Systemic treatment of advanced pancreatic cancer: A Comprehensive Review
References
- Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–263.
https://doi.org/10.3322/caac.21834 - Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer; 2024. Available from:
https://gco.iarc.who.int/today - O'Kane GM, Lowery MA. Moving the needle on precision medicine in pancreatic cancer. J Clin Oncol. 2022;40(24):2693–2705.
https://doi.org/10.1200/jco.21.02514 - Poruk KE, Firpo MA, Adler DG, Mulvihill SJ. Screening for pancreatic cancer. Ann Surg. 2012;257(1):17–26.
https://doi.org/10.1097/sla.0b013e31825ffbfb - Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet. 2011;378(9791):607–620.
https://doi.org/10.1016/s0140-6736(10)62307-0 - Weinerman BH, MacCormick RE. A phase II survival comparison of patients with adenocarcinoma of the pancreas treated with 5-fluorouracil and calcium leucovorin versus a matched tumor registry control population. Am J Clin Oncol. 1994;17(6):467–469.
https://doi.org/10.1097/00000421-199412000-00002 - Carmichael J, Fink U, Russell R, Spittle M, Harris A, Spiessi G, Blatter J. Phase II study of gemcitabine in patients with advanced pancreatic cancer. Br J Cancer. 1996;73(1):101–105.
https://doi.org/10.1038/bjc.1996.18 - Rothenberg M, Moore M, Cripps M, Andersen J, Portenoy R, Burriss H, Green T, Tarassoff P, Brown T, Casper E, Storniolo A, Von Hoff D. A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol. 1996;7(4):347–353.
https://doi.org/10.1093/oxfordjournals.annonc.a010600 - Burris H, Storniolo A. Assessing clinical benefit in the treatment of pancreas cancer: gemcitabine compared to 5-fluorouracil. Eur J Cancer. 1997;33 Suppl:S18–S22.
https://doi.org/10.1016/s0959-8049(96)00324-3 - Katayama ES, Hue JJ, Bajor DL, Ocuin LM, Ammori JB, Hardacre JM, Winter JM. A comprehensive analysis of clinical trials in pancreatic cancer: what is coming down the pike? Oncotarget. 2020;11(38):3489–3501.
https://doi.org/10.18632/oncotarget.27727 - Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, Harper PG, Dunn J, Tudur-Smith C, West J, Falk S, Crellin A, Adab F, Thompson J, Leonard P, Ostrowski J, Eatock M, Scheithauer W, Herrmann R, Neoptolemos JP. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009;27(33):5513–18.
https://doi.org/10.1200/jco.2009.24.2446 - Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25(15):1960–66.
https://doi.org/10.1200/jco.2006.07.9525 - Stein SM, James ES, Deng Y, Cong X, Kortmansky JS, Li J, Staugaard C, Indukala D, Boustani AM, Patel V, Cha CH, Salem RR, Chang B, Hochster HS, Lacy J. Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. Br J Cancer. 2016;114(7):737–43.
https://doi.org/10.1038/bjc.2016.45 - Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul J, Gourgou-Bourgade S, De La Fouchardière C, Bennouna J, Bachet J, Khemissa-Akouz F, Péré-Vergé D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M. FOLFIRINOX versus gemcitabine for meta-static pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.
https://doi.org/10.1056/nejmoa1011923 - Tong H, Fan Z, Liu B, Lu T. The benefits of modified FOLFIRINOX for advanced pancreatic cancer and its induced adverse events: a systematic review and meta-analysis. Sci Rep. 2018;8(1):1–10.
https://doi.org/10.1038/s41598-018-26811-9 - Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Wee W, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703.
https://doi.org/10.1056/nejmoa1304369 - Taieb J, Prager GW, Melisi D, Westphalen CB, D'Esquermes N, Ferreras A, Carrato A, Macarulla T. First-line and second-line treatment of patients with metastatic pancreatic adenocarcinoma in routine clinical practice across Europe: a retrospective, observational chart review study. ESMO Open. 2020;5(1):e000587.
https://doi.org/10.1136/esmoopen-2019-000587 - Wang-Gillam A, Hubner RA, Siveke JT, Von Hoff DD, Belanger B, De Jong FA, Mirakhur B, Chen L. NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: final overall survival analysis and characteristics of long-term survivors. Eur J Cancer. 2019;108:78–87.
https://doi.org/10.1016/j.ejca.2018.12.007 - De Almeida MJ, De Mello CAL, Camandaroba MPG, De Jesus VHF. Fluoropyrimidine-based maintenance chemotherapy after FOLFIRINOX for patients with metastatic pancreatic adenocarcinoma: a retrospective analysis. Ann Pancreat Cancer. 2020;3:13.
https://doi.org/10.21037/apc-20-27 - Shao F, Duan Y, Zhao Y, Li Y, Liu J, Zhang C, He S. PARP inhibitors in breast and ovarian cancer with BRCA mutations: a meta-analysis of survival. Aging (Albany NY). 2021;13(6):8975–88.
https://doi.org/10.18632/aging.202724 - Rosen MN, Goodwin RA, Vickers MM. BRCA mutated pancreatic cancer: a change is coming. World J Gastroenterol. 2021;27(17):1943–58.
https://doi.org/10.3748/wjg.v27.i17.1943 - Kindler HL, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh D, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, Bordia S, McGuinness D, Cui K, Locker GY, Golan T. Overall survival results from the POLO Trial: a phase III study of active maintenance olaparib versus placebo for germline BRCA-mutated metastatic pancreatic cancer. J Clin Oncol. 2022;40(34):3929–39.
https://doi.org/10.1200/jco.21.01604 - Shroff RT, Hendifar A, McWilliams RR, Geva R, Epelbaum R, Rolfe L, Goble S, Lin KK, Biankin AV, Giordano H, Vonderheide RH, Domchek SM. Rucaparib monotherapy in patients with pancreatic cancer and a known deleterious BRCA mutation. JCO Precis Oncol. 2018;2:1–15.
https://doi.org/10.1200/po.17.00316 - Carrato A, Pazo-Cid R, Macarulla T, Gallego J, Jiménez-Fonseca P, Rivera F, Cano MT, Rodriguez-Garrote M, Pericay C, Alés I, Layos L, Graña B, Iranzo V, Gallego I, Garcia-Carbonero R, De Mena IR, Guillén-Ponce C, Aranda E. Nab-paclitaxel plus gemcitabine and FOLFOX in metastatic pancreatic cancer. NEJM Evid. 2024;3(2).
https://doi.org/10.1056/evidoa2300144 - Hidalgo M, Cascinu S, Kleeff J, Labianca R, Löhr J, Neoptolemos J, Real FX, Van Laethem J, Heinemann V. Addressing the challenges of pancreatic cancer: future directions for improving outcomes. Pancreatology. 2014;15(1):8–18.
https://doi.org/10.1016/j.pan.2014.10.001 - Ferrer M, Anthony TG, Ayres JS, Biffi G, Brown JC, Caan BJ, Feliciano EMC, Coll AP, Dunne RF, Goncalves MD, Grethlein J, Heymsfield SB, Hui S, Jamal-Hanjani M, Lam JM, Lewis DY, McCandlish D, Mustian KM, O'Rahilly S, Janowitz T. Cachexia: a systemic consequence of progressive, unresolved disease. Cell. 2023;186(9):1824–45.
https://doi.org/10.1016/j.cell.2023.03.028 - Solheim TS, Laird BJA, Balstad TR, Stene GB, Baracos V, Bye A, Dajani O, Hendifar AE, Strasser F, Chasen MR, Maddocks M, Simpson MR, Skovlund E, Griffiths GO, Hicks J, Graham JS, Kyle F, Bowden J, Fallon MT, Kaasa S. Results from a randomized, open-label trial of a multimodal intervention (exercise, nutrition, and anti-inflammatory medication) plus standard care versus standard care alone to attenuate cachexia in patients with advanced cancer undergoing chemotherapy. J Clin Oncol. 2024;42(17 Suppl):LBA12007.
https://doi.org/10.1200/jco.2024.42.17_suppl.lba12007 - Martinelli P, Pau ECS, Cox T, Sainz B Jr, Dusetti N, Greenhalf W, Rinaldi L, Costello E, Ghaneh P, Malats N, Büchler M, Pajic M, Biankin A, Iovanna JL, Neoptolemos J, Real FX. GATA6 regulates EMT and tumor dissemination and is a marker of response to adjuvant chemotherapy in pancreatic cancer. Gut. 2016;66(9):1665–76.
https://doi.org/10.1136/gutjnl-2015-311256 - O'Kane GM, Fischer S, Denroche R, Jang GH, Zhang A, Dodd A, Grant RC, Grunwald B, Masoomian MM, Moura S, Elimova E, Prince RM, Zogopoulos G, Notta F, Wilson J, Gallinger S, Knox JJ. Integrative molecular profiling and response to chemotherapy on the COMPASS trial. J Clin Oncol. 2019;37(4 Suppl):188.
https://doi.org/10.1200/jco.2019.37.4_suppl.188 - Graham JS, Valle JW, Evans TJ, Grose DB, Paul J, Stobo J, Cooke S, Dixon-Hughes J, Weir H, Mohan S, Biankin A, Chang DK. PRIMUS-001: An adaptive phase II study of FOLFOX-A (FOLFOX and nab-paclitaxel) versus AG (nab-paclitaxel and gemcitabine) in patients with metastatic pancreatic cancer, with integrated bio-marker evaluation (ISRCTN75002153) – Part of Precision-Panc. J Clin Oncol. 2018;36(15 Suppl):TPS4158.
https://doi.org/10.1200/jco.2018.36.15_suppl.tps4158 - Shindo K, Yu J, Suenaga M, Fesharakizadeh S, Cho C, Macgregor-Das A, Siddiqui A, Witmer PD, Tamura K, Song TJ, Almario JAN, Brant A, Borges M, Ford M, Barkley T, He J, Weiss MJ, Wolfgang CL, Roberts NJ, Goggins M. Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma. J Clin Oncol. 2017;35(30):3382–90.
https://doi.org/10.1200/jco.2017.72.3502 - Middha S, Zhang L, Nafa K, Jayakumaran G, Wong D, Kim HR, Sadowska J, Berger MF, Delair DF, Shia J, Stadler Z, Klimstra DS, Ladanyi M, Zehir A, Hechtman JF. Reliable pan-cancer microsatellite instability assessment by using targeted next-generation sequencing data. JCO Precis Oncol. 2017;1:1–17.
https://doi.org/10.1200/po.17.00084 - NCCN. Pancreatic adenocarcinoma guidelines. Available from:
https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455 [Accessed June 2025] - Okamura R, Boichard A, Kato S, Sicklick JK, Bazhenova L, Kurzrock R. Analysis of NTRK alterations in pan-cancer adult and pediatric malignancies: implications for NTRK-targeted therapeutics. JCO Precis Oncol. 2018;2:1–20.
https://doi.org/10.1200/po.18.00183 - Hong DS, DuBois SG, Kummar S, Farago AF, Albert CM, Rohrberg KS, Van Tilburg CM, Nagasubramanian R, Berlin JD, Federman N, Mascarenhas L, Geoerger B, Dowlati A, Pappo AS, Bielack S, Doz F, McDermott R, Patel JD, Schilder RJ, Drilon A. Larotrectinib in patients with TRK fusion-positive solid tumors: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol. 2020;21(4):531–40.
https://doi.org/10.1016/s1470-2045(19)30856-3
DOI: https://doi.org/10.2478/jcas-2026-0020 | Journal eISSN: 2411-989X
Language: English
Page range: 145 - 152
Published on: Sep 10, 2026
Published by: Shakuat Khanum Memorial Cancer Hospital and Research Centre
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© 2026 Jamshed Ali, Maria Qubtia, Amer Rehman Farrooqi, Irfan Ul Islam Nasir, Muhammad Fahd Shah, Syed Irfan Kabir, published by Shakuat Khanum Memorial Cancer Hospital and Research Centre
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