- •Survival outcomes for patients with pancreatic cancer remain poor.
- •FOLFIRINOX and gemcitabine plus nab-paclitaxel are the treatments of choice for patients who are not surgical candidates; both combinations have shown a survival advantage over previously standard gemcitabine monotherapy.
- •Second-line therapies, especially nanoliposomal irinotecan plus 5 fluorouracil–folinic acid, might prolong survival after first-line gemcitabine failure.
- •Beyond the standard of care, there is a lack of molecular and genetic biomarkers for optimal stratification of patients and in guiding treatment decisions.
- •Focusing clinical trial designs on molecular screening of patients will be crucial, and drug combination strategy seems the most interesting approach.
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- Current clinical strategies of pancreatic cancer treatment and open molecular questions.Int J Mol Sci. 2019; 20: 4543https://doi.org/10.3390/ijms20184543
- Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin. 2018; 68: 394-424https://doi.org/10.3322/caac.21492
- More deaths from pancreatic cancer than breast cancer in the EU by 2017.Acta Oncol. 2016; 55: 1158-1160https://doi.org/10.1080/0284186X.2016.1197419
- Epidemiology of pancreatic cancer: global trends, etiology and risk factors.World J Oncol. 2019; 10: 10-27
- Global surveillance of trends in cancer survival 2000–14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries.The Lancet. 2018; 391: 1023-1075https://doi.org/10.1016/S0140-6736(17)33326-3
- Cancer statistics, 2019.CA Cancer J Clin. 2019; 69: 7-34https://doi.org/10.3322/caac.21551
American Cancer Society. Cancer Facts & Figures 1999–2020, https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2020.html; 2020 (accessed 5 March 2021).
- Trends in pancreatic cancer survival in Switzerland.Schweiz Krebsbulletin Nr. 2013; 42013: 328-332
- Cancer statistics, 2020.CA Cancer J Clin. 2020; 70: 7-30https://doi.org/10.3322/caac.21590
BFS. Swiss National Cancer Statistics - Fact sheet, https://www.bfs.admin.ch/bfs/en/home/statistics/health/surveys/ke.assetdetail.6706410.html; 2018 (accessed 5 March 2021).
BFS. Cancer, https://www.bfs.admin.ch/bfs/en/home/statistics/health/state-health/diseases/cancer.html; 2020 (accessed 5 March 2021).
Swiss cancer report 2015 - Current situation and developments. https://www.bfs.admin.ch/bfs/en/home/statistics/health.assetdetail.428987.html; 2016 (accessed 5 March 2021).
National statistics on cancer incidence NICER. https://www.nicer.org/en/statistics-atlas/cancer-incidence (accessed 5 March 2021).
- Epidemiology and risk factors of pancreatic cancer.Acta Bio Medica Atenei Parm. 2018; 89: 141-146
- AJCC cancer staging manual.8th ed. Springer, New York (NY)2017
- Pancreatic cancer: a review of clinical diagnosis, epidemiology, treatment and outcomes.World J Gastroenterol. 2018; 24: 4846-4861https://doi.org/10.3748/wjg.v24.i43.4846
- The impact of metastatic sites in advanced pancreatic adenocarcinoma, systematic review and meta-analysis of prospective randomized studies.PLoS ONE. 2020; 15https://doi.org/10.1371/journal.pone.0230060
- Computational modeling of pancreatic cancer reveals kinetics of metastasis suggesting optimum treatment strategies.Cell. 2012; 148: 362-375https://doi.org/10.1016/j.cell.2011.11.060
- Precision oncology for hepato-pancreato-biliary (HPB) cancers: state of the art and future directions.Heal TIMES Oncol Hematol. 2020; : 52-59
- Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†.Ann Oncol. 2019; 30: 1558-1571https://doi.org/10.1093/annonc/mdz233
- FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer.N Engl J Med. 2011; 364: 1817-1825https://doi.org/10.1056/NEJMoa1011923
- Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial.Lancet Lond Engl. 2017; 389: 1011-1024https://doi.org/10.1016/S0140-6736(16)32409-6
- Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial.JAMA. 2013; 310: 1473-1481https://doi.org/10.1001/jama.2013.279201
ESMO Guidelines Committee. eUpdate – Cancer of the Pancreas Treatment Recommendations, https://www.esmo.org/guidelines/gastrointestinal-cancers/pancreatic-cancer/eupdate-cancer-of-the-pancreas-treatment-recommendations; 2019 [accessed 5 March 2021]. n.d.
- ESPAC-5F: Four-arm, prospective, multicenter, international randomized phase II trial of immediate surgery compared with neoadjuvant gemcitabine plus capecitabine (GEMCAP) or FOLFIRINOX or chemoradiotherapy (CRT) in patients with borderline resectable pancreatic cancer.J Clin Oncol. 2020; 38: 4505https://doi.org/10.1200/JCO.2020.38.15_suppl.4505
- Alliance A021501: Preoperative mFOLFIRINOX or mFOLFIRINOX plus hypofractionated radiation therapy (RT) for borderline resectable (BR) adenocarcinoma of the pancreas.J Clin Oncol. 2021; 39: 377https://doi.org/10.1200/JCO.2021.39.3_suppl.377
- Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial.J Clin Oncol. 1997; 15: 2403-2413https://doi.org/10.1200/JCO.1918.104.22.1683
Gemcitabin Labatec®. Product information. Swissmedic, https://www.swissmedicinfo.ch; 2019 (accessed May 20, 2020).
- Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine.N Engl J Med. 2013; 369: 1691-1703https://doi.org/10.1056/NEJMoa1304369
- nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: a subgroup analysis of the Western European cohort of the MPACT trial.OncoTargets Ther. 2017; 10: 591-596https://doi.org/10.2147/OTT.S124097
- Dose modification and efficacy of nab-paclitaxel plus gemcitabine vs. gemcitabine for patients with metastatic pancreatic cancer: phase III MPACT trial.J Gastrointest Oncol. 2016; 7: 469-478
- nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III Trial. JNCI.J Natl Cancer Inst. 2015; 107 (dju413–dju413)https://doi.org/10.1093/jnci/dju413
- Real-world outcomes of FOLFIRINOX vs gemcitabine and nab-paclitaxel in advanced pancreatic cancer: a population-based propensity score-weighted analysis.Cancer Med. 2019; 9: 160-169https://doi.org/10.1002/cam4.2705
- Choice of first line systemic treatment in pancreatic cancer among national experts.Pancreatol Off J Int Assoc Pancreatol IAP Al. 2020; S1424–3903https://doi.org/10.1016/j.pan.2020.03.012
- Liposomal Irinotecan + 5-FU/LV in metastatic pancreatic cancer.Pancreas. 2020; 49: 62-75https://doi.org/10.1097/MPA.0000000000001455
- An update on treatment options for pancreatic adenocarcinoma.Ther Adv Med Oncol. 2019; 11https://doi.org/10.1177/1758835919875568
- 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; 5https://doi.org/10.1136/esmoopen-2019-000587
- Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after Folfirinox failure: an AGEO prospective multicentre cohort.Br J Cancer. 2015; 113: 989-995https://doi.org/10.1038/bjc.2015.328
- Systematic review and meta-analysis of gemcitabine-based chemotherapy after FOLFIRINOX in advanced pancreatic cancer.Ther Adv Med Oncol. 2020; 12https://doi.org/10.1177/1758835920905408
- Retrospective analysis of efficacy and safety of Gemcitabine-based chemotherapy in patients with metastatic pancreatic adenocarcinoma experiencing disease progression on FOLFIRINOX.J Gastrointest Oncol. 2018; 9: 806-819
- Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the CONKO-003 trial.J Clin Oncol Off J Am Soc Clin Oncol. 2014; 32: 2423-2429https://doi.org/10.1200/JCO.2013.53.6995
- PANCREOX: a randomized phase III study of fluorouracil/leucovorin with or without oxaliplatin for second-line advanced pancreatic cancer in patients who have received gemcitabine-based chemotherapy.J Clin Oncol. 2016; 34: 3914-3920https://doi.org/10.1200/JCO.2016.68.5776
Onivyde®. Product information. Swissmedic, https://www.swissmedicinfo.ch; 2019 (accessed 5 March 2021).
- Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial.The Lancet. 2016; 387: 545-557https://doi.org/10.1016/S0140-6736(15)00986-1
- Quality of life in metastatic pancreatic cancer patients receiving liposomal irinotecan plus 5-fluorouracil and leucovorin.Eur J Cancer. 2019; 106: 24-33https://doi.org/10.1016/j.ejca.2018.09.029
- 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: 78-87https://doi.org/10.1016/j.ejca.2018.12.007
- Liposomal irinotecan and 5-fluorouracil/leucovorin in older patients with metastatic pancreatic cancer – A subgroup analysis of the pivotal NAPOLI-1 trial.J Geriatr Oncol. 2019; 10: 427-435https://doi.org/10.1016/j.jgo.2019.02.011
- Sequential treatment of metastatic adenocarcinoma of the pancreatic duct with liver metastasis following the NAPOLI-1 study protocol with nal-irinotecan plus 5-FU in the second line.Case Reps Oncol. 2020; 13: 79-84https://doi.org/10.1159/000504471
- A real-world analysis of second-line treatment options in pancreatic cancer: liposomal-irinotecan plus 5-fluorouracil and folinic acid.Ther Adv Med Oncol. 2019; 11https://doi.org/10.1177/1758835919853196
- Multicenter retrospective analysis of second-line therapy after gemcitabine plus nab-paclitaxel in advanced pancreatic cancer patients.Cancers. 2020; 12: 1311https://doi.org/10.3390/cancers12051131
- Real-world dosing patterns and outcomes of patients with metastatic pancreatic cancer treated with a liposomal irinotecan regimen in the United States.Pancreas. 2020; 49: 193-200https://doi.org/10.1097/MPA.0000000000001479
- Results from the prospective German TPK clinical cohort study: Treatment algorithms and survival of 1,174 patients with locally advanced, inoperable, or metastatic pancreatic ductal adenocarcinoma.Int J Cancer. 2019; 144: 981-990https://doi.org/10.1002/ijc.31751
- Plasma IL8 is a biomarker for TAK1 activation and predicts resistance to nanoliposomal irinotecan in patients with gemcitabine-refractory pancreatic cancer.Clin Cancer Res Off J Am Assoc Cancer Res. 2020; 26: 4661-4669https://doi.org/10.1158/1078-0432.CCR-20-0395
- TAK-ing aim at chemoresistance: the emerging role of MAP3K7 as a target for cancer therapy.Drug Resist Updat Rev Comment Antimicrob Anticancer Chemother. 2017; 33–35: 36-42https://doi.org/10.1016/j.drup.2017.10.004
- Nomogram for predicting survival in patients treated with liposomal irinotecan plus fluorouracil and leucovorin in metastatic pancreatic cancer.Cancers. 2019; 11: 1068https://doi.org/10.3390/cancers11081068
- Mismatch-repair deficiency predicts response of solid tumors to PD-1 blockade.Science. 2017; 357: 409-413https://doi.org/10.1126/science.aan6733
- Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: results from the phase II KEYNOTE-158 study.J Clin Oncol. 2019; 38: 1-10https://doi.org/10.1200/JCO.19.02105
A Phase 2 Study of Cabiralizumab (BMS-986227, FPA008) Administered in Combination With Nivolumab (BMS-936558) With and Without Chemotherapy in Patients With Advanced Pancreatic Cancer (NCT03336216). clinicaltrials.gov; 2020.
Five Prime Therapeutics Provides Update on Phase 2 Trial of Cabiralizumab Combined with Opdivo® in Pancreatic Cancer, http://investor.fiveprime.com/news-releases/news-release-details/five-prime-therapeutics-provides-update-phase-2-trial, 2020(accessed 5 March 2021).
Cabiralizumab Misses Primary End Point in Phase II Trial of Advanced Pancreatic Cancer, https://www.targetedonc.com/view/cabiralizumab-misses-primary-end-point-in-phase-ii-trial-of-advanced-pancreatic-cancer; 2021 (accessed 5 March 2021).
- Randomized phase III study of FOLFOX alone and with pegilodecakin as second-line therapy in patients with metastatic pancreatic cancer (SEQUOIA).J Clin Oncol. 2020; 38: 637https://doi.org/10.1200/JCO.2020.38.4_suppl.637
Renouf DJ, Knox JJ, Kavan P, Jonker D, Welch S, Couture F, et al. LBA65 The Canadian Cancer Trials Group PA.7 trial: Results of a randomized phase II study of gemcitabine (GEM) and nab-paclitaxel (Nab-P) vs GEM, nab-P, durvalumab (D) and tremelimumab (T) as first line therapy in metastatic pancreatic ductal adenocarcinoma (mPDAC). Ann Oncol 2020;31:S1195. https://doi.org/10.1016/j.annonc.2020.08.2300.
- Immune therapies in pancreatic ductal adenocarcinoma: where are we now?.World J Gastroenterol. 2018; 24: 2137-2151https://doi.org/10.3748/wjg.v24.i20.2137
- Maintenance olaparib for germline BRCA -mutated metastatic pancreatic cancer.N Engl J Med. 2019; (NEJMoa1903387)https://doi.org/10.1056/NEJMoa1903387
Lynparza®. European Medicines Agency. https://www.ema.europa.eu/en/medicines/human/EPAR/lynparza; 2020 (accessed 5 March 2021).
Lynparza®. Product information. Swissmedic, http://www.swissmedicinfo.ch; 2020 (accessed 5 March 2021).
- Randomized, multicenter, phase II trial of gemcitabine and cisplatin with or without veliparib in patients with pancreas adenocarcinoma and a germline BRCA/PALB2 mutation.J Clin Oncol. 2020; 38: 1378-1388https://doi.org/10.1200/JCO.19.02931
- Family history as a marker of platinum sensitivity in pancreatic adenocarcinoma.Cancer Chemother Pharmacol. 2015; 76: 489-498https://doi.org/10.1007/s00280-015-2788-6
- 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: 1960-1966https://doi.org/10.1200/JCO.2006.07.9525
- Cetuximab in pancreatic cancer therapy: a systematic review and meta-analysis.Oncology. 2020; 98: 53-60https://doi.org/10.1159/000502844
- Randomized phase III trial of pegvorhyaluronidase alfa with nab-paclitaxel plus gemcitabine for patients with hyaluronan-high metastatic pancreatic adenocarcinoma.J Clin Oncol. 2020; (JCO.20.00590)https://doi.org/10.1200/JCO.20.00590
- Palbociclib in patients with pancreatic and biliary cancer with CDKN2A alterations: results from the targeted agent and profiling utilization registry study.JCO Precis Oncol. 2019; : 1-8https://doi.org/10.1200/PO.19.00124
- CDK4/6 inhibitors impair recovery from cytotoxic chemotherapy in pancreatic adenocarcinoma.Cancer Cell. 2020; 37e6https://doi.org/10.1016/j.ccell.2020.01.007
- Molecular subtypes of pancreatic cancer.Nat Rev Gastroenterol Hepatol. 2019; 16: 207-220https://doi.org/10.1038/s41575-019-0109-y
- Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: a retrospective analysis of the Know Your Tumor registry trial.Lancet Oncol. 2020; 21: 508-518https://doi.org/10.1016/S1470-2045(20)30074-7
- Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group.Ann Oncol Off J Eur Soc Med Oncol. 2020; 31: 1491-1505https://doi.org/10.1016/j.annonc.2020.07.014
- Organoid profiling identifies common responders to chemotherapy in pancreatic cancer.Cancer Discov. 2018; 8: 1112-1129https://doi.org/10.1158/2159-8290.CD-18-0349
- Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution.Nat Genet. 2020; 52: 231-240https://doi.org/10.1038/s41588-019-0566-9
- Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children.N Engl J Med. 2018; 378: 731-739https://doi.org/10.1056/NEJMoa1714448
- Targeting the untargetable KRAS in cancer therapy.Acta Pharm Sin B. 2019; 9: 871-879https://doi.org/10.1016/j.apsb.2019.03.002
- Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 510, a novel small molecule KRAS G12C inhibitor, in advanced solid tumors.J Clin Oncol. 2019; 37: 3003https://doi.org/10.1200/JCO.2019.37.15_suppl.3003
- KRAS mutant pancreatic cancer: no lone path to an effective treatment.Cancers. 2016; 8https://doi.org/10.3390/cancers8040045
- KRASG12C inhibition with sotorasib in advanced solid tumors.N Engl J Med. 2020; 383: 1207-1217https://doi.org/10.1056/NEJMoa1917239
- KRYSTAL-1: activity and safety of adagrasib (MRTX849) in patients with colorectal cancer (CRC) and other solid tumors harboring a KRAS G12C mutation.Eur J Cancer. 2020; 138: S2https://doi.org/10.1016/S0959-8049(20)31077-7
- NRG1 gene fusions are recurrent, clinically actionable gene rearrangements in KRAS wild-type pancreatic ductal adenocarcinoma.Clin Cancer Res Off J Am Assoc Cancer Res. 2019; 25: 4674-4681https://doi.org/10.1158/1078-0432.CCR-19-0191
- First-in-human phase 1/2 study of MCLA-128, a full length IgG1 bispecific antibody targeting HER2 and HER3: final phase 1 data and preliminary activity in HER2+ metastatic breast cancer (MBC).J Clin Oncol. 2017; 35: 2522https://doi.org/10.1200/JCO.2017.35.15_suppl.2522
- Phase I/II study of single agent MCLA-128, a full length IgG1 bispecific antibody targeting the HER3 pathway: overall safety at the recommended phase II dose (R2PD) and preliminary activity in HER2+ metastatic gastric/gastroesophageal junction cancer (GC/GEJ).Ann Oncol. 2018; 29: viii223-viii224https://doi.org/10.1093/annonc/mdy282.048
- Cytosolic 5′-nucleotidase 1A is overexpressed in pancreatic cancer and mediates gemcitabine resistance by reducing intracellular gemcitabine metabolites.EBioMedicine. 2019; 40: 394-405https://doi.org/10.1016/j.ebiom.2019.01.037
- Drug resistance in pancreatic cancer: New player caught in act.EBioMedicine. 2019; 40: 39-40https://doi.org/10.1016/j.ebiom.2019.02.008
- Targeted therapies in the management of locally advanced and metastatic pancreatic cancer: a systematic review.Oncotarget. 2018; 9: 21613-21627