| bevacizumab + capecitabine vs capecitabine | No demonstrated result heart failure (grade 3) by 268% (harmful effect) hypertension (grade 3) by 920% (harmful effect) suggested objective response (ORR) by 72% (not demonstrated) | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| objective response (ORR) | 1.72 [1.23 2.42] | p=0.04 | 0 | 948 | 2 | RIBBON-I (Robert) on top capecitabine,AVF2119g (Miller) cape, | | death (overall survival) | 0.97 [0.58 1.60] | p=1.00 | 0 | 1077 | 2 | RIBBON-I (Robert) on top capecitabine,AVF2119g (Miller) cape, | | progression or death (progression free survival PFS) | 0.81 [0.50 1.32] | p=1.00 | 0 | 1077 | 2 | RIBBON-I (Robert) on top capecitabine,AVF2119g (Miller) cape, | | heart failure (grade 3) | 3.68 [1.06 12.83] | p=0.04 | 0 | 1734 | 2 | RIBBON-I (Robert) on top capecitabine,AVF2119g (Miller) cape, | | arterial/venous thromboembolism (grade 3) | no data | | cardiomyopathy (grade 3) | 1.88 [0.17 20.86] | p=1.00 | 0 | 444 | 1 | AVF2119g (Miller) cape, | | treatment-related deaths | 0.60 [0.18 1.98] | p=1.00 | 0 | 605 | 1 | RIBBON-I (Robert) on top capecitabine, | | permanent discontinuation | 1.00 [0.59 1.68] | p=1.00 | 0 | 605 | 1 | RIBBON-I (Robert) on top capecitabine, | | serious adverse events | 1.28 [0.84 1.95] | p=1.00 | 0 | 605 | 1 | RIBBON-I (Robert) on top capecitabine, | | hypertension (grade 3) | 10.20 [2.44 42.61] | p=0.04 | 0 | 605 | 1 | RIBBON-I (Robert) on top capecitabine, | | gastrointestinal perforation (grade 3) | 0.50 [0.01 25.17] | p=1.00 | 0 | 605 | 1 | RIBBON-I (Robert) on top capecitabine, | | bleeding (grade 3) | 0.50 [0.03 8.00] | p=1.00 | 0 | 605 | 1 | RIBBON-I (Robert) on top capecitabine, |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients |
| bevacizumab + docetaxel vs docetaxel | No demonstrated result | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| objective response (ORR) | no data | | death (overall survival) | 1.01 [0.81 1.25] | p=1.00 | 0 | 471 | 2 | AVADO (Miles) 15mg ,AVADO (Miles) 7.5mg, | | progression or death (progression free survival PFS) | no data | | heart failure (grade 3) | no data | | permanent discontinuation | no data | | treatment-related deaths | no data | | serious adverse events | no data | | hypertension (grade 3) | no data | | arterial/venous thromboembolism (grade 3) | no data | | gastrointestinal perforation (grade 3) | no data | | bleeding (grade 3) | no data | | cardiomyopathy (grade 3) | no data |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients |
| bevacizumab + methotrexate vs methotrexate | No demonstrated result | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| objective response (ORR) | 3.09 [0.60 15.81] | p=1.00 | 0 | 55 | 1 | Burstein, | | death (overall survival) | no data | | progression or death (progression free survival PFS) | no data | | heart failure (grade 3) | no data | | permanent discontinuation | no data | | treatment-related deaths | no data | | serious adverse events | no data | | hypertension (grade 3) | no data | | gastrointestinal perforation (grade 3) | no data | | bleeding (grade 3) | no data | | cardiomyopathy (grade 3) | no data | | arterial/venous thromboembolism (grade 3) | 1.85 [0.07 47.70] | p=1.00 | 0 | 55 | 1 | Burstein, |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients |
| bevacizumab + paclitaxel vs paclitaxel | No demonstrated result | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| objective response (ORR) | 1.24 [0.70 2.20] | p=1.00 | 0 | 191 | 1 | Martin bevacizumab, | | death (overall survival) | no data | | progression or death (progression free survival PFS) | 0.79 [0.33 1.90] | p=1.00 | 0 | 191 | 1 | Martin bevacizumab, | | heart failure (grade 3) | no data | | arterial/venous thromboembolism (grade 3) | no data | | gastrointestinal perforation (grade 3) | no data | | bleeding (grade 3) | no data | | cardiomyopathy (grade 3) | no data | | treatment-related deaths | 0.31 [0.03 3.03] | p=1.00 | 0 | 185 | 1 | Martin bevacizumab, | | permanent discontinuation | 1.70 [0.79 3.68] | p=1.00 | 0 | 185 | 1 | Martin bevacizumab, | | serious adverse events | 0.75 [0.38 1.46] | p=1.00 | 0 | 185 | 1 | Martin bevacizumab, | | hypertension (grade 3) | 6.49 [0.78 53.85] | p=1.00 | 0 | 185 | 1 | Martin bevacizumab, |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients |
| bevacizumab + taxanes vs taxanes | No demonstrated result serious adverse events by 49% (harmful effect) permanent discontinuation by 47% (harmful effect) hypertension (grade 3) by 1498% (harmful effect) bleeding (grade 3) by 721% (harmful effect) suggested objective response (ORR) by 70% (not demonstrated) suggested progression or death (progression free survival PFS) by 37% (not demonstrated) | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| objective response (ORR) | 1.70 [1.29 2.22] | p=0.04 | 0 | 994 | 2 | E2100 (Miller),RIBBON-I (Robert) on top Tax or anthra, | | death (overall survival) | 0.92 [0.58 1.45] | p=1.00 | 0 | 1344 | 2 | E2100 (Miller),RIBBON-I (Robert) on top Tax or anthra, | | progression or death (progression free survival PFS) | 0.63 [0.41 0.98] | p=0.04 | 0 | 1344 | 2 | E2100 (Miller),RIBBON-I (Robert) on top Tax or anthra, | | heart failure (grade 3) | 7.58 [0.94 60.96] | p=1.00 | 0 | 711 | 1 | E2100 (Miller), | | serious adverse events | 1.49 [1.00 2.21] | p=0.04 | 0 | 615 | 1 | RIBBON-I (Robert) on top Tax or anthra, | | cardiomyopathy (grade 3) | no data | | treatment-related deaths | 0.78 [0.29 2.07] | p=1.00 | 0 | 1326 | 2 | E2100 (Miller),RIBBON-I (Robert) on top Tax or anthra, | | permanent discontinuation | 1.47 [1.08 2.02] | p=0.04 | 0 | 1326 | 2 | E2100 (Miller),RIBBON-I (Robert) on top Tax or anthra, | | hypertension (grade 3) | 15.98 [4.48 57.08] | p=0.04 | 0 | 1326 | 2 | E2100 (Miller),RIBBON-I (Robert) on top Tax or anthra, | | arterial/venous thromboembolism (grade 3) | 1.52 [0.49 4.68] | p=1.00 | 0 | 711 | 1 | E2100 (Miller), | | gastrointestinal perforation (grade 3) | 3.05 [0.53 17.69] | p=1.00 | 0 | 1326 | 2 | E2100 (Miller),RIBBON-I (Robert) on top Tax or anthra, | | bleeding (grade 3) | 8.21 [1.04 65.09] | p=0.04 | 0 | 1326 | 2 | E2100 (Miller),RIBBON-I (Robert) on top Tax or anthra, |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients |
| bevacizumav + CT vs CT alone | No demonstrated result | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| objective response (ORR) | 1.33 [0.91 1.96] | p=1.00 | 0 | 541 | 1 | RIBBON-2 (Brufsky), | | death (overall survival) | 0.90 [0.46 1.77] | p=1.00 | 0 | 684 | 1 | RIBBON-2 (Brufsky), | | progression or death (progression free survival PFS) | 0.78 [0.43 1.43] | p=1.00 | 0 | 684 | 1 | RIBBON-2 (Brufsky), | | heart failure (grade 3) | 4.34 [0.23 81.02] | p=1.00 | 0 | 679 | 1 | RIBBON-2 (Brufsky), | | permanent discontinuation | no data | | treatment-related deaths | no data | | serious adverse events | no data | | hypertension (grade 3) | no data | | arterial/venous thromboembolism (grade 3) | no data | | gastrointestinal perforation (grade 3) | no data | | bleeding (grade 3) | no data | | cardiomyopathy (grade 3) | no data |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients |
First line therapy: 6 trials - E2100 (Miller) - AVADO (Miles) 15mg - RIBBON-I (Robert) on top capecitabine - RIBBON-I (Robert) on top Tax or anthra - AVADO (Miles) 7.5mg - Martin bevacizumab
| bevacizumab + capecitabine vs capecitabine | No demonstrated result hypertension (grade 3) by 920% (harmful effect) | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| objective response (ORR) | 1.50 [0.98 2.30] | p=1.00 | 0 | 486 | 1 | RIBBON-I (Robert) on top capecitabine, | | death (overall survival) | 0.85 [0.40 1.82] | p=1.00 | 0 | 615 | 1 | RIBBON-I (Robert) on top capecitabine, | | progression or death (progression free survival PFS) | 0.68 [0.34 1.34] | p=1.00 | 0 | 615 | 1 | RIBBON-I (Robert) on top capecitabine, | | heart failure (grade 3) | 6.91 [0.90 52.70] | p=1.00 | 0 | 1220 | 1 | RIBBON-I (Robert) on top capecitabine, | | arterial/venous thromboembolism (grade 3) | no data | | cardiomyopathy (grade 3) | no data | | treatment-related deaths | 0.60 [0.18 1.98] | p=1.00 | 0 | 605 | 1 | RIBBON-I (Robert) on top capecitabine, | | permanent discontinuation | 1.00 [0.59 1.68] | p=1.00 | 0 | 605 | 1 | RIBBON-I (Robert) on top capecitabine, | | serious adverse events | 1.28 [0.84 1.95] | p=1.00 | 0 | 605 | 1 | RIBBON-I (Robert) on top capecitabine, | | hypertension (grade 3) | 10.20 [2.44 42.61] | p=0.04 | 0 | 605 | 1 | RIBBON-I (Robert) on top capecitabine, | | gastrointestinal perforation (grade 3) | 0.50 [0.01 25.17] | p=1.00 | 0 | 605 | 1 | RIBBON-I (Robert) on top capecitabine, | | bleeding (grade 3) | 0.50 [0.03 8.00] | p=1.00 | 0 | 605 | 1 | RIBBON-I (Robert) on top capecitabine, |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients |
| bevacizumab + docetaxel vs docetaxel | No demonstrated result | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| objective response (ORR) | no data | | death (overall survival) | 1.01 [0.81 1.25] | p=1.00 | 0 | 471 | 2 | AVADO (Miles) 15mg ,AVADO (Miles) 7.5mg, | | progression or death (progression free survival PFS) | no data | | heart failure (grade 3) | no data | | permanent discontinuation | no data | | treatment-related deaths | no data | | serious adverse events | no data | | hypertension (grade 3) | no data | | arterial/venous thromboembolism (grade 3) | no data | | gastrointestinal perforation (grade 3) | no data | | bleeding (grade 3) | no data | | cardiomyopathy (grade 3) | no data |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients |
| bevacizumab + paclitaxel vs paclitaxel | No demonstrated result | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| objective response (ORR) | 1.24 [0.70 2.20] | p=1.00 | 0 | 191 | 1 | Martin bevacizumab, | | death (overall survival) | no data | | progression or death (progression free survival PFS) | 0.79 [0.33 1.90] | p=1.00 | 0 | 191 | 1 | Martin bevacizumab, | | heart failure (grade 3) | no data | | arterial/venous thromboembolism (grade 3) | no data | | gastrointestinal perforation (grade 3) | no data | | bleeding (grade 3) | no data | | cardiomyopathy (grade 3) | no data | | treatment-related deaths | 0.31 [0.03 3.03] | p=1.00 | 0 | 185 | 1 | Martin bevacizumab, | | permanent discontinuation | 1.70 [0.79 3.68] | p=1.00 | 0 | 185 | 1 | Martin bevacizumab, | | serious adverse events | 0.75 [0.38 1.46] | p=1.00 | 0 | 185 | 1 | Martin bevacizumab, | | hypertension (grade 3) | 6.49 [0.78 53.85] | p=1.00 | 0 | 185 | 1 | Martin bevacizumab, |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients |
| bevacizumab + taxanes vs taxanes | No demonstrated result serious adverse events by 49% (harmful effect) permanent discontinuation by 47% (harmful effect) hypertension (grade 3) by 1498% (harmful effect) bleeding (grade 3) by 721% (harmful effect) suggested objective response (ORR) by 70% (not demonstrated) suggested progression or death (progression free survival PFS) by 37% (not demonstrated) | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| objective response (ORR) | 1.70 [1.29 2.22] | p=0.04 | 0 | 994 | 2 | E2100 (Miller),RIBBON-I (Robert) on top Tax or anthra, | | death (overall survival) | 0.92 [0.58 1.45] | p=1.00 | 0 | 1344 | 2 | E2100 (Miller),RIBBON-I (Robert) on top Tax or anthra, | | progression or death (progression free survival PFS) | 0.63 [0.41 0.98] | p=0.04 | 0 | 1344 | 2 | E2100 (Miller),RIBBON-I (Robert) on top Tax or anthra, | | heart failure (grade 3) | 7.58 [0.94 60.96] | p=1.00 | 0 | 711 | 1 | E2100 (Miller), | | serious adverse events | 1.49 [1.00 2.21] | p=0.04 | 0 | 615 | 1 | RIBBON-I (Robert) on top Tax or anthra, | | cardiomyopathy (grade 3) | no data | | treatment-related deaths | 0.78 [0.29 2.07] | p=1.00 | 0 | 1326 | 2 | E2100 (Miller),RIBBON-I (Robert) on top Tax or anthra, | | permanent discontinuation | 1.47 [1.08 2.02] | p=0.04 | 0 | 1326 | 2 | E2100 (Miller),RIBBON-I (Robert) on top Tax or anthra, | | hypertension (grade 3) | 15.98 [4.48 57.08] | p=0.04 | 0 | 1326 | 2 | E2100 (Miller),RIBBON-I (Robert) on top Tax or anthra, | | arterial/venous thromboembolism (grade 3) | 1.52 [0.49 4.68] | p=1.00 | 0 | 711 | 1 | E2100 (Miller), | | gastrointestinal perforation (grade 3) | 3.05 [0.53 17.69] | p=1.00 | 0 | 1326 | 2 | E2100 (Miller),RIBBON-I (Robert) on top Tax or anthra, | | bleeding (grade 3) | 8.21 [1.04 65.09] | p=0.04 | 0 | 1326 | 2 | E2100 (Miller),RIBBON-I (Robert) on top Tax or anthra, |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients |
Second line therapy: 2 trials - AVF2119g (Miller) cape - RIBBON-2 (Brufsky)
| bevacizumab + capecitabine vs capecitabine | No demonstrated result suggested objective response (ORR) by 117% (not demonstrated) | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| objective response (ORR) | 2.17 [1.25 3.77] | p=0.04 | 0 | 462 | 1 | AVF2119g (Miller) cape, | | death (overall survival) | 1.07 [0.54 2.11] | p=1.00 | 0 | 462 | 1 | AVF2119g (Miller) cape, | | progression or death (progression free survival PFS) | 0.98 [0.49 1.96] | p=1.00 | 0 | 462 | 1 | AVF2119g (Miller) cape, | | heart failure (grade 3) | 2.52 [0.52 12.24] | p=1.00 | 0 | 514 | 1 | AVF2119g (Miller) cape, | | permanent discontinuation | no data | | treatment-related deaths | no data | | serious adverse events | no data | | hypertension (grade 3) | no data | | arterial/venous thromboembolism (grade 3) | no data | | gastrointestinal perforation (grade 3) | no data | | bleeding (grade 3) | no data | | cardiomyopathy (grade 3) | 1.88 [0.17 20.86] | p=1.00 | 0 | 444 | 1 | AVF2119g (Miller) cape, |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients |
| bevacizumav + CT vs CT alone | No demonstrated result | | Endpoint | TE [95% CI] | p val | I2 | n | k | trials |
|---|
| objective response (ORR) | 1.33 [0.91 1.96] | p=1.00 | 0 | 541 | 1 | RIBBON-2 (Brufsky), | | death (overall survival) | 0.90 [0.46 1.77] | p=1.00 | 0 | 684 | 1 | RIBBON-2 (Brufsky), | | progression or death (progression free survival PFS) | 0.78 [0.43 1.43] | p=1.00 | 0 | 684 | 1 | RIBBON-2 (Brufsky), | | heart failure (grade 3) | 4.34 [0.23 81.02] | p=1.00 | 0 | 679 | 1 | RIBBON-2 (Brufsky), | | permanent discontinuation | no data | | treatment-related deaths | no data | | serious adverse events | no data | | hypertension (grade 3) | no data | | arterial/venous thromboembolism (grade 3) | no data | | gastrointestinal perforation (grade 3) | no data | | bleeding (grade 3) | no data | | cardiomyopathy (grade 3) | no data |
TE: treatment effect; CI: confidence interval; k: nulmber of trials; n: total number of patients |
