ESPAC-5F: Four arm, international randomised phase II trial of immediate surgery compared with neoadjuvant gemcitabine plus capecitabine (GEMCAP) or FOLFIRINOX or chemoradiotherapy (CRT) in patients with borderline resectable pancreatic cancer

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 Protocol treatment was withdrawn before surgery in 12 patients because of progressive disease diagnosed by computed tomography, and in one because of treatment refusal.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.

Download Full-text

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

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.18_suppl.lba4002 ◽

2018 ◽

Vol 36 (18_suppl) ◽

pp. LBA4002-LBA4002 ◽

Cited By ~ 83

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.

Download Full-text

Final results of JASPAC05: Phase II trial of neoadjuvant S-1 and concurrent radiotherapy followed by surgery in borderline resectable pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.4127 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 4127-4127 ◽

Cited By ~ 2

Author(s):

Shinichiro Takahashi ◽

Izumi Ohno ◽

Masafumi Ikeda ◽

Masaru Konishi ◽

Tatsushi Kobayashi ◽

...

Keyword(s):

Pancreatic Cancer ◽

Phase Ii ◽

Primary Endpoint ◽

Response Rate ◽

R0 Resection ◽

Resection Rate ◽

Resectable Pancreatic Cancer ◽

Borderline Resectable ◽

Borderline Resectable Pancreatic Cancer ◽

Concurrent Radiotherapy

4127 Background: Borderline resectable pancreatic cancer (BRPC) is frequently associated with positive surgical margins and a poor prognosis when treated with upfront surgery. This study was designed to assess whether neoadjuvant chemoradiotherapy (CRT) with S-1 increases the R0 resection rate. 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 the superior mesenteric vein or portal vein; and (2) tumor contact ≤180° with the superior mesenteric artery, common hepatic artery, or celiac axis. The primary endpoint was the R0 resection rate in BRPC confirmed by central review. Secondary endpoints were overall survival (OS), progression-free survival (PFS), response rate (RECISTv1.1), pathological response rate, surgical morbidity (Clavien–Dindo classification), and toxicity (CTCAEv4.0). At least 40 patients were required, with one-sided α = 0.05 and β = 0.05, with an expected and threshold value for the primary endpoint of 30% and 10%. Results: Fifty-two patients were eligible, of whom 41 had BRPC by central review. CRT was completed in 50 (96%) patients and was well tolerated. The rate of grade 3/4 toxicity with CRT was 43%. The R0 resection rate was 52% (95% CI, 37.6%–66.0%) in 52 eligible patients and 63% (95% CI, 46.9%–77.9%) in 41 patients with BRPC. The radiological response rate was 5.8%, while destruction of > 50% of tumor cells was shown microscopically in 32% of patients. Postoperative grade III/IV adverse events were observed in 7.5% of operated patients. Among the 52 eligible patients, the 2-year OS rate, median OS, and median PFS were 51%, 25.8 mo, and 6.7 mo. Of the 41 patients with BRPC, the 2-year OS rate, median OS, and median PFS were 58%, 30.8 mo, and 10.4 mo. Conclusions: S-1 and concurrent radiotherapy appear to be feasible and effective at increasing the R0 resection rate with encouraging survival rates in BRPC. A phase II/III trial evaluating this treatment is ongoing. Clinical trial information: NCT02459652.

Download Full-text