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Multicenter Study
. 2020 Nov 1;6(11):1733-1740.
doi: 10.1001/jamaoncol.2020.3537.

Evaluation of Adjuvant Chemotherapy in Patients With Resected Pancreatic Cancer After Neoadjuvant FOLFIRINOX Treatment

Stijn van Roessel  1 , Eran van Veldhuisen  1 , Sjors Klompmaker  1   2 , Quisette P Janssen  3 , Mohammed Abu Hilal  4   5 , Adnan Alseidi  6   7 , Alberto Balduzzi  8 , Gianpaolo Balzano  9 , Claudio Bassi  8 , Frederik Berrevoet  10 , Morgan Bonds  6 , Olivier R Busch  1 , Giovanni Butturini  11 , Marco Del Chiaro  12 , Kevin C Conlon  13 , Massimo Falconi  9 , Isabella Frigerio  11 , Giuseppe K Fusai  14 , Johan Gagnière  15   16 , Oonagh Griffin  15 , Thilo Hackert  17 , Asif Halimi  18 , Ulla Klaiber  17 , Knut J Labori  19 , Giuseppe Malleo  8 , Marco V Marino  20   21 , Michael B Mortensen  22 , Andrej Nikov  23 , Mickaël Lesurtel  24 , Tobias Keck  25 , Jörg Kleeff  26 , Rupaly Pandé  27 , Per Pfeiffer  28 , D Pietrasz  29 , Keith J Roberts  27 , Antonio Sa Cunha  29 , Roberto Salvia  8 , Oliver Strobel  17 , Timo Tarvainen  30 , Patrick M Bossuyt  31 , Hanneke W M van Laarhoven  32 , Johanna W Wilmink  32 , Bas Groot Koerkamp  3 , Marc G Besselink  1 ; European-African Hepato-Pancreato-Biliary Association
Affiliations
Multicenter Study

Evaluation of Adjuvant Chemotherapy in Patients With Resected Pancreatic Cancer After Neoadjuvant FOLFIRINOX Treatment

Stijn van Roessel et al. JAMA Oncol. .

Abstract

Importance: The benefit of adjuvant chemotherapy after resection of pancreatic cancer following neoadjuvant combination treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) is unclear.

Objective: To assess the association of adjuvant chemotherapy with overall survival (OS) in patients after pancreatic cancer resection and neoadjuvant FOLFIRINOX treatment.

Design, setting, and participants: This international, multicenter, retrospective cohort study was conducted from January 1, 2012, to December 31, 2018. An existing cohort of patients undergoing resection of pancreatic cancer after FOLFIRINOX was updated and expanded for the purpose of this study. All consecutive patients who underwent pancreatic surgery after at least 2 cycles of neoadjuvant FOLFIRINOX chemotherapy for nonmetastatic pancreatic cancer were retrospectively identified from institutional databases. Patients with resectable pancreatic cancer, borderline resectable pancreatic cancer, and locally advanced pancreatic cancer were eligible for this study. Patients with in-hospital mortality or who died within 3 months after surgery were excluded.

Exposures: The association of adjuvant chemotherapy with OS was evaluated in different subgroups including interaction terms for clinicopathological parameters with adjuvant treatment in a multivariable Cox model. Overall survival was defined as the time starting from surgery plus 3 months (moment eligible for adjuvant therapy), unless mentioned otherwise.

Results: We included 520 patients (median [interquartile range] age, 61 [53-66] years; 279 [53.7%] men) from 31 centers in 19 countries. The median number of neoadjuvant cycles of FOLFIRINOX was 6 (interquartile range, 5-8). Overall, 343 patients (66.0%) received adjuvant chemotherapy, of whom 68 (19.8%) received FOLFIRINOX, 201 (58.6%) received gemcitabine-based chemotherapy, 14 (4.1%) received capecitabine, 45 (13.1%) received a combination or other agents, and 15 (4.4%) received an unknown type of adjuvant chemotherapy. Median OS was 38 months (95% CI, 36-46 months) after diagnosis and 31 months (95% CI, 29-37 months) after surgery. No survival difference was found for patients who received adjuvant chemotherapy vs those who did not (median OS, 29 vs 29 months, univariable hazard ratio [HR], 0.99; 95% CI, 0.77-1.28; P = .93). In multivariable analysis, only the interaction term for lymph node stage with adjuvant therapy was statistically significant: In patients with pathology-proven node-positive disease, adjuvant chemotherapy was associated with improved survival (median OS, 26 vs 13 months; multivariable HR, 0.41 [95% CI, 0.22-0.75]; P = .004). In patients with node-negative disease, adjuvant chemotherapy was not associated with improved survival (median OS, 38 vs 54 months; multivariable HR, 0.85; 95% CI, 0.35-2.10; P = .73).

Conclusions and relevance: These results suggest that adjuvant chemotherapy after neoadjuvant FOLFIRINOX and resection of pancreatic cancer was associated with improved survival only in patients with pathology-proven node-positive disease. Future randomized studies should be conducted to confirm this finding.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Balzano reported receiving personal fees from Celgene and Roche Diabetics outside the submitted work. Dr Butturini reported receiving personal fees from Roche Diabetics outside the submitted work. Dr del Chiaro reported receiving an industry grant from Haemonetics Inc to conduct a multicenter study outside the submitted work. Dr Griffin reported receiving grants from Health Research Board Ireland outside the submitted work. Dr Sa Cunha reported receiving personal fees from Merck, Sanofi, Baxter, Biom’Up USA, and Servier Laboratories outside the submitted work. Dr van Laarhoven reported receiving grants and personal fees from Bristol Myers Squibb, Lilly, and Servier Laboratories; personal fees from Merck Sharp & Dohme and Novartis; grants, personal fees, and nonfinancial support from Nordic Pharma; grants and nonfinancial support from Bayer, Celgene, and Roche; and grants from Janssen and Philips outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Overall Survival Outcomes Stratified by Receipt of Adjuvant Therapy
CTx indicates chemotherapy.
See this image and copyright information in PMC

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