Table III.
Meta-analyses of conventional systemic and locoregional therapy in locally advanced, advanced, or metastatic pancreatic cancer.
| Study | Trials | Analytic arm(s) | Main end point(s) | Findings | (Refs.) |
|---|---|---|---|---|---|
| Bernstein et al 2014 | 6 RCTs | CRT vs. CT | OS | HR 0.88 (95% CI, 0.67–1.15; P=0.351) | (100) |
| Chan et al 2014 | 16 RCTs | Bayesian analysis | OS | Best regimen probability 83% FOLFIRINOX, | (114) |
| 11% G-nab, 3% G + erlotinib | |||||
| Gresham et al 2014 | 23 RCTs | Combo-CT vs. G alone | OS | Combo-CT superior to G alone | (115) |
| (including FOLFIRINOX and G-nab) | |||||
| Li et al 2014 | 8 RCTs | G+fluorouracil drugs vs. G alone | OS, ORR | G + fluorouracil drugs significantly improved OS, | (67) |
| ORR compared to G alone | |||||
| Petrelli et al 2014 | 29 RCTs | Combo-CT vs. G alone | OS | HR 0.87 (95% CI, 0.81–0.93; P<0.0001) | (116) |
| Zhang et al 2014 | 3 RCTs, 1 RS | G-based CRT vs. G alone | OS | HR 0.84 (95% CI, 0.53–1.34; P=0.48) | (101) |
| Chen et al 2013 | 15 RCTs | A: CRT vs. RT | 6-, 12- and 18-months OS | A: 6-, 12- and 18-months (all P<0.01) | (99) |
| B: CRT vs. CT | B: 6-, 12- and 18-months (all P>0.05) | ||||
| Ciliberto et al 2013 | 34 RCTs | G-combo vs. G alone | OS | HR 0.93 (95% CI, 0.89–0.97; P=0.001) | (73) |
| Yang et al 2013 | 5 RCTs, 9 PS, 2 RS | G + erlotinib | PFS, OS | PFS 2–9.6 months; OS 5–12.5 months | (110) |
| Sun et al 2012 | 26 RCTs | G-combo vs. G alone | 1-year OS | RR 0.90 (95% CI, 0.82–0.99; P=0.04) | (66) |
| Hu et al 2011 | 35 RCTs | G-combo vs. G alone | OS, PFS | OS OR 1.15 (P=0.011); PFS OR 1.27 (P<0.001) | (65) |
| Zhu et al 2011 | 3 RCTs, 1 RS | G-based CRT vs. F-based CRT | 12-months OS | G-based CRT superior to F-based CRT, | (102) |
| 12-months OS RR 1.54 (95% CI, 1.05–2.26; P=0.03) | |||||
| Xie et al 2010 | 18 RCTs | Subgroup analysis of | 6-months OS | G-C 6-months OS RR 0.85 (P=0.04); G-Ox 6-months OS | (72) |
| 5 G-combo regimens | RR 0.80 (P=0.001) | ||||
| Cunningham et al 2009 | 3 RCTs | G-C vs. G alone | OS | HR 0.86 (95% CI, 0.75–0.98; P=0.02) | (71) |
| Huguet et al 2009 | 2 MAs, 13 RCTs, | A: CRT vs. BSC or RT | OS | A: CRT superior to BSC or RT alone | (98) |
| 2 NRTs | B: CRT vs. CT | B: CRT not superior to CT | |||
| Heinemann et al 2008 | 15 RCTs | G-combo vs. G alone | OS | HR 0.91 (95% CI, 0.85–0.97; P=0.004) | (70) |
| Sultana et al 2008 | 11 RCTs | Indirect analysis of 4 G-combo regimens | OS | No significant difference in survival | (82) |
| Sultana et al 2008 | 51 RCTs | A: F-combo vs. F alone | PFS/TTP | A: TTP HR 1.02 (95% CI, 0.85–1.23) | (62) |
| B: G-combo vs. G alone | B: PFS HR 0.78 (95% CI, 0.70–0.88) | ||||
| Banu et al 2007 | 23 RCTs | G-D vs. G alone | OS | 12-months RRR 4% (95% CI, 1–7); | (69) |
| 18-months RRR 2% (95% CI, 1–4), P<0.05 in both | |||||
| Bria et al 2007 | 20 RCTs | G-combo vs. G alone | OS | No significant difference in survival | (64) |
| Heinemann et al 2007 | 2 RCTs | G-P vs. G alone | OS, PFS | OS HR 0.81 (P=0.031); PFS HR 0.75 (P=0.0030) | (68) |
| Sultana et al 2007 | 51 RCTs | A: CT vs. BSC | OS | A: HR 0.64 (95% CI, 0.42–0.98) | (58) |
| B: F-combo vs. F alone | B: HR 0.94 (95% CI, 0.82–1.08) | ||||
| Sultana et al 2007 | 11 RCTs | A: CRT vs. RT | OS | A: HR 0.69 (95% CI, 0.51–0.94) | (97) |
| B: CRT followed by CT vs. CT | B: HR 0.79 (95% CI, 0.32–1.95) | ||||
| Xie et al 2006 | 6 RCTs | G-DDP vs. G alone | OS, CBR | No significant difference in survival or CBR | (61) |
| Xie et al 2006 | 22 RCTs | G-combo vs. G alone | 1-year survival and | 1-year RD 3% (95% CI, 0.01–0.05; P=0.01); | (63) |
| 6-months PFS rate | 6-months PFS rate RD 7% (95% CI, 0.04–0.10; P<0.00001) | ||||
| Liang et al 2005 | 19 RCTs | G-combo vs. G alone | 6-months survival | 6-months survival rate RD 4% (P=0.02); | (60) |
| and PFS rate | 6-months PFS rate RD 10% (P=0.00001) | ||||
| Fung et al 2003 | 43 RCTs | CT (F-based) vs. BSC | OS | CT (F-based) superior to BSC alone | (108) |
RCTs, randomized controlled trials; CRT, chemoradiotherapy; CT, chemotherapy; OS, overall survival; HR, hazard ratio; CI, confidence interval; FOLFIRINOX, 5-FU, leucovorin, irinotecan, and oxaliplatin; G-nab, gemcitabine + nab-paclitaxel; Combo-CT, combination chemotherapy; G, gemcitabine; ORR, overall response rate; RS, retrospective study; RT, radiotherapy; G-combo, gemcitabine-based combination chemotherapy; PS, prospective study; PFS, progression-free survival; RR, risk ratio; OR, odds ratio; F, 5-fluorouracil (5-FU); G-C, gemcitabine + capecitabine; G-Ox, gemcitabine + oxaliplatin; MAs, meta-analyses; NRTs, non-randomized trials; BSC, best supportive care; F-combo, 5-FU-based combination chemotherapy; TTP, Time to progression; G-D, gemcitabine-based doublets; RRR, relative risk reduction; G-P, gemcitabine + platinum; G-DDP, gemcitabine + cisplatin; CBR, clinical benefit rate; RD, risk difference (risk in gemcitabine-based combination group - risk in gemcitabine alone).