Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial

Labori, Knut Jørgen; Bratlie, Svein Olav; Andersson, Bodil; Angelsen, Jon-Helge; Biörserud, Christina; Björnsson, Bergthor; Bringeland, Erling Audun; Elander, Nils; Garresori, Herish; Grønbech, Jon Erik; Haux, Johan; Hemmingsson, Oskar; Liljefors, Maria Gustafsson; Myklebust, Tor Åge; Nymo, Linn Såve; Peltola, Katriina; Pfeiffer, Per; Sallinen, Ville; Sandström, Per; Sparrelid, Ernesto; Stenvold, Helge; Søreide, Kjetil; Tingstedt, Bobby; Verbeke, Caroline; Öhlund, Daniel; Klint, Leif; Dueland, Svein; Lassen, Kristoffer; Aahlin, Eirik Kjus; Bratthäll, Charlotte; Halimi, Asif; Hatlevoll, Ingunn; Heby, Margareta; Kokkola, Arto; Kordes, Maximilian; Lindblad, Stina; Lundgren, Linda; Mortensen, Michael Bau; Mortensen, Kim Erlend; Persson, Jan; Rangelova, Elena; Rønne, Elin; Sandvik, Oddvar Mathias; Søreide, Jon Arne; Vilhav, Caroline; Waardal, Kim; Wennerblom, Johanna; Williamsson, Caroline; Yaqub, Sheraz

doi:10.1016/s2468-1253(23)00405-3

Cited by 52 publications

(13 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Table 3 presents the results of major previous RCTs and our research. 2 , 3 , 11 , 13 , 17 , 19 , 26 – 31 In the NEONAX and SWOG-1505 trials, 19 , 30 six cycles of GA regimen treatment were divided into NAC and AC and administered to patients with R-PDAC, referring to the APACT trial. 11 Both clinical trials with the NAC-GA arm demonstrated modest clinical benefits (OS/PFS/resection rate, 24–26 months/12 months/70%).…”

Section: Discussionmentioning

confidence: 99%

Results of a Randomized Clinical Study of Gemcitabine Plus Nab-Paclitaxel Versus Gemcitabine Plus S-1 as Neoadjuvant Chemotherapy for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma (RCT, CSGO-HBP-015)

Yamada,

Kobayashi,

Takahashi

et al. 2024

Ann Surg Oncol

View full text Add to dashboard Cite

Background The optimal neoadjuvant chemotherapy (NAC) regimen for patients with localized pancreatic ductal adenocarcinoma (PDAC) remains uncertain. This trial aimed to evaluate the efficacy and safety of two neoadjuvant chemotherapy (NAC) regimens, gemcitabine plus nab-paclitaxel (GA) and gemcitabine plus S-1 (GS), in patients with resectable/borderline-resectable (R/BR) PDAC. Patients and Methods Treatment-naïve patients with R/BR-PDAC were enrolled and randomly allocated. They received two cycles (2 months) of each standard protocol, followed by radical surgery for those without tumor progression in general hospitals belonging to our intergroup. The primary endpoint was to determine the superior regimen on the basis of achieving a 10% increase in the rate of patients with progression-free survival (PFS) at 2 years from allocation. Results A total of 100 patients were enrolled, with 94 patients randomly assigned to the GS arm (N = 46) or GA arm (N = 48). The 2-year PFS rates did not show the stipulated difference [GA, 31% (24–38%)/GS, 26% (18–33%)], but the Kaplan–Myer analysis showed significance (median PFS, GA/GS 14 months/9 months, P = 0.048; HR 0.71). Secondary endpoint comparisons yielded the following results (GA/GS arm, P-value): rates of severe adverse events during NAC, 73%/78%, P = 0.55; completion rates of the stipulated NAC, 92%/83%, P = 0.71; resection rates, 85%/72%, P = 0.10; average tumor marker (CA19-9) reduction rates, −50%/−21%, P = 0.01; average numbers of lymph node metastasis, 1.7/3.2, P = 0.04; and median overall survival times, 42/22 months, P = 0.26. Conclusions This study found that GA and GS are viable neoadjuvant treatment regimens in R/BR-PDAC. Although the GA group exhibited a favorable PFS outcome, the primary endpoint was not achieved.

show abstract

Section: Discussionmentioning

confidence: 99%

Results of a Randomized Clinical Study of Gemcitabine Plus Nab-Paclitaxel Versus Gemcitabine Plus S-1 as Neoadjuvant Chemotherapy for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma (RCT, CSGO-HBP-015)

Yamada,

Kobayashi,

Takahashi

et al. 2024

Ann Surg Oncol

View full text Add to dashboard Cite

show abstract

“…To date, nine studies have been conducted on resectable PC (Table 1) [24][25][26][27][28][29][30][31][32]. Palmer et al explored the efficacy of gemcitabine (GEM) + cisplatin (n = 26) with respect to that of GEM alone (n = 24) in a neoadjuvant setting [27].…”

Section: Randomized Phase II and Iii Trials On Resectable Pcmentioning

confidence: 99%

“…PACT-15 was the first multicenter, openlabel, Phase II RCT from Italy on resectable PC (n = 88 patients); it revealed that the PEXG regimen (comprising cisplatin, epirubicin, GEM, and capecitabine) extended the median OS to 38.2 months, thereby validating the usefulness of NAT for resectable PC [28]. Two RCTs and one randomized Phase II trial have been conducted to evaluate the utility and safety of NAT in comparison with those of upfront surgery [26,[31][32][33]. The PREOPANC-1 study from the Netherlands revealed that despite a small difference in the MST between the NAT and upfront surgery groups, the OS was better in the NAT group than in the upfront surgery group (17.4 vs. 14.4 months, p = 0.025) [32,33].…”

Section: Randomized Phase II and Iii Trials On Resectable Pcmentioning

confidence: 99%

“…Similarly, the PREP2/JSAP5 study in Japan revealed that, compared with upfront surgery, NAT led to better OS (26.6 vs. 36.7 months, p = 0.015) [31]. However, the most recent international randomized Phase II trial, NORPACT-1, did not demonstrate a survival benefit of neoadjuvant FOLFIRINOX when compared with upfront surgery (OS: 25.1 vs. 38.5 months, p = 0.05) [26]. Several randomized Phase II trials have been conducted recently to elucidate the optimal NAT regimens for cohorts with resectable PC [29,30,34].…”

Section: Randomized Phase II and Iii Trials On Resectable Pcmentioning

confidence: 99%

See 1 more Smart Citation

Evidence and Future Perspectives for Neoadjuvant Therapy for Resectable and Borderline Resectable Pancreatic Cancer: A Scoping Review

Endo,

Kitago,

Kitagawa

2024

Cancers

View full text Add to dashboard Cite

Pancreatic cancer (PC) is a lethal disease that requires innovative therapeutic approaches to enhance the survival outcomes. Neoadjuvant treatment (NAT) has gained attention for resectable and borderline resectable PC, offering improved resection rates and enabling early intervention and patient selection. Several retrospective studies have validated its efficacy. However, previous studies have lacked intention-to-treat analyses and appropriate resectability classifications. Randomized comparative trials may help to enhance the clinical applicability of evidence. Therefore, after searching the MEDLINE database, this scoping review presents a comprehensive summary of the evidence from published (n = 14) and ongoing (n = 12) randomized Phase II and III trials. Diverse regimens and their outcomes were explored for both resectable and borderline resectable PC. While some trials have supported the efficacy of NAT, others have demonstrated no clear survival benefits for patients with resectable PC. The utility of NAT has been confirmed in patients with borderline resectable PC, but the optimal regimens remain debatable. Ongoing trials are investigating novel regimens, including immunotherapy, thereby highlighting the dynamic landscape of PC treatment. Studies should focus on biomarker identification, which may enable precision in oncology. Future endeavors aim to refine treatment strategies, guided by precision oncology.

show abstract

“…However, conflicting evidence showed no clear improvement in survival, and more data on this issue is needed before issuing favorable recommendations for clinical practice [98] , [99] . More recently, a randomised clinical trial found no survival benefit from the use of neoadjuvant therapy in resectable patients with PDAC, when compared to upfront resection, further disfavoring its use [100] .…”

Section: Staging Of Pdacmentioning

confidence: 99%

Imaging of pancreatic ductal adenocarcinoma – An update for all stages of patient management

Bilreiro,

Andrade,

Santiago

et al. 2024

European Journal of Radiology Open

View full text Add to dashboard Cite

Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial

Cited by 52 publications

References 27 publications

Results of a Randomized Clinical Study of Gemcitabine Plus Nab-Paclitaxel Versus Gemcitabine Plus S-1 as Neoadjuvant Chemotherapy for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma (RCT, CSGO-HBP-015)

Results of a Randomized Clinical Study of Gemcitabine Plus Nab-Paclitaxel Versus Gemcitabine Plus S-1 as Neoadjuvant Chemotherapy for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma (RCT, CSGO-HBP-015)

Evidence and Future Perspectives for Neoadjuvant Therapy for Resectable and Borderline Resectable Pancreatic Cancer: A Scoping Review

Imaging of pancreatic ductal adenocarcinoma – An update for all stages of patient management

Contact Info

Product

Resources

About