Evidence Review
Copyright ©The Author(s) 2021.
World J Gastroenterol. May 7, 2021; 27(17): 1847-1863
Published online May 7, 2021. doi: 10.3748/wjg.v27.i17.1847
Table 1 Studies of second-line treatment in metastatic pancreatic ductal adenocarcinoma
Type of study
Patients (n)
1st-line regimen
2nd-line regimen
Median 2nd-line OS (mo)
Median 2nd-line PFS (mo)
2nd-line ORR (%)
2nd-line DCR (%)
Pelzer et al[35], 2011Phase III461GEM monotherapyOFF; BSC4.8; 2.3---
Oettle et al[36], 2014, CONKO-003Phase III160GEM monotherapyOFF; FF5.9; 3.32.9; 2.0--
Gill et al[37], 2016, PANCREOXPhase III108GEM-based (approximately 75% monotherapy)mFOLFOX6; FU/LV6.1; 9.93.1; 2.913.2; 8.560; 63.8
Wang-Gillam et al[37], 2016, NAPOLI-1Phase III417GEM-based2Nal-IRI; FU/LV; Nal-IRI + FU/LV4.9; 4.2; 6.12.7; 1.5; 3.16; 1; 1644; 24; 52
Chung et al[29], 2018Phase II48GEM-basedmFOLFIRINOX9.05.818.862.5
Tsavaris et al[33], 2005Phase II30GEMOX 50 mg/mq + FU/LV (1-h iv infusion), weekly6.25-23.353.3
Pelzer et al[32], 2009Phase II37GEMOFF5.53.0649
Yoo et al[34], 2009Phase II61GEM-basedmFOLFIRI.3; mFOLFOX3.9; 3.51.9; 1.40; 723; 17
Zaniboni et al[49], 2012Phase II50GEM ± platinoidFOLFIRI53.2836
Chung et al[29], 2018, SWOG S1115Phase II137GEM-basedSelumetinib+ MK-2206; mFOLFOX3.9; 6.71.9; 2.01.7; 822.4; 30.6
Portal et al[22], 2015Prospective cohort57FOLFIRINOXNabGem8.85.117.558
Zaanan et al[47], 2014Prospective cohort46GEM/FOLFIRI.3 in FIRGEM trialFOLFOX4.31.7036
Wainberg et al[45], 2020Meta-analysis454GEM-basedFOLFOX; Nal-IRI6.3; 6.1---
Sonbol et al[51], 2017Meta-analysis895GEM-basedFPOX; FPIRIFPFPIRI vs FP: HR OS 0.7, PFS 0.64; FPOX vs FP: HR OS 1.0, PFS 0.81
Citterio et al[52], 2018Meta-analysis1587GEM-basedFP, OX or IRI-basedMost effective IRI-based regimens (results cannot be translated into the table)
Rahma et al[43], 2013Systematic analysis1503GEM-basedGEM + platinum; FPOXBSC6.0; 5.7; 2.84; 2.9; ---
Petrelli et al[53], 2017Systematic analysis-GEM-basedOX-based; IRI-based5.3; 5.52.9; 2.711.9; 8.741.1; 29.4
Berk et al[48], 2012Comparative85GEM-basedFOLFOX4; XELOX5.8; 4.93.7; 3.717; 1843; 59
Zhang et al[19], 2018Retrospective146FOLFIRINOXNabGem; Gem alone5.69; 3.823.61; 2.51--
Chae et al[21], 2020Retrospective102FOLFIRINOXNabGem9.84.68.573.6
Viaud et al[17], 2017Retrospective96FOLFIRINOXGEM monotherapy3.72.1-40
Gilabert et al[18], 2017Retrospective72FOLFIRINOXGEM monotherapy-2.511-
Pointet et al[38], 2020Retrospective137NabGemFOLFOX; FOLFIRI; FOLFIRINOX3.5; 9.7; 6.12; 6.6; 3.40; 9.5; 6.329.2; 61.9; 50
Lee et al[41], 2020Retrospective120GEM-basedFPOX; FP7.04; 7.432.89; 3.816.4; 5.452.6; 59.5
Neuzillet et al[50], 2012Retrospective63GEM ± platinoidFOLFIRI6.63.07.939.7
Kieler et al[24], 2019Retrospective52GEM-basedNal-IRI + FU/LV6.793.8419.246.2
Table 2 Main ongoing targeted therapy studies (clinicaltrial.gov) for advanced pancreatic adenocarcinoma
Phase of study
Ribociclib plus trametinib; NCT02703571CDK4/6Phase I/II trial, open label single armAdvanced or metastatic pancreatic cancer and KRAS-mutant colorectal cancer
Palbociclib + the PI3K/mTOR inhibitor, gedatolisib; NCT03065062CDK4/6Phase I, open label single armAdvanced squamous cell lung, pancreatic, head and neck and other solid tumours
Abemaciclib in combination with the TGF-β inhibitor galunisertib or other agents; NCT02981342CDK4/6Phase II, open label, randomizedPreviously treated metastatic pancreatic ductal adenocarcinoma
BKM120 + mFOLFOX6; NCT01571024PI3KPhase I, open label, single armAdvanced solid tumours including metastatic pancreatic cancer
Metformin + Gemcitabine + Erlotinib; NCT01210911PI3KPhase II, randomized, placebo controlledLocally advanced or metastatic pancreatic cancer
Capecitabine + Cetuximab + Everolimus; NCT01077986mTORPhase I/II, open label, single armMetastatic pancreatic cancer
Temsirolimus; NCT00075647mTORPhase II, open label, single armLocally advanced or metastatic pancreatic cancer
MK2206 + Fluorouracil + Oxaliplatin + Selumetinib; NCT01658943AktPhase II, open label, randomizedMetastatic pancreatic cancer
RX-0201 + Gemcitabine; NCT01028495AktPhase II, open label, single armMetastatic pancreatic cancer
Gemcitabine ± nimotuzumab; NCT02395016EGFRPhase III, prospective, randomized, controlled, double-blindLocally advanced or metastatic pancreatic cancer
MRTX849 (inhibitor of KRAS G12C) + TNO155 (inhibitor of SHP2); NCT04330664KRASG12CPhase I/II, open label, non-randomizedAdvanced or metastatic cancer with a KRASG12C mutation
AMG 510 Monotherapy; NCT03600883KRASG12CPhase I/II, open label, non-randomizedKRAS p.G12C mutant advanced solid tumours
Gemcitabine + M7824 (TGF-β ligand trap); NCT03451773TGF-βPhase I/II, open label, single armLocally advanced or metastatic pancreatic cancer
FFX vs CPI-613 + mFFX; NCT03504423CPI-613Pase III, open-label randomizedMtastatic adenocarcinoma of the pancreas