A Phase II Clinical Trial of Molecular Profiled Neoadjuvant Therapy for Localized Pancreatic Ductal Adenocarcinoma

Abstract

We report the first prospective clinical trial that utilized molecular profiling to select neoadjuvant therapy in patients with operable PDAC. Such high resectability rates have not been observed in prior neoadjuvant trials, suggesting that molecular profiling may improve the efficacy of chemotherapy in these patients.

Impact of Neoadjuvant Chemoradiation on Pathologic Response in Patients With Localized Pancreatic Cancer

“…Regional nodal radiation was routinely included and typically involved the proximal celiac and superior mesenteric (artery and vein) vessels, along with the splenic or porta hepatis nodes depending on primary tumor location. A subset of patients with resectable PC received 2 months of chemotherapy on a clinical trial utilizing molecular profiling (16). For patients with BLR PC, neoadjuvant therapy consisted of a minimum of 2 months of chemotherapy followed by chemoradiation (50.4 Gy over 28 fractions).…”

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

“…18,19 Landry et al 20 These results are summarized in Table 1. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] Although these studies reported the survival outcome of an ITT cohort, none of them had a cohort treated by upfront surgery as a control. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] Several meta-analyses investigated the efficacy of neoadjuvant.…”

“…36,37,[41][42][43][44] Considering recent progress in chemotherapy for UR PDAC, 45,46 a clinical question has been raised about the optimal protocol in the neoadjuvant setting. 24 Okano K 57 R, BR S1 + RT 91% N. R. N. R. 25 Motoi F 101 R, BR GEM/S1 73% 30.8 N. R. 26 Tsai S 130 R, BR FOLFIRINOX (n = 52) FOLFIRI (n = 26) GEM/Nab-P (n = 16) CAP/Nab-P (n = 15) *+RT (n = 83) 82% 38 45 27 Eguchi H 63 R GEM/S1 + RT 86% 55.3 NR 39,40 showed a significantly higher response rate and longer PFS than gemcitabine single-agent. 47 Ozaka et al 48 also reported similar results, with a high response rate and longer PFS, in a randomized, phase II trial.…”

“…Many prospective non-randomized trials of NACRT have been reported. 14,15,[18][19][20][21][22]25,27,28 RCTs comparing NACRT with upfront surgery, however, have not yet been fully reported, [33][34][35][36][37] in contrast to NAC. [38][39][40] The good survival outcomes.…”

Biochemical Predictors of Response to Neoadjuvant Therapy in Pancreatic Ductal Adenocarcinoma

“…Using a panel of 6 protein biomarkers to guide gemcitabine or 5-FU based chemotherapeutic selection, the authors increased rates of treatment completion (neoadjuvant and resection) from 50 to 70% in borderline resectable PDAC cases, and from 80 to 90% in resectable cases. These improvements translated to overall survivals (OS) of 38 months in all patients and 45 months in patients who completed treatment, both an improvement over historical controls (4).…”