains limited. We conducted a randomized controlled trial to compare neoadjuvant chemotherapy (NAC) with upfront surgery (UP-S) for patients with resectable PDAC. Methods: Patients with resectable PDAC, all confirmed cytologically or histologically were enrolled. Patients received 2 cycles of gemcitabine and S-1 regimen (GS) followed by surgery (NAC) or UP-S after randomization (1:1). Patients in both arms received adjuvant chemotherapy using S-1 for 6 months after surgical resection. The primary endpoint was overall survival (OS); secondary endpoints included adverse events, resection rate, recurrence-free survival, residual tumor status, nodal metastases, and tumor marker kinetics. Results: A total 362 patients were randomly assigned to NAC-GS (n=182) or UP-S (n=180) for 3 years (2013-16). The median OS was 36.7 months in NAC-GS and 26.6 months in UP-S; HR 0.72 (p=0.015, stratified log-rank test) at 2.5 year after final enrollment. Crude resection rate for NAC and UP-S were 77%, 72% respectively. There was no operative mortality in both groups. Although G3/4 adverse events were observed frequently (73%) during NAC, no significant difference for both groups was observed for perioperative outcomes including blood loss, operation time, R0 resection rate and post-operative morbidity. Significant decrease of pathological nodal metastases in NAC was noted compared to those in UP-S by pathological evaluation for resected patients(p<0.01). Although significant decrease of viable tumor cells was observed in primary tumor after NAC compared to UP-S (p<0.01), Evans IIb or more was found in only 14 % of resected patients in NAC. Hepatic recurrence after surgery was significantly reduced in NAC (30.0%) compared to UP-S (47.5%) in observed period. Conclusions: The strategy of NAC showed significant longer survival compared to that of UP-S with acceptable feasibility. The effect of NAC might imply the control of subdiagnostic liver metastases before surgery for resectable PDAC. Clinical trial information: UMIN000009634.

scholarly journals Neoadjuvant Chemotherapy Compared With Surgery Alone for Locally Advanced Cancer of the Stomach and Cardia: European Organisation for Research and Treatment of Cancer Randomized Trial 40954

2010 ◽  
Vol 28 (35) ◽  
pp. 5210-5218 ◽  
Author(s):  
Christoph Schuhmacher ◽  
Stephan Gretschel ◽  
Florian Lordick ◽  
Peter Reichardt ◽  
Werner Hohenberger ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Lymph Node ◽  
Neoadjuvant Chemotherapy ◽  
Preoperative Chemotherapy ◽  
Survival Benefit ◽  
Locally Advanced ◽  
Postoperative Chemotherapy ◽  
Phase Iii ◽  
R0 Resection ◽  
Resection Rate

PurposePatients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy, although fewer than 50% could receive postoperative chemotherapy. We examined the value of purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines.Patients and MethodsPatients with locally advanced adenocarcinoma of the stomach or esophagogastric junction (AEG II and III) were randomly assigned to preoperative chemotherapy followed by surgery or to surgery alone. To detect with 80% power an improvement in median survival from 17 months with surgery alone to 24 months with neoadjuvant, 282 events were required.ResultsThis trial was stopped for poor accrual after 144 patients were randomly assigned (72:72); 52.8% patients had tumors located in the proximal third of the stomach, including AEG type II and III. The International Union Against Cancer R0 resection rate was 81.9% after neoadjuvant chemotherapy as compared with 66.7% with surgery alone (P = .036). The surgery-only group had more lymph node metastases than the neoadjuvant group (76.5% v 61.4%; P = .018). Postoperative complications were more frequent in the neoadjuvant arm (27.1% v 16.2%; P = .09). After a median follow-up of 4.4 years and 67 deaths, a survival benefit could not be shown (hazard ratio, 0.84; 95% CI, 0.52 to 1.35; P = .466).ConclusionThis trial showed a significantly increased R0 resection rate but failed to demonstrate a survival benefit. Possible explanations are low statistical power, a high rate of proximal gastric cancer including AEG and/or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area (celiac trunc, hepatic ligament, lymph node at a. lienalis; D2).

Phase II trial of neoadjuvant S-1 and concurrent radiotherapy for borderline resectable pancreatic cancer: Interim results of JASPAC05.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4107-4107 ◽  
Author(s):  
Shinichiro Takahashi ◽  
Izumi Ohno ◽  
Masafumi Ikeda ◽  
Masaru Konishi ◽  
Tatsushi Kobayashi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Primary Endpoint ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Concurrent Radiotherapy

4107 Background: Borderline resectable pancreatic cancer (BRPC) has a high probability of a positive surgical margin and poor prognosis because the tumor interacts with surrounding arteries or veins. Chemoradiotherapy (CRT) with S-1 has shown favorable activity in locally advanced pancreatic cancer. This study was designed to assess S-1 and concurrent radiotherapy in a neoadjuvant setting to determine whether it increases R0 resection rate for BRPC. Methods: This was a multicenter, single-arm phase II study. Patients with BRPC received S-1 (40 mg/m2 BID) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery if they fulfilled any of the following: (1) bilateral impingement of superior mesenteric vein or portal vein; (2) tumor contact with superior mesenteric artery ≤180°; or (3) tumor contact with common hepatic artery or celiac axis ≤180°. Primary endpoint was R0 resection rate in BRPC confirmed by central review. At least 40 patients were required, with one-sided α = 0.05 and β = 0.05, with an expected and a threshold values for primary endpoint of 30% and 10%. Results: Fifty-two patients were eligible between December 2012 and May 2016. CRT was completed in 50 patients (96%) and was safe, with mostly grade 1 or 2 adverse events. Protocol treatment was withdrawn before surgery in 12 patients because of progressive disease diagnosed by computed tomography, and in one because of treatment refusal. Ten patients received exploratory laparotomy, or palliative/noncurative resection. In the rest of 29, R0 resection was conducted in 27, and R1 and RX in 1 patient each. This gave an R0 resection rate of 52% in all 52 eligible patients. In the 41 cases of BRPC confirmed by central review, R0 was confirmed in 26 (63%). Destruction of > 50% of tumor cells was confirmed pathologically in 10 (32%). Postoperative grade III/IV adverse events according to Clavien–Dindo classification were observed in 6 (15%). Conclusions: S-1 and concurrent radiotherapy were well tolerated and found to be effective in BRPC. A randomized controlled trial comparing neoadjuvant CRT and chemotherapy, including gemcitabine+nab-paclitaxel, for BRPC is under planning. Clinical trial information: NCT02459652.

Alliance for clinical trials in oncology trial A021501: Preoperative extended chemotherapy vs. chemotherapy plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the head of the pancreas.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4151-TPS4151 ◽  
Author(s):  
Matthew H. G. Katz ◽  
Fang-Shu Ou ◽  
Joseph Herman ◽  
Syed A. Ahmad ◽  
Brian M. Wolpin ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Radiation Therapy ◽  
De Novo ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
R0 Resection ◽  
Preoperative Treatment ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Oncology Trial

TPS4151 Background: Borderline resectable pancreatic cancers infiltrate into adjacent vascular structures to an extent that makes an R0 resection unlikely when pancreatectomy is performed de novo. In a pilot study, Alliance for Clinical Trials in Oncology Trial A021101, the median survival of patients who received chemotherapy and radiation prior to anticipated pancreatectomy was 22 months, and an R0 resection was achieved in 64% of operations. However, the individual contributions of preoperative chemotherapy and radiation therapy are poorly defined.This study, Alliance for Clinical Oncology Trial A021501, will help define a standard preoperative treatment regimen for borderline resectable pancreatic cancer and position the superior arm for further evaluation in future phase III trials. Methods: In this recently activated randomized phase II trial, 134 patients with a biopsy-confirmed pancreatic ductal adenocarcinoma that meets centrally-reviewed radiographic criteria for borderline resectable disease are randomized to receive either 8 cycles of modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2 and infusional 5-fluorouracil 2400 mg/m2 for 4 cycles) or to 7 cycles of modified FOLFIRINOX followed by stereotactic body radiation therapy (33-40 Gy in 5 fractions). Patients without evidence of disease progression following preoperative therapy undergo pancreatectomy and subsequently receive 4 cycles of postoperative modified FOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and infusional 5-fluorouracil 2400 mg/m2 for 4 cycles). The primary endpoint is the 18-month overall survival rate of patients enrolled into each of the two treatment arms. An interim analysis of the R0 resection rate within each arm will be conducted to assess treatment futility after accrual of 30 patients. Secondary endpoints include rates of margin-negative resection and event-free survival. The trial is activated nationwide and eligible to be opened for accrual at any National Clinical Trials Network cooperative group member site. Clinical trial information: NCT02839343.

Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1): A randomized, controlled, multicenter phase III trial.

2018 ◽  
Vol 36 (18_suppl) ◽  
pp. LBA4002-LBA4002 ◽  
Author(s):  
Geertjan Van Tienhoven ◽  
Eva Versteijne ◽  
Mustafa Suker ◽  
Karin B.C. Groothuis ◽  
Olivier R. Busch ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Phase Iii ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Randomized Controlled ◽  
Immediate Surgery

LBA4002 Background: Standard of care for patients with (borderline) resectable pancreatic adenocarcinoma is resection followed by adjuvant chemotherapy. Previous studies suggest a benefit of neoadjuvant treatment. We conducted a multicenter phase III randomized controlled trial to evaluate the effect of preoperative chemoradiotherapy. Methods: Patients with (borderline) resectable pancreatic cancer, pathologically confirmed, were randomized between immediate surgery (arm A) and preoperative chemoradiotherapy (arm B), both followed by adjuvant chemotherapy. The preoperative chemoradiotherapy consisted of 15 times of 2.4 Gray (Gy) combined with gemcitabine, 1,000 mg/m2 on days 1, 8 and 15, preceded and followed by a cycle of gemcitabine. Primary endpoint was overall survival (OS), secondary endpoints were (R0) resection rate, disease free survival (DFS), distant metastases free interval (DMFI), locoregional recurrence free interval (LRFI) and toxicity. Accrual was completed between April 23, 2013 and July 25, 2017. Results: In total, 246 patients were included in the intention-to-treat analysis (127 patients in arm A and 119 in arm B). Currently, 142 of the 176 needed events for the primary outcome are observed. OS was significantly better in arm B (median 13.5 vs. 17.1 months; HR 0.71; p = 0.047). This was also the case for R0 resection rate (31% vs. 65%, p = < 0.001), DFS (median 7.9 vs. 11.2 months; HR 0.67; p = 0.010), DMFI (median 10.2 vs 17.1 months; HR 0.63; p = 0.012) and LRFI (median 11.8 vs not reached; HR 0.47; p < 0.001). Resection rates were 72% (91/127) in arm A vs. 62% (74/119) in arm B (p = 0.15). No significant difference was observed in grade ≥ 3 adverse events between both groups (p = 0.17). A subgroup analysis of patients who actually underwent a resection was performed which showed a median OS of 16.8 and 29.9 months respectively (p < 0.001). Conclusion: Our preliminary data show that preoperative chemoradiotherapy significantly improves outcome in (borderline) resectable pancreatic cancer compared to immediate surgery. Updated results will be presented at the meeting. Clinical trial information: NTR3709.

Extensive peritoneal lavage after curative gastrectomy for gastric cancer study (EXPEL): An international multicenter randomized controlled trial.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 279-279 ◽  
Author(s):  
Jimmy Bok Yan So ◽  
Jiafu Ji ◽  
Sang Uk Han ◽  
Masanori Terashima ◽  
Guoxin Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Cumulative Incidence ◽  
Peritoneal Lavage ◽  
Controlled Trial ◽  
Peritoneal Recurrence ◽  
Phase Iii ◽  
Rank Test ◽  
Curative Gastrectomy ◽  
Multicenter Randomized Controlled Trial

279 Background: Peritoneal recurrence of gastric cancer after curative surgical resection is common and portends a poor prognosis. Preliminary studies suggest extensive intraoperative peritoneal lavage (EIPL) may reduce the risk of peritoneal recurrence and improve survival. We sought to perform a randomized phase III study to definitively establish the role of performing EIPL after gastrectomy. Methods: This is a prospective, open-label, phase 3 multicentre randomised controlled trial involving 22 hospitals from Korea. China, Japan, Malaysia and Singapore. Patients aged between 21 to 80 years with cT3/4 stomach cancer undergoing curative resection were randomized to either surgery and EIPL (lavage with 10 litres of saline) or surgery alone. Comparison of DFS and OS were made via log-rank test. The cumulative incidence of peritoneal recurrence was compared using competing risks approach. All analyses were performed based on intention-to-treat. Results: Between March 2015 to August 2018, 800 patients were randomly assigned to surgery alone ( n= 402) or EIPL ( n= 398). Based on a median follow-up duration of 29 months, the 3-year cumulative incidence of all-cause mortality was 23.1% and 23.3% for EIPL and surgery alone respectively (hazard ratio [HR] = 1.09, 95% CI: 0.78 to 1.52, p = 0.615). Similarly, the 3-year cumulative incidence of recurrence were 28.0% and 25.9% respectively (HR = 1.01, 95% CI: 0.74 to 1.37, p = 0.947), and 7.9% and 6.6% respectively for peritoneal recurrence (Subdistribution HR = 1.33, 95% CI: 0.73 to 2.42, p = 0.347). Overall, the risk of adverse events was higher in EIPL as compared to surgery alone (relative risk = 1.58, 95% CI 1.07 to 2.33, p = 0.019). The most common adverse events were anastomotic leak, bleeding and intra-abdominal abscess. At the planned third interim analysis on 28 August 2019, the predictive probability of achieving even a 5% difference in 3-year OS in favour of EIPL at final analysis was < 0.4%. The trial was thus recommended to terminate on the basis of futility. Conclusions: EIPL does not show any survival benefit compared with surgery alone and is not recommended for patients undergoing curative gastrectomy for cancer. Clinical trial information: NCT02140034.

ESPAC-4: A multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy of gemcitabine (GEM) and capecitabine (CAP) versus monotherapy gemcitabine in patients with resected pancreatic ductal adenocarcinoma.

2016 ◽  
Vol 34 (18_suppl) ◽  
pp. LBA4006-LBA4006 ◽  
Author(s):  
John P. Neoptolemos ◽  
Dan Palmer ◽  
Paula Ghaneh ◽  
Juan W. Valle ◽  
David Cunningham ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Combination Chemotherapy ◽  
Performance Status ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Full Analysis ◽  
Grade 3

LBA4006 Background: The ESPAC-3 trial compared adjuvant GEM with 5-fluorouracil/folinic acid for resected pancreatic cancer. GEM is the standard of care based on similar survival and less toxicity. ESPAC-4 aimed to determine whether combination chemotherapy with GEM/CAP improved survival compared to GEM monotherapy. Methods: Patients with pancreatic ductal adenocarcinoma were randomized within 12 weeks of surgery (stratified for R0/R1 resection margin status and country) to have either six 4 week cycles of IV GEM alone or GEM with oral CAP. The primary endpoint was overall survival; secondary endpoints were toxicity, relapse free survival, 2 and 5 year survival and quality of life. 722 patients (480 expected events), 361 in each arm, were needed to detect a 10% difference in 2 year survival rates with 90% power (log-rank test with 5% two-sided alpha). Results: Between Nov 10 2008 and Sep 11 2014, 732 patients were randomized with 730 included in the full analysis set (366 GEM, 364 GEM/CAP). Median age was 65 years, 57% were men. WHO performance status was 0, 1 or 2 in 42% 55% and 3% respectively. Postoperative median CA19-9 was 19 kU/L. Median maximum tumor size was 30 mm, 60% were R1 resections, 80% were node positive and 40% were poorly differentiated. On Dec 11 2015 the Independent Trial Steering Committee requested that the trial proceed to full analysis. The data freeze was on March 2 2016. Median survival (months) for patients treated with GEM/CAP was 28.0 (95% CI, 23.5 – 31.5) and 25.5 (22.7 – 27.9) for GEM. Stratified log-rank analysis revealed an HR=0.82 [95% CI, 0.68 – 0.98]; χ2 (1) = 4.61, P=0.032. 196 out of 366 GEM patients in the safety set reported 481 grade 3/4 adverse events, while 226 out of 359 GEM/CAP patients reported 608 grade 3/4 adverse events ( P=0.242). Conclusions: Adjuvant GEM/CAP for pancreatic cancer had a statistically significant improvement in survival compared to GEM monotherapy. Clinical trial information: ISRCTN96397434.

scholarly journals Total neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2 trial): study protocol for a nationwide multicenter randomized controlled trial

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Q. P. Janssen ◽  
◽  
J. L. van Dam ◽  
B. A. Bonsing ◽  
H. Bos ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Venous Involvement ◽  
Randomized Controlled

Abstract Background Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including single-agent chemotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer patients. Methods This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤ 90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤ 270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients assuming an accrual period of 3 years and 1.5 years follow-up. Discussion The PREOPANC-2 trial directly compares two neoadjuvant regimens for patients with resectable and borderline resectable pancreatic cancer. Our study will provide evidence on the neoadjuvant treatment of choice for patients with resectable and borderline resectable pancreatic cancer. Trial registration Primary registry and trial identifying number: EudraCT: 2017–002036-17. Date of registration: March 6, 2018. Secondary identifying numbers: The Netherlands National Trial Register – NL7094, NL61961.078.17, MEC-2018-004.

Total neoadjuvant FOLFIRINOX or gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2): A nationwide multicenter randomized controlled trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4171-TPS4171
Author(s):  
Quisette Janssen ◽  
Jacob L. van Dam ◽  
Marc G.H. Besselink ◽  
Marjolein Y.V. Homs ◽  
Geertjan van Tienhoven ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Venous Involvement ◽  
Randomized Controlled

TPS4171 Background: Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials (including the Dutch PREOPANC trial) have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including gemcitabine-based chemoradiotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether total neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine (i.e. the intervention arm of the PREOPANC trial) in patients with resectable or borderline resectable pancreatic cancer. Methods: This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) added during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients, assuming an accrual period of 3 years and 1.5 years follow-up. Between June 2018 and January 2021, 375 patients were enrolled in 20 centers in the Netherlands and accrual is complete. Final analyses are expected at the end of 2022. Netherlands Trial Register: NL7094. Clinical trial information: NL7094.

ESPAC-4: A multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy of gemcitabine (GEM) and capecitabine (CAP) versus monotherapy gemcitabine in patients with resected pancreatic ductal adenocarcinoma: Five year follow-up.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4516-4516
Author(s):  
John P. Neoptolemos ◽  
Daniel H. Palmer ◽  
Paula Ghaneh ◽  
Juan W. Valle ◽  
David Cunningham ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Survival Rates ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Serious Adverse Events ◽  
Grade 3

4516 Background: The ESPAC-4 trial demonstrated that adjuvant GEM/CAP for pancreatic cancer significantly improved survival compared to GEM monotherapy. The aim of this study is to evaluate the long-term outcomes in the ESPAC-4 trial. Methods: Patients with pancreatic ductal adenocarcinoma were randomized within 12 weeks of surgery (stratified for R0/R1 resection margin status and country) to have either six 4-week cycles of IV GEM alone or GEM with oral CAP. The primary endpoint was five-year survival; secondary endpoints were toxicity and relapse free survival. 722 patients (480 expected events), 361 in each arm, were needed to detect a 10% difference in 2-year survival rates with 90% power (log-rank test with 5% two-sided alpha). Results: Between Nov 10 2008 and Sep 11 2014, 732 patients were randomized with 730 included in the full analysis set (366 GEM, 364 GEM/CAP). Median age was 65 years, 57% were men. WHO performance status was 0, 1 or 2 in 42% 55% and 3% respectively. Postoperative median CA19-9 was 19 kU/L. Median maximum tumor size was 30 mm, 61% were R1 resections, 80% were node positive and 40% were poorly differentiated. The data freeze was on 24 February 2020; median follow up was 60 months with 531 overall deaths, 280 in GEM, and 251 in GEM/CAP. Median (95% CI) survival (months) for patients treated with GEM/CAP was 27.7 23.3 – 31.2) and 26.0 (22.7 – 28.4) for GEM. Five-year (95% CI) survival rates were 20 (16 – 25) % for GEM and 28 (23 – 33) % for GEM/CAP. Stratified log-rank analysis revealed an HR=0.84 [95% CI, 0.70 – 0.99]; χ2 (1) = 3.87, P=0.049. 70 out of 366 GEM patients in the safety set reported 101 grade 3/4 serious adverse events, while 65 out of 359 GEM/CAP patients reported 97 grade 3/4 serious adverse events ( P=0.724). Conclusions: Adjuvant GEM/CAP for pancreatic cancer had a statistically significant improvement in survival compared to GEM monotherapy. Clinical trial information: 96397434 .

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