Chemotherapy versus best supportive care for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies
Intervention: chemotherapy

Control: best supportive care alone

Overall survival

HR 0.37
(0.24 to 0.55)

184
(3 studies)

⊕⊕⊕⊝
moderate¹

Weighted average of median survival durations from included studies

Time to progression

HR 0.31
(0.22 to 0.43)

144
(2 studies)

⊕⊕⊕⊝
moderate¹

Weighted average of median survival durations from included studies

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Combination versus single‐agent chemotherapy for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies
Intervention: combination

Control: single‐agent chemotherapy

Overall survival

HR 0.84
(0.79 to 0.89)

4447
(23)

⊕⊕⊕⊝
moderate¹

Weighted average of median survival durations from included studies

Tumour response

OR 2.30
(1.94 to 2.72)

2833
(18)

⊕⊕⊕⊕
high¹

Time to progression

HR 0.69
(0.55 to 0.87)

720
(4)

⊕⊕⊕⊝
moderate¹

Weighted average of median survival durations from included studies

Treatment‐related death

OR 1.64
(0.83 to 3.24)

3876
(18)

⊕⊕⊝⊝
moderate²

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; OR: Odds ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

5‐FU/cisplatin/anthracycline combinations versus 5‐FU/cisplatin combinations (without anthracyclines) for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies
Intervention: 5‐FU/cisplatin/anthracycline combinations

Control: 5‐FU/cisplatin combinations (without anthracyclines)

Overall survival

HR 0.74
(0.61 to 0.89)

579
(4)

⊕⊕⊕⊝
moderate¹

Weighted average of median survival durations from included studies

Tumour response

OR 2.86
(1.14 to 7.16)

78
(1)

⊕⊕⊝⊝
low²

Time to progression

HR 0.62
(0.38 to 0.98)

78
(1)

⊕⊕⊝⊝
low²

Median survival durations from the only included study

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; OR: Odds ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

5‐FU/cisplatin/anthracycline combinations versus 5‐FU/anthracycline combinations (without cisplatin) for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies
Intervention: 5‐FU/cisplatin/anthracycline combinations

Control: 5‐FU/cisplatin combinations (without anthracyclines)

Overall survival

HR 0.82
(0.73 to 0.92)

1147
(7)

⊕⊕⊝⊝
low^1,2

Weighted average of median survival durations from included studies

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Irinotecan versus non‐irinotecan‐containing regimens for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies
Intervention: irinotecan

Control: non‐irinotecan‐containing regimens

Overall survival

HR 0.87
(0.80 to 0.95)

2135
(10 studies)

⊕⊕⊕⊝
moderate¹

Weighted average of median survival durations from included studies

Overall survival ‐ Substitutive comparisons

HR 0.87

(0.75 to 1.00)

826
(6 studies)

⊕⊕⊕⊝
moderate¹

Weighted average of median survival durations from included studies

Overall survival ‐ Additive comparisons

HR 0.88
(0.76 to 1.03)

500
(3 studies)

⊕⊕⊝⊝
low^1,2

Weighted average of median survival durations from included studies

Overall survival ‐ Other comparisons

HR 0.87
(0.76 to 1.00)

809
(2 studies)

⊕⊝⊝⊝
very low^1,3

Weighted average of median survival durations from included studies

Tumour response

OR 1.72

(1.24 to 2.40)

1266
(10 studies)

⊕⊕⊝⊝
low³

Tumour response ‐ Substitutive comparisons

OR 1.53

(0.93 to 2.50)

756
(6 studies)

⊕⊕⊝⊝
low³

Tumour response ‐ Additive comparisons

OR 2.18

(1.25 to 3.80)

345
(3 studies)

⊕⊕⊝⊝
low^1,2

Tumour response ‐ Other comparisons

OR 1.87
(0.89 to 3.91)

165
(2 studies)

⊕⊝⊝⊝
very low^1,2,4

Progression‐free survival

HR 0.76

(0.69 to 0.84)

1640
(7 studies)

⊕⊕⊕⊕
high

Weighted average of median survival durations from included studies

Progression‐free survival ‐ Substitutive comparison

HR 0.85

(0.72 to 1.00)

741
(5 studies)

⊕⊕⊕⊝
moderate¹

Weighted average of median survival durations from included studies

Progression‐free survival ‐ Additive comparisons

HR 0.51
(0.33 to 0.77)

90
(1)

⊕⊕⊕⊝
moderate²

Median survival durations from the only included study

Progression‐free survival ‐ Other comparisons

HR 0.74

(0.66 to 0.84)

809
(2 studies)

⊕⊕⊕⊕
high

Weighted average of median survival durations from included studies

Treatment‐related death

OR 0.88

(0.23 to 3.32)

1979
(9 studies)

⊕⊕⊝⊝
low^2,4

Treatment discontinuation due to toxicity

OR 1.00

(0.46 to 2.20)

1979
(9 studies)

⊕⊝⊝⊝
very low^2,3

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; OR: Odds ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Docetaxel versus non‐docetaxel‐containing regimens for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies
Intervention: docetaxel

Control: non‐docetaxel‐containing regimens

Overall survival

HR 0.86

(0.78 to 0.95)

2001
(8 studies)

⊕⊕⊕⊕
high

Weighted average of median survival durations from included studies

Overall survival ‐ Substitutive comparisons

HR 1.05

(0.87 to 1.27)

479
(3 studies)

⊕⊕⊕⊝
moderate¹

Weighted average of median survival durations from included studies

Overall survival ‐ Additive comparisons

HR 0.80

(0.71 to 0.91)

1466
(4 studies)

⊕⊕⊕⊝
moderate²

Weighted average of median survival durations from included studies

Overall survival ‐ Other comparisons

HR 0.80

(0.46 to 1.39)

56
(1 study)

⊕⊝⊝⊝
very low^1,2,3

Median survival durations from the only included study

Tumour response

OR 1.37

(1.03 to 1.83)

1820
(9 studies)

⊕⊕⊕⊝
moderate⁴

Tumour response ‐ Substitutive comparison

OR 1.03

(0.71 to 1.50)

525
(4 studies)

⊕⊕⊕⊝
moderate¹

Tumour response ‐ Additive comparison

OR 1.83

(1.45 to 2.32)

1235
(4 studies)

⊕⊕⊕⊕
high

Tumour response ‐ Other comparison

OR 0.33

(0.12 to 0.96)

60
(1 study)

⊕⊝⊝⊝
very low^1,3

Time to progression

HR 1.06

(0.85 to 1.32)

360
(2 studies)

⊕⊝⊝⊝
very low^1,2,3

Weighted average of median survival durations from included studies

Progression‐free survival

HR 0.76

(0.63 to 0.91)

1498
(5 studies)

⊕⊕⊕⊝
moderate⁴

Weighted average of median survival durations from included studies

Progression‐free survival ‐ Substitutive comparisons

HR 1.15

(0.77 to 1.72)

119
(1 study)

⊕⊝⊝⊝
very low^1,2,3

Median survival durations from the only included study

Progression‐free survival ‐ Additive comparison

HR 0.70

(0.61 to 0.81)

1323
(3 studies)

⊕⊕⊕⊕
high

Weighted average of median survival durations from included studies

Progression‐free survival ‐ Other comparison

HR 0.94

(0.55 to 1.60)

56
(1 study)

⊕⊝⊝⊝
very low^1,3

Median survival durations from the only included study

Treatment‐related death

OR 1.10
(0.55 to 2.20)

2113
(7 studies)

⊕⊕⊕⊝
moderate¹

Treatment discontinuation due to toxicity

OR 0.81

(0.53 to 1.25)

1066
(5 studies)

⊕⊕⊝⊝
low^1,4

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; OR: Odds ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Capecitabine versus 5‐FU‐containing regimens for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies with approximately half of all participants enrolled from Asian countries
Intervention: capecitabine

Control: 5‐FU‐containing regimens

Overall Survival

HR 0.94

(0.79 to 1.11)

732
(5 studies)

⊕⊕⊕⊝
moderate¹

Weighted average of median survival durations from included studies

Tumour response

OR 0.85

(0.40 to 1.79)

636
(4 studies)

⊕⊝⊝⊝
very low^2,3

Time to progression

HR 0.72

(0.47 to 1.12)

85
(1 study)

⊕⊝⊝⊝
very low^1,3

Median survival durations from the only included study

Progression‐free survival

HR 0.98

(0.77 to 1.23)

647
(4 studies)

⊕⊝⊝⊝
very low^1,3,4

Weighted average of median survival durations from included studies

Treatment‐related death

OR 1.88

(0.23 to 15.15)

481
(2 studies)

⊕⊝⊝⊝
very low^1,2,3

Treatment discontinuation due to toxicity

OR 0.99

(0.56 to 1.77)

311
(1 study)

⊕⊕⊝⊝
low³

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; OR: Odds ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Oxaliplatin versus the same regimen including cisplatin for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies with the majority of participants enrolled in Asia
Intervention: oxaliplatin‐containing regimen

Control: the same regimen including cisplatin

Overall Survival

HR 0.81

(0.67 to 0.98)

1105
(5 studies)

⊕⊕⊝⊝
low^1,2

Weighted average of median survival durations from included studies

Tumour response

OR 1.38

(1.08 to 1.76)

1081
(5 studies)

⊕⊕⊕⊝
moderate¹

Progression‐free survival

HR 0.88

(0.66 to 1.19)

1034
(4 studies)

⊕⊕⊝⊝
low^1,3

Weighted average of median survival durations from included studies

Treatment‐related death

OR 0.47

(0.17 to 1.30)

1132
(5 studies)

⊕⊕⊝⊝
low^1,3

Treatment discontinuation due to toxicity

OR 0.97

(0.44 to 2.13)

970
(3 studies)

⊕⊝⊝⊝
very low^1,2,3

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; OR: Odds ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Taxane‐platinum‐fluoropyrimidine combinations versus taxane‐platinum (without fluoropyrimidine) for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies, without Asian representation
Intervention: taxane‐platinum‐fluoropyrimidine combinations

Control: taxane‐platinum (without fluoropyrimidine)

Overall survival

OR 0.86
(0.71 to 1.06)

482
(3 studies)

⊕⊝⊝⊝
very low^1,2

Weighted average of median survival durations from included studies

Tumour response

OR 2.08
(1.37 to 3.15)

482
(3 studies)

⊕⊕⊝⊝
low^1,3

Progression‐free survival

OR 0.74
(0.59 to 0.93)

482
(3 studies)

⊕⊕⊕⊝
moderate¹

Weighted average of median survival durations from included studies

Treatment‐related death

OR 1.95
(0.73 to 5.17)

482
(3 studies)

⊕⊝⊝⊝
very low^1,4

Treatment discontinuation due to toxicity

OR 1.71
(0.79 to 3.69)

234
(2 studies)

⊕⊝⊝⊝
very low^1,4

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; OR: Odds ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

S‐1 versus 5‐FU‐containing regimens for advanced gastric cancer

Patient or population: people with advanced gastric cancer
Settings: outpatient clinics participating in international multicentre studies, mostly performed in Asia
Intervention: S‐1‐containing regimens

Control: 5‐FU‐containing regimens

Overall Survival

HR 0.91
(0.83 to 1.00)

1793
(4 studies)

⊕⊕⊕⊕
high

Weighted average of median survival durations from included studies

Tumour response

OR 1.73
(1.01 to 2.94)

1753
(7 studies)

⊕⊝⊝⊝
very low^1,2

Progression‐free survival

HR 0.85
(0.70 to 1.04)

1942
(4 studies)

⊕⊕⊝⊝
low¹

Weighted average of median survival durations from included studies

Time‐to treatment failure

HR 0.88
(0.76 to 1.01)

1818
(5 studies)

⊕⊕⊝⊝
low¹

Weighted average of median survival durations from included studies

Treatment‐related deaths

OR 0.56
(0.30 to 1.06)

1962
(4 studies)

⊕⊕⊕⊝
moderate²

Treatment discontinuation due to toxicity

OR 0.85
(0.63 to 1.13)

1726
(3 studies)

⊕⊕⊕⊕
high

*For time‐to‐event outcomes, e.g. overall survival, the assumed and corresponding risks were obtained by calculating the weighted average of the median survival durations reported in included studies. For dichotomous outcomes, the assumed and corresponding risks (and their 95% confidence interval) are based on proportions of events in the control and intervention groups respectively.
CI: Confidence interval; OR: Odds ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.