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

Abstract

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.

Postoperative venous thromboembolism and mortality in patients with pancreatic surgery

“…Additional subanalysis demonstrated increased mortality in patients who did not receive preoperative chemotherapy. This finding is consistent with the preliminary result of the recent phase III PREOPANC‐1 trial that preoperative treatment improves outcomes in resectable pancreatic cancer …”

Short‐term outcomes after vascular resection for pancreatic tumors: Lessons learned from 72 cases from a single Brazilian Cancer Center

“…It demonstrated prolonged rates of OS, disease‐free survival, distant metastasis‐free survival, locoregional relapse‐free survival, and R0 resection rates. The PRODIGE 24 study achieved median OS rates of 54.4 months with modified adjuvant FOLFIRINOX in selected patients after excellent surgical recovery …”

Neoadjuvant treatment for resectable pancreatic adenocarcinoma: What is the best protocol?

“…Van Tienhoven et al conducted an RCT of NACRT for R and BR PDAC (PREOPANC‐1 trial). Their preliminary results showed an improved trend in OS by NACRT, but it was not significant . Several secondary endpoints were shown to be in favour of NACRT, including the R0 resection rate and disease‐free survival.…”

“…The reduction of hepatic relapse after surgery with NAC might suggest that pre‐operative systemic delivery of combination chemotherapy would be necessary to impede the progression of micrometastases even in R PDAC, providing long‐term survival. The low resection rate of NACRT might be partly because previous studies used a reduced dose of systemic chemotherapy in combination with radiotherapy. Katz et al reported the feasibility and efficacy of NAC FOLFIRINOX followed by NACRT for BR PDAC in multi‐institutional trials.…”