Review Article

Clinical Outcomes of Specific Immunotherapy in Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis

Table 1

Clinical information from eligible trials used in the meta-analysis.

Author, journal (year) [Ref]CountryAgeSex (M/F)Number of pts. (case/control)Study designEnrollment periodTumor stageSpecific immunotherapy armControl armSpecific immunotherapy courseLength of follow-up

Asahara et al., J Transl Med (2013) [8]JapanMedian (range) 61.3 (33–80) years66/46112 (31/81)Retrospective case-control study2009.3–2010.2UnknownKIF20A-66 HLA-A24-restricted peptide + chemotherapyChemotherapy1.0 or 3.0 mg/body peptide × 8 in a 56 days cycle + 1.0 or 3.0 mg/m2 gemcitabine per 2 weeksUnknown
Bernhardt et al., Br J Cancer (2006) [9]NorwayRange: 40–72 years26/2248 (26/22)Phase I/II case-control study2000.9–2003.3UnknownTelomerase peptide vaccineNegative peptide3 injections in week 1 and 1 weekly injection in weeks 2, 3, 4, 6, and 1010–575 days (survival days from start of treatment)
Brett et al., J Clin Oncol (2002) [10]UKMedian (range) 62.95 (44–79) years24/630Phase II self-control studyUnknownII, III, IVAnti-gastrin-17 antibodyUnknown3 doses of 100 μg or 250 μg of G17DT on weeks 0, 2, and 616 weeks
Cai et al., Chinese Journal of Cancer Biotherapy (2013) [11]ChinaMedian (range) 64 (30–75) years13/1124Self-control study2011.7–2012.5III, IVDC pulsed with antigens of PANC-1 cells + CIKUnknown1 × 106 DC × 4 + 1 × 106 CIK × 34 weeks after first treatment to 16.7 months
Chawla et al., Mol Ther (2010) [12]USAMedian (range) 64 (50–83) years7/613 (7/6)Phase I/II case-control study2007.10–2009.1UnknownPositive Rexin-G vaccineNegative vaccine1-2 × 1011 cfu Rexin-G × 120–12 months
Endo et al., J Hepatobiliary Pancreat Sci (2012) [13]JapanMean age 62 ± 8.1 years13/1124 (9/15)Phase I case-control study2003.11–2007.7IA, IIA, IIB, IVDC + OK432OK4321.0 × 108 DC + 0.1 mL OK4320.7–6.1 years
Gjertsen et al., Int J Cancer (2001) [14]NorwayRange: 35–77 years19/1837 (17/20)Phase I/II case-control study1996.11–1998.11UnknownK-ras peptide vaccination + GM-CSFNegative peptide100 μg (single mutant ras peptide or a mixture of 4 mutant ras peptides) × 4 + 40 μg GM-CSF × 43–6 months after first injection to 2 years
Kameshima et al., Cancer Sci (2013) [15]JapanRange 50–80 years3/36Self-control study2005.12–2010.11UnknownSurvivin-2B80-88 peptide + IFA + α-interferonUnknown(1 mg/1 mL peptide + 1 mL IFA) × 4 + 3,000 IU α-interferon × 12Unknown
Koido et al., Clin Cancer Res (2014) [16]JapanRange 39–73 years7/411Phase I self-control study2011.8–2013.1IVDC pulsed with multiple WT-1 peptides + chemotherapyUnknown1 × 107 DC/WT-1 cells/dose × 5 + 1000 mg/m2  gemcitabine × 5800 days after first injection
Kondo et al., Anticancer Res (2008) [17]JapanRange 51–84 years14/620Self-control study2001–2006III, IVDCs pulsed with MUC1 peptide + CTLs stimulated by MUC1-expressing cellsUnknown (1.1 × 107 to 3.1 × 108 MUC1-DCs + 5.0 × 108 to 6.8 × 109) × 2 to 15 timesUnknown
Kubuschok et al., Hum Gene Ther (2012) [18]GermanyRange 48–66 years4/37Self-control study1997–2000II, IIImuRas-LCLUnknown5 × 106 muRas-LCL × 87–52 weeks
Le et al., J Immunother (2013) [19]USAMedian (range) 62 (44–77) years21/930 (15/15)Phase Ib, randomized study2009.3–2010.12II, III, IVIpilimumab + GVAXIpilimumab10 mg/kg ipilimumab + 2.5 × 108 cells of GVAX0–30 months
Le et al., J Clin Oncol (2015) [20]USAMedian (range) 63 (45–87) years53/3790 (61/29)Multicenter, randomized, case-control phase II trial2011.9–2012-11UnknownCy/GVAX plus CRS-207Cy/GVAX(200 mg/m2 cy + 2.5 × 108 cells GVAX) × 6 + 1 × 109 colony-forming units CRS-207 × 6600 days after first treatment
Liu, Chin J Clinicians (2012) [21]ChinaMedian (range) 61 (42–76) years27/2350 (25/25)Randomized, case-control study2010.6–2011.12I, II, III, IVDC pulsed with tumor cells lysates + CIK + chemotherapyChemotherapy2 × 109 DC-CIK cells × 6 + 600 mg/m2 5-FUUnknown
Liu et al., Nanjing yi ke da xue xue bao (2010) [22]ChinaRange 48–79 years17/1330 (15/15)Randomized, case-control studyUnknownIII, IVDC pulsed with tumor cells lysates + CIK + chemotherapyChemotherapyDC × 4 + 1 g/m2 chemotherapy × 187 days after therapy
Middleton et al., Lancet Oncol (2014) [23]UKRange 55–69 years608/4541062 (704/358)Multicenter, open-label, phase III randomized control trial2007.3–2011.3UnknownTelomerase peptide vaccine GV1001 + gemcitabine and capecitabineGemcitabine, capecitabine1000 mg/m2 gemcitabine × 6 + 830 mg/m2  capecitabine × 2 + GV1001Followed up for a median of 6.0 months
Nishida et al., J Immunother (2014) [24]JapanMedian (range) 60 (41–75) years17/1532Phase I self-control study2008–2010UnknownWT-1 peptides vaccine + gemcitabineUnknown1000 mg/m2 gemcitabine × 6 + 0.3 to 3.0 mg WT-1 vaccine × 430 months
Picozzi et al., Eur J Cancer (2015) [25]USARange 39–80 years33/2558 (29/29)Phase Ib case-control study2102.6–2013.2Unknown90Y-clivatuzumab tetraxetan (anti-MUC5ac monoclonal antibody) + gemcitabine90Y-clivatuzumab tetraxetan6.5 mCi/m2 Y-clivatuzumab tetraxetan × 3 ± 200 mg/m2 gemcitabine × 412 months after first injection
Qiu et al., Int J Clin Oncol (2013) [26]ChinaMean (range) age 60.1 ± 8.4 (44–90) years12/214Phase I self-control study2004.3–2009.2III, IVDC pulsed with α-Gal expressing cancer cell lysate + CIKUnknown(2 × 109 cells–10 × 109 cells) (DCs + CIKs)/injection × 1–5 times24 months after first injection
Sultana et al., BMC Cancer (2009) [27]UKMedian (range) 60 (47–67) yearsUnknown19Randomized phase II self-control trial2003.2–2005.7IVa, IVbAnti-carcinoembryonic antigen I131KAb201 antibodiesUnknown50 mCi–75 mCi KAb 201 via either the intra-arterial or intravenous delivery route90 days posttreatment
Suzuki et al., J Immunother (2014) [28]JapanMedian (range) 62 (48–74) years4/59Nonrandomized, open-label, phase I self-control studyUnknownIII, IVKIF20A-10-66 peptide + gemcitabineUnknown0.5–3 mg/body KIF20A-10-66 peptide × 4 + 1000 mg/m2  gemcitabine × 394–366 days
Wen et al., Xiandai zhongxiyi jiehe zazhi (2013) [29]ChinaRange 49–78 years33/2760 (30/30)Randomized, case-control study2008.3–2011.3UnknownDC pulsed with tumor cells lysates + CIK + chemotherapyChemotherapy2 × 109 DC-CIK cells × 6 + 600 mg/m2 5-FU2–26 months
Yanagimoto et al., Oncol Rep (2010) [30]JapanMedian (range) 64 (48–80) years13/821Nonrandomized, open-label, phase II self-control study2006.9–2008.3IVa, IVbPPV + gemcitabineUnknown3 mg/peptide were administered weekly + 1000 mg/m2  gemcitabine per week for 3 weeks3–24 months
Yutani et al., Oncol Rep (2013) [31]JapanMedian (range) 61 (44–78) years27/1441Open-label phase II self-control study2008.11–2011.3IVa, IVbPPVUnknown4 peptides (3 mg/each peptide) administered once a week for 6 consecutive weeks Over 800 days
Zhang, Zhongguo xian dai yi xue za zhi (2014) [32]ChinaMean range 58.2 ± 5.2 (48–78) years33/2760 (30/30)Randomized, case-control study2010.1–2012.6I, II, III, IVDC pulsed with tumor cells lysates + CIK + chemotherapyChemotherapy2 × 109 DC-CIK cells × 4 + 15 mg/kg 5-FU × 4 Over 3 years

DC, dendritic cell; CIK, cytokine-induced killer cell; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFA, incomplete Freund’s adjuvant; WT-1, Wilms’ tumor-1; MUC1, Mucin 1; LCL; lymphoblastoid cell lines; GVAX, GM-CSF cell-based vaccines; α-Gal, alpha-galactosyl; PPV, personalized peptide vaccination; CRS-207, human mesothelin; ipilimumab, anti-CTLA-4 antibody.