Summary of findings for the main comparison. Summary of findings: Molecular‐targeted therapy plus chemotherapy compared to chemotherapy alone for people with advanced gastric cancer.
| Molecular‐targeted therapy plus chemotherapy compared to chemotherapy alone for people with advanced gastric cancer | ||||||
| Patient or population: people with advanced gastric cancer Setting: hospital Intervention: molecular‐targeted therapy plus chemotherapy Comparison: chemotherapy alone | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Assumed risk with chemotherapy alone | Corresponding risk with molecular‐target therapy plus chemotherapy | |||||
| Overall survival | Study population:12 month mortality rate | HR 0.92 (0.80 to 1.05) | 3843 participants (10 RCTs) |
⊕⊕⊝⊝ LOW 1,2 | Assumed risk calculated based on 12 months overall mortality rates (extracted from corresponding Kaplan‐Meier curves) observed in the control arms of the included trials (53.6%). We could not explain variation in the effect by subgroup analyses examining the type of molecular targeted agent or tumour type. |
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| 536 per 1000 | 507 per 1000 (459 to 553) | |||||
| Progression‐free survival | Study population: 6 month progression‐free survival rate | HR 0.90 (0.78 to 1.04) | 4014 participants (11 RCTs) |
⊕⊕⊝⊝ LOW 2,3,4 | Assumed risk calculated based on 6‐month progression rate (extracted from corresponding Kaplan‐Meier curves) observed in the control arms of the included trials (55.5%) We could not explain variation in the effect by subgroup analyses examining the type of molecular targeted agent or tumour type. |
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| 555 per 1000 | 517 per 1000 (432 to 577) | |||||
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Quality of life (change from baseline in EORTC QOL30 global health status scale) Duration of follow‐up: Median follow‐up differed between treatment groups (28 months with molecular‐targeted therapy and 23 months in control group) |
Higher change scores were obtained for chemotherapy‐alone group (MD 10 ± 33.9 SD) than molecular‐targeted therapy plus chemotherapy group (MD 0.0 ± 28.1 SD), but the results are based on a very small number of participants and the confidence interval is wide | 53 participants (1 RCT) |
⊕⊝⊝⊝ VERY LOW 5,6 | |||
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Overall response rate Duration of follow‐up: varied considerably between studies (the median follow‐up time ranged from 5.3 months to 28.5 months) |
Study population | OR 1.24 (1.00 to 1.55) | 3723 (11 RCTs) | ⊕⊕⊝⊝ LOW 2,4 | ||
| 365 per 1000 | 417 per 1000 (365 to 472) | |||||
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Adverse event (any) Duration of follow‐up: varied considerably between studies (the median follow‐up time ranged from 5.3 months to 28.5 months) |
Study population | OR 2.23 (1.27 to 3.92) | 2290 (5 RCTs) | ⊕⊕⊕⊝ MODERATE 7 | ||
| 962 per 1000 | 983 per 1000 (971 to 990) | |||||
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Severe adverse event (grade ≥ 3 ) Duration of follow‐up: varied considerably between studies (the median follow‐up time ranged from 5.3 months to 28.5 months) |
Study population | OR 1.19 (1.03 to 1.37) | 3800 (8 RCTs) | ⊕⊕⊕⊝ MODERATE8 | ||
| 669 per 1000 | 707 per 1000 (676 to 735) | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio; HR: Hazard ratio. | ||||||
| GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect | ||||||
1Downgraded one level due to imprecision: the confidence interval obtained under both the primary and sensitivity analysis for risk of bias includes potentially meaningful differences with either intervention.
2Downgraded one level due to inconsistency: The size and direction of effect varied across the studies (significant heterogeneity was detected).
3Removal of studies at high risk of performance bias reduced the statistical heterogeneity and increased the effect size, so we did not downgrade for risk of bias.
4Downgraded one level due to imprecision: the confidence interval around the effect includes both meaningful benefit and little or no effect of molecular‐targeted therapy.
5Downgraded two levels due to imprecision: effect was estimated based on results from 53 participants and the confidence interval includes appreciable harm and little/no effect.
6Downgraded one level due to serious risk of bias: open‐label study was at high risk of performance bias for this outcome.
7Downgraded one level due to risk of bias (selective reporting bias): three included studies did not provide data on this outcome, and three others had no summary data for meta‐analysis.
8Downgraded one level due to risk of bias (performance bias): removing studies at high risk bias due to lack of blinding resulted in a more imprecise effect suggesting that the results may have been sensitive to the exclusion of open‐label studies.