Article Figures & Data
Figures
- Figure 1
Kaplan-Meier curves of overall survival (A) and progression-free survival (B) for all patients.
- Figure 2
Kaplan-Meier curves of overall survival (A) and progression-free survival (B) for matched patients.
- Figure 3
Forest plot of overall survival in the selected subgroups.
- Figure 4
Forest plot of progression-free survival in the selected subgroups.
- Figure 5
Schematic of the mechanisms of GS and GnP. For GS, S-1 is an oral derivative of the 5-FU prodrug combined with 2 modulators. The expression of hENT1, the mediator of gemcitabine uptake, is upregulated by 5-FU. For GnP, nab-paclitaxel increases gemcitabine levels by inhibiting the gemcitabine-metabolizing enzyme cytidine deaminase. FT, tegafur; CDHP, gimeracil; Oxo, oteracil.
Tables
Characteristics Overall (n = 300) First-line chemotherapy regimen P value GS (n = 84) GnP (n = 216) Gender 0.324 Male 183 (61.0%) 47 (56.0%) 136 (63.0%) Female 117 (39.0%) 37 (44.0%) 80 (37.0%) Age, median (range), years 61 (32, 83) 63 (38, 83) 60 (32, 77) 0.017 ECOG 0.112 0 156 (52.0%) 48 (57.1%) 108 (50.0%) 1 139 (46.3%) 33 (39.3%) 106 (49.1%) 2 5 (1.7%) 3 (3.6%) 2 (0.9%) BMI, median (range), kg/m2 21.6 (15.0, 35.3) 21.6 (15.0, 27.6) 21.5 (15.6, 35.3) 0.978 Smoking history 0.081 Yes 122 (40.7%) 27 (32.1%) 95 (44.0%) No 178 (59.3%) 57 (67.9%) 121 (56.0%) Drinking history 0.121 Yes 70 (23.3%) 14 (16.7%) 56 (25.9%) No 230 (76.7%) 70 (83.3%) 160 (74.1%) Diabetes history 1.000 Yes 92 (30.7%) 26 (31.0%) 66 (30.6%) No 208 (69.3%) 58 (69.0%) 150 (69.4%) Surgery before chemotherapy 0.742 Yes 48 (16.0%) 12 (14.3%) 36 (16.7%) No 252 (84.0%) 72 (85.7%) 180 (83.3%) CA19-9, median (range), U/mL 418 (0, 400,000) 343 (0, 400,000) 478 (0.3, 86,900) 0.300 Baseline stage 0.492 Locally advanced 111 (37.0%) 28 (33.3%) 83 (38.4%) Metastatic 189 (63.0%) 56 (66.7%) 133 (61.6%) Liver metastases 0.738 Yes 140 (46.7%) 41 (48.8%) 99 (45.8%) No 160 (53.3%) 43 (51.2%) 117 (54.2%) Multiple metastases 0.347 Yes 47 (15.7%) 10 (11.9%) 37 (17.1%) No 253 (84.3%) 74 (88.1%) 179 (82.9%) Items Overall (n = 300) First-line chemotherapy regimen P value GS (n = 84) GnP (n = 216) Best response 0.328 CR 0 0 0 PR 33 (11.0%) 12 (14.3%) 21 (9.7%) SD 196 (65.3%) 56 (66.7%) 140 (64.8%) PD 71 (23.7%) 16 (19.0%) 55 (25.5%) ORR 11.0% 14.3% 9.7% 0.353 DCR 76.3% 81.0% 74.5% 0.307 Change in CA19-9 0.104 Not expressed 53 (17.7%) 20 (23.8%) 33 (15.3%) Declined > 30% 162 (54.0%) 47 (56.0%) 115 (53.2%) Declined ≤ 30% 67 (22.3%) 15 (17.9%) 52 (24.1%) Unknown 18 (6.0%) 2 (2.4%) 16 (7.4%) CR, complete response; DCR, disease control rate; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease.
Variables Univariate analysis Multivariate analysis HR (95% CI) P value HR (95% CI) P value Age, years 0.99 (0.97–1.01) 0.297 - - Gender (male vs. female) 1.01 (0.75–1.38) 0.925 - - ECOG (1 vs. 0) 1.85 (1.37–2.51) < 0.001 1.93 (1.40–2.64) < 0.001 ECOG (2 vs. 0) 0.59 (0.14–2.40) 0.459 0.71 (0.17–2.92) 0.636 BMI, kg/m2 0.98 (0.93–1.03) 0.433 - - Smoking history (yes vs. no) 0.96 (0.70–1.30) 0.771 - - Drinking history (yes vs. no) 0.85 (0.59–1.22) 0.380 - - Diabetes history (yes vs. no) 1.06 (0.77–1.46) 0.718 - - Surgery before chemotherapy (yes vs. no) 0.90 (0.59–1.36) 0.605 - - Baseline stage (metastatic vs. locally advanced) 1.70 (1.23–2.34) 0.001 0.94 (0.57–1.53) 0.789 Baseline CA19-9 level, U/mL 1.00 (1.00–1.00) < 0.001 1.00 (1.00–1.00) < 0.001 Liver metastases (yes vs. no) 1.93 (1.43–2.62) < 0.001 2.12 (1.34–3.34) 0.001 Multiple metastases (yes vs. no) 1.57 (1.05–2.33) 0.026 1.20 (0.78–1.84) 0.419 First-line regimen (GS vs. GnP) 0.63 (0.45–0.89) 0.008 0.69 (0.48–0.97) 0.035 The bold values indicate P < 0.1 in the univariable analysis and P < 0.05 in the multivariable analysis.
Variables Univariate analysis Multivariate analysis HR (95% CI) P value HR (95% CI) P value Age, years 0.99 (0.98–1.01) 0.211 - - Gender (male vs. female) 0.98 (0.76–1.28) 0.894 - - ECOG (1 vs. 0) 1.39 (1.07–1.80) 0.013 1.49 (1.14–1.94) 0.004 ECOG (2 vs. 0) 1.56 (0.64–3.82) 0.332 1.95 (0.79–4.81) 0.148 BMI, kg/m2 0.98 (0.94–1.03) 0.473 - - Smoking history (yes vs. no) 0.94 (0.72–1.22) 0.641 - - Drinking history (yes vs. no) 0.86 (0.63–1.17) 0.343 - - Diabetes history (yes vs. no) 1.26 (0.96–1.66) 0.101 - - Surgery before chemotherapy (yes vs. no) 1.09 (0.77–1.56) 0.619 - - Baseline stage (metastatic vs. locally advanced) 1.80 (1.37–2.37) < 0.001 1.26 (0.84–1.89) 0.259 Baseline CA19-9 level, U/mL 1.00 (1.00–1.00) 0.076 1.00 (1.00–1.00) 0.302 Liver metastases (yes vs. no) 1.98 (1.52–2.57) < 0.001 1.78 (1.22–2.59) 0.003 Multiple metastases (yes vs. no) 1.44 (1.02–2.04) 0.037 1.06 (0.73–1.53) 0.758 First-line regimen (GS vs. GnP) 0.82 (0.62–1.08) 0.157 - - The bold values indicate P < 0.1 in the univariable analysis and P < 0.05 in the multivariable analysis.
First-line chemotherapy regimen GS (n = 82) GnP (n = 190) Overall Second-line 58 (70.7%) 116 (61.1%) Third-line 28 (34.1%) 62 (32.6%) Supportive care 12 (14.6%) 40 (21.1%) Death 3 (3.7%) 6 (3.2%) Unknown 9 (11.0%) 28 (14.7%) Second-line SOX 6 (10.3%) 41 (35.3%) GS 6 (10.3%) 8 (6.9%) GnP 15 (25.9%) 8 (6.9%) Gemcitabine 2 (3.4%) 2 (1.7%) GEMOX 6 (10.3%) 4 (3.4%) FOLFIRINOX 0 (0.0%) 23 (19.8%) FOLFIRI 1 (1.7%) 4 (3.4%) FOLFOX 0 (0.0%) 3 (2.6%) S-1 2 (3.4%) 9 (7.8%) Irinotecan + S-1 0 (0.0%) 2 (1.7%) XELOX 6 (10.3%) 2 (1.7%) PARPi 0 (0.0%) 3 (2.6%) Nab-P 2 (3.4%) 0 (0.0%) Nab-P + S-1 2 (3.4%) 1 (0.9%) Nab-P + oxaliplatin 5 (8.6%) 0 (0.0%) Others 5 (8.6%) 6 (5.2%) FOLFIRI, irinotecan plus fluorouracil and leucovorin; FOLFOX, oxaliplatin plus fluorouracil and leucovorin; GEMOX, gemcitabine plus oxaliplatin; Nab-P, nab-paclitaxel; PARPi, poly ADP-ribose polymerase inhibitor; SOX, S-1 plus oxaliplatin; XELOX, capecitabine plus oxaliplatin.
First-line chemotherapy regimen P value GS (n = 67) GnP (n = 178) Overall 0.329 No 25 (37.3%) 53 (29.8%) Yes 42 (62.7%) 125 (70.2%) Hematologic Leukopenia 0.049 No 57 (85.1%) 128 (71.9%) Yes 10 (14.9%) 50 (28.1%) Neutropenia 0.988 No 35 (52.2%) 95 (53.4%) Yes 32 (47.8%) 83 (46.6%) Thrombocytopenia 0.386 No 60 (89.6%) 167 (93.8%) Yes 7 (10.4%) 11 (6.2%) Anemia 0.839 No 64 (95.5%) 167 (93.8%) Yes 3 (4.5%) 11 (6.2%) Nonhematologic Fatigue 0.839 No 64 (95.5%) 167 (93.8%) Yes 3 (4.5%) 11 (6.2%) Nausea 0.614 No 64 (95.5%) 174 (97.8%) Yes 3 (4.5%) 4 (2.2%) Vomiting 0.896 No 66 (98.5%) 173 (97.2%) Yes 1 (1.5%) 5 (2.8%) Rash 1.000 No 64 (95.5%) 170 (95.5%) Yes 3 (4.5%) 8 (4.5%) Diarrhea 0.893 No 65 (97.0%) 175 (98.3%) Yes 2 (3.0%) 3 (1.7%) Anorexia 1.000 No 64 (95.5%) 170 (95.5%) Yes 3 (4.5%) 8 (4.5%) Bilirubin 0.085 No 63 (94.0%) 176 (98.9%) Yes 4 (6.0%) 2 (1.1%) ALT/AST 1.000 No 66 (98.5%) 175 (98.3%) Yes 1 (1.5%) 3 (1.7%) Hand-foot syndrome 0.611 No 66 (98.5%) 178 (100.0%) Yes 1 (1.5%) 0 (0.0%) Oral mucositis 0.085 No 63 (94.0%) 176 (98.9%) Yes 4 (6.0%) 2 (1.1%) Peripheral neuropathy 0.135 No 67 (100.0%) 169 (94.9%) Yes 0 (0.0%) 9 (5.1%)
