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Clinical Trial
. 2024 Jun;31(6):4073-4083.
doi: 10.1245/s10434-024-15011-7. Epub 2024 Mar 8.

Adjuvant Gemcitabine Versus Neoadjuvant/Adjuvant FOLFIRINOX in Resectable Pancreatic Cancer: The Randomized Multicenter Phase II NEPAFOX Trial

Thorsten O Goetze  1   2   3 , Alexander Reichart  4 , Ulli S Bankstahl  4 , Claudia Pauligk  5 , Maria Loose  5 , Thomas W Kraus  6 , Moustafa Elshafei  6 , Wolf O Bechstein  7 , Jörg Trojan  8 , Matthias Behrend  9 , Nils Homann  10 , Marino Venerito  11 , Wolfram Bohle  12   13 , Michael Varvenne  14 , Claus Bolling  15 , Dirk M Behringer  16 , Karsten Kratz-Albers  17 , Gabriele M Siegler  18 , Wael Hozaeel  4 , Salah-Eddin Al-Batran  4   19   5
Affiliations
Clinical Trial

Adjuvant Gemcitabine Versus Neoadjuvant/Adjuvant FOLFIRINOX in Resectable Pancreatic Cancer: The Randomized Multicenter Phase II NEPAFOX Trial

Thorsten O Goetze et al. Ann Surg Oncol. 2024 Jun.

Abstract

Background: Although addition of adjuvant chemotherapy is the current standard, the prognosis of pancreatic cancers still remains poor. The NEPAFOX trial evaluated perioperative treatment with FOLFIRINOX in resectable pancreatic cancer.

Patients and methods: This multicenter phase II trial randomized patients with resectable or borderline resectable pancreatic cancer without metastases into arm (A,) upfront surgery plus adjuvant gemcitabine, or arm (B,) perioperative FOLFIRINOX. The primary endpoint was overall survival (OS).

Results: Owing to poor accrual, recruitment was prematurely stopped after randomization of 40 of the planned 126 patients (A: 21, B: 19). Overall, approximately three-quarters were classified as primarily resectable (A: 16, B: 15), and the remaining patients were classified as borderline resectable (A: 5, B: 4). Of the 12 evaluable patients, 3 achieved partial response under neoadjuvant FOLFIRINOX. Of the 21 patients in arm A and 19 patients in arm B, 17 and 7 underwent curative surgery, and R0-resection was achieved in 77% and 71%, respectively. Perioperative morbidity occurred in 72% in arm A and 46% in arm B, whereas non-surgical toxicity was comparable in both arms. Median RFS/PFS was almost doubled in arm B (14.1 months) compared with arm A (8.4 months) in the population with surgical resection, whereas median OS was comparable between both arms.

Conclusions: Although the analysis was only descriptive owing to small patient numbers, no safety issues regarding surgical complications were observed in the perioperative FOLFIRINOX arm. Thus, considering the small number of patients, perioperative treatment approach appears feasible and potentially effective in well-selected cohorts of patients. In pancreatic cancer, patient selection before initiation of neoadjuvant therapy appears to be critical.

Keywords: Adjuvant; FOLFIRINOX; Neoadjuvant; Resectable pancreatic cancer.

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Conflict of interest statement

Thorsten O. Goetze consults for Amgen, AstraZeneca, Bayer, BMS, Daiichi Sankyo, Foundation One Medicine, Lilly, MCI, MSD, Novartis, Roche, and Boehringer and received honoraria from Amgen, BMS, Lilly, MSD, Novartis, Roche, and GSK. Wolf O. Bechstein received honoraria from Astellas, Charité Berlin, CHIESI, Deutscher Ärzteverlag, Else-Kröner-Stiftung, European Society for Organ Transplantation, Falk Foundation, GORE, MCI, Novartis, Sanofi, Sirtex, and Terumo. Gabriele M. Siegler consults for AstraZeneca, BMS, Janssen-Cilag, Novartis; receives honoraria from Aurikamed, BMS, Deutsche Röntgengesellschaft, Eisai, Janssen-Cilag, Konzept Pharma, Roche; research grants from Novartis and Nutricia; and travel grants from Amgen, Novarti, and Servier. Salah-Eddin Al-Batran is the CEO/funder of Institut für Klinische Krebsforschung IKF; is on the advisory board of BMS, Immutep, Lilly, MacroGenics, and MSD; received research grants from Astra-Zeneca, BMS, Celgene, Eurozyto, Hospira, Immutep, Ipsen, Lilly, Medac, MSD, Roche, Sanofi, and Vifor; and is a speaker for AIO Studien gGmbH, BMS, Lilly, and MCI. Marino Venerito received honoraria for speaker, consultancy, advisory role, and/or research grants from Servier, Roche, BMS, MSD, EISAI, Bayer, Lilly, AstraZeneca, Merck Serono, Sirtex, Ipsen, Nordic Pharma, and Amgen. Ulli Bankstahl, Claudia Pauligk, Maria Loose, and Nils Homann have no conflicts of interest to declare. Possible conflicts of other authors tbn.

Figures

Fig. 1
Fig. 1
CONSORT diagram; all 40 patients who were randomly assigned were included in the intention-to-treat population, and the curative resected population comprised all patients who received radical oncological pancreatic surgery (N = 17 arm A, N = 7 arm B)
Fig. 2
Fig. 2
Overall and recurrence/progression-free survival; overall survival and recurrence/progression-free survival in the intention-to-treat (ITT) (A) and the curative resected population (B) in the adjuvant gemcitabine (Gem) arm A versus the FOLFIRINOX (FFX) arm B
See this image and copyright information in PMC

References

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