Outcome |
Relative effect 95%CI |
LoD |
Trt. better when |
|
I2 |
k (RCT/OBS)
|
Bayesian probability
|
Overall ROB
|
Publication bias |
Degree of certainty |
Endpoint importance |
Published MA |
efficacy endpoints 00 |
deaths (OS) | 0.77 [0.69, 0.86] | | < 1 | | 0% | 4 studies (4/-) | 100.0 % | some concern | not evaluable | moderate | crucial | - |
deaths (OS) (extension) | 0.75 [0.65, 0.87] | | < 1 | | 0% | 2 studies (2/-) | 100.0 % | some concern | not evaluable | moderate | important | - |
PFS (extension) | 0.79 [0.68, 0.90] | | < 1 | | 0% | 2 studies (2/-) | 100.0 % | some concern | not evaluable | moderate | important | - |
progression or deaths (PFS) | 0.79 [0.71, 0.87] | | < 1 | | 0% | 4 studies (4/-) | 100.0 % | some concern | not evaluable | moderate | important | - |
objective responses (ORR) | 1.20 [0.89, 1.62] | | > 1 | | 60% | 4 studies (4/-) | 88.0 % | some concern | not evaluable | moderate | non important | - |
objective responses (ORR) (extension) | 0.84 [0.56, 1.25] | | > 1 | | 0% | 1 study (1/-) | 19.5 % | NA | not evaluable | | non important | - |
safety endpoints 00 |
AE (any grade) | 2.84 [1.04, 7.75] | | < 1 | | 17% | 3 studies (3/-) | 2.1 % | some concern | not evaluable | moderate | non important | - |
AE (grade 3-4) | 1.06 [0.87, 1.28] | | < 1 | | 0% | 4 studies (4/-) | 27.9 % | some concern | not evaluable | moderate | non important | - |
AE leading to death (grade 5) | 1.03 [0.55, 1.92] | | < 1 | | 57% | 4 studies (4/-) | 46.6 % | some concern | not evaluable | moderate | non important | - |
AE leading to treatment discontinuation (any grade) | 2.19 [1.25, 3.85] | | < 1 | | 67% | 4 studies (4/-) | 0.3 % | some concern | not evaluable | moderate | non important | - |
AE leading to treatment discontinuation (grade 3-4) | 1.00 [0.35, 2.90] | | < 1 | | 0% | 1 study (1/-) | 49.7 % | NA | not evaluable | | non important | - |
SAE (any grade) | 0.93 [0.66, 1.31] | | < 1 | | 35% | 2 studies (2/-) | 66.1 % | some concern | not evaluable | moderate | non important | - |
SAE (grade 3-4) | 0.77 [0.51, 1.15] | | < 1 | | 0% | 1 study (1/-) | 90.3 % | NA | not evaluable | | non important | - |
STRAE (any grade) | 1.07 [0.66, 1.73] | | < 1 | | 70% | 3 studies (3/-) | 38.9 % | some concern | not evaluable | moderate | non important | - |
STRAE (grade 3-4) | 0.82 [0.33, 2.01] | | < 1 | | 86% | 2 studies (2/-) | 66.9 % | some concern | not evaluable | moderate | non important | - |
TRAE (any grade) | 1.14 [0.81, 1.60] | | < 1 | | 0% | 4 studies (4/-) | 22.9 % | some concern | not evaluable | moderate | non important | - |
TRAE (grade 3-4) | 1.00 [0.83, 1.20] | | < 1 | | 1% | 4 studies (4/-) | 51.1 % | some concern | not evaluable | moderate | non important | - |
TRAE leading to death (grade 5) | 1.87 [0.78, 4.48] | | < 1 | | 30% | 4 studies (4/-) | 8.0 % | low | not evaluable | high | non important | - |
TRAE leading to discontinuation (any grade) | 2.13 [0.68, 6.69] | | < 1 | | 81% | 2 studies (2/-) | 9.8 % | some concern | not evaluable | moderate | non important | - |
TRAE leading to discontinuation (grade 3-4) | 2.46 [0.27, 22.20] | | < 1 | | 82% | 2 studies (2/-) | 21.2 % | some concern | not evaluable | moderate | non important | - |
TRAE (grade 3-4) endpoints 00 |
Acute kidney injury TRAE (grade 3-4) | 3.99 [0.18, 89.04] | | < 1 | | 0% | 1 study (1/-) | 19.4 % | NA | not evaluable | | non important | - |
Adrenal insufficiency TRAE (grade 3-4) | 2.72 [0.49, 14.91] | | < 1 | | 0% | 4 studies (4/-) | 12.6 % | some concern | not evaluable | moderate | non important | - |
Alopecia TRAE (grade 3-4) | 0.87 [0.23, 3.30] | | < 1 | | 0% | 4 studies (4/-) | 58.0 % | some concern | not evaluable | moderate | non important | - |
Anaemia TRAE (grade 3-4) | 0.81 [0.56, 1.19] | | < 1 | | 46% | 4 studies (4/-) | 85.8 % | some concern | not evaluable | moderate | non important | - |
Arthritis TRAE (grade 3-4) | 1.00 [0.02, 50.78] | | < 1 | | 0% | 1 study (1/-) | 49.9 % | NA | not evaluable | | non important | - |
Asthenia TRAE (grade 3-4) | 0.81 [0.31, 2.11] | | < 1 | | 0% | 3 studies (3/-) | 67.0 % | some concern | not evaluable | moderate | non important | - |
Colitis TRAE (grade 3-4) | 1.11 [0.15, 8.06] | | < 1 | | 7% | 2 studies (2/-) | 46.0 % | low | not evaluable | high | non important | - |
Constipation TRAE (grade 3-4) | 0.93 [0.17, 5.14] | | < 1 | | 0% | 4 studies (4/-) | 53.3 % | low | not evaluable | high | non important | - |
Decreased appetite TRAE (grade 3-4) | 1.04 [0.26, 4.20] | | < 1 | | 1% | 4 studies (4/-) | 47.6 % | some concern | not evaluable | moderate | non important | - |
Diabetes TRAE (grade 3-4) | 3.33 [0.64, 17.21] | | < 1 | | 0% | 4 studies (4/-) | 7.6 % | some concern | not evaluable | moderate | non important | - |
Diarrhoea TRAE (grade 3-4) | 2.18 [0.92, 5.16] | | < 1 | | 0% | 4 studies (4/-) | 3.9 % | low | not evaluable | high | non important | - |
Fatigue TRAE (grade 3-4) | 1.28 [0.47, 3.44] | | < 1 | | 0% | 4 studies (4/-) | 31.4 % | some concern | not evaluable | moderate | non important | - |
Febrile neutropenia TRAE (grade 3-4) | 0.66 [0.41, 1.06] | | < 1 | | 0% | 3 studies (3/-) | 95.8 % | some concern | not evaluable | moderate | non important | - |
Guillain-Barré syndrome TRAE (grade 3-4) | 1.98 [0.07, 59.51] | | < 1 | | 0% | 1 study (1/-) | 34.9 % | NA | not evaluable | | non important | - |
Hepatitis TRAE (grade 3-4) | 6.04 [0.72, 50.41] | | < 1 | | 0% | 2 studies (2/-) | 4.9 % | low | not evaluable | high | non important | - |
Hyperthyroidism TRAE (grade 3-4) | 1.49 [0.24, 9.14] | | < 1 | | 0% | 4 studies (4/-) | 33.5 % | some concern | not evaluable | moderate | non important | - |
Hypophysitis TRAE (grade 3-4) | 1.24 [0.19, 8.15] | | < 1 | | 0% | 4 studies (4/-) | 41.3 % | some concern | not evaluable | moderate | non important | - |
Hypothyroidism TRAE (grade 3-4) | 1.62 [0.26, 10.10] | | < 1 | | 0% | 4 studies (4/-) | 30.3 % | some concern | not evaluable | moderate | non important | - |
Increased lipase level TRAE (grade 3-4) | 6.52 [1.46, 29.18] | | < 1 | | 0% | 2 studies (2/-) | 0.7 % | some concern | not evaluable | moderate | non important | - |
Infusion-related reactions TRAE (grade 3-4) | 4.02 [0.45, 36.30] | | < 1 | | 0% | 1 study (1/-) | 10.9 % | NA | not evaluable | | non important | - |
Leucopenia TRAE (grade 3-4) | 1.17 [0.81, 1.69] | | < 1 | | 0% | 4 studies (4/-) | 20.1 % | low | not evaluable | high | non important | - |
Myocarditis TRAE (grade 3-4) | 1.32 [0.15, 11.34] | | < 1 | | 0% | 3 studies (3/-) | 40.0 % | some concern | not evaluable | moderate | non important | - |
Myositis TRAE (grade 3-4) | 2.00 [0.07, 60.06] | | < 1 | | 0% | 1 study (1/-) | 34.6 % | NA | not evaluable | | non important | - |
Nausea TRAE (grade 3-4) | 0.59 [0.21, 1.61] | | < 1 | | 0% | 4 studies (4/-) | 84.9 % | some concern | not evaluable | moderate | non important | - |
Nephritis TRAE (grade 3-4) | 1.99 [0.18, 22.08] | | < 1 | | 0% | 2 studies (2/-) | 28.8 % | low | not evaluable | high | non important | - |
Neutropenia TRAE (grade 3-4) | 0.86 [0.69, 1.07] | | < 1 | | 20% | 4 studies (4/-) | 91.6 % | some concern | not evaluable | moderate | non important | - |
Pancreatitis TRAE (grade 3-4) | 0.79 [0.11, 5.62] | | < 1 | | 0% | 2 studies (2/-) | 59.4 % | low | not evaluable | high | non important | - |
Pancytopenia TRAE (grade 3-4) | 0.33 [0.03, 3.17] | | < 1 | | 0% | 1 study (1/-) | 83.1 % | NA | not evaluable | | non important | - |
Paraesthesia TRAE (grade 3-4) | 1.49 [0.11, 19.45] | | < 1 | | 0% | 2 studies (2/-) | 38.1 % | some concern | not evaluable | moderate | non important | - |
Peripheral neuropathy TRAE (grade 3-4) | 3.99 [0.18, 89.04] | | < 1 | | 0% | 1 study (1/-) | 19.4 % | NA | not evaluable | | non important | - |
Pneumonia TRAE (grade 3-4) | 6.02 [0.30, 120.88] | | < 1 | | 0% | 1 study (1/-) | 12.3 % | NA | not evaluable | | non important | - |
Pneumonitis TRAE (grade 3-4) | 1.89 [0.55, 6.53] | | < 1 | | 0% | 4 studies (4/-) | 15.8 % | some concern | not evaluable | moderate | non important | - |
Pruritus TRAE (grade 3-4) | 1.00 [0.06, 16.06] | | < 1 | | 0% | 2 studies (2/-) | 49.9 % | some concern | not evaluable | moderate | non important | - |
Rash TRAE (grade 3-4) | 4.54 [0.71, 28.97] | | < 1 | | 0% | 3 studies (3/-) | 5.5 % | some concern | not evaluable | moderate | non important | - |
Severe skin reaction TRAE (grade 3-4) | 3.81 [0.36, 40.15] | | < 1 | | 0% | 2 studies (2/-) | 13.5 % | low | not evaluable | high | non important | - |
Thrombocytopenia TRAE (grade 3-4) | 0.96 [0.67, 1.38] | | < 1 | | 22% | 4 studies (4/-) | 58.5 % | low | not evaluable | high | non important | - |
Thyroiditis TRAE (grade 3-4) | 1.00 [0.06, 16.06] | | < 1 | | 0% | 2 studies (2/-) | 49.9 % | some concern | not evaluable | moderate | non important | - |
Uveitis TRAE (grade 3-4) | 2.00 [0.07, 60.06] | | < 1 | | 0% | 1 study (1/-) | 34.6 % | NA | not evaluable | | non important | - |
Vomiting TRAE (grade 3-4) | 0.66 [0.24, 1.82] | | < 1 | | 0% | 4 studies (4/-) | 78.6 % | low | not evaluable | high | non important | - |
AE (grade 3-4) endpoints 00 |
Alopecia AE (grade 3-4) | 0.91 [0.24, 3.43] | | < 1 | | 0% | 3 studies (3/-) | 55.4 % | some concern | not evaluable | moderate | non important | - |
Anaemia AE (grade 3-4) | 0.68 [0.43, 1.07] | | < 1 | | 59% | 3 studies (3/-) | 95.2 % | some concern | not evaluable | moderate | non important | - |
Asthenia AE (grade 3-4) | 1.06 [0.53, 2.10] | | < 1 | | 0% | 3 studies (3/-) | 43.8 % | low | not evaluable | high | non important | - |
Back pain AE (grade 3-4) | 1.42 [0.26, 7.77] | | < 1 | | 0% | 3 studies (3/-) | 34.4 % | some concern | not evaluable | moderate | non important | - |
Constipation AE (grade 3-4) | 1.26 [0.24, 6.64] | | < 1 | | 0% | 3 studies (3/-) | 39.2 % | some concern | not evaluable | moderate | non important | - |
Cough AE (grade 3-4) | 1.26 [0.24, 6.64] | | < 1 | | 0% | 3 studies (3/-) | 39.2 % | some concern | not evaluable | moderate | non important | - |
Decreased appetite AE (grade 3-4) | 1.00 [0.27, 3.68] | | < 1 | | 28% | 3 studies (3/-) | 49.9 % | some concern | not evaluable | moderate | non important | - |
Diarrhoea AE (grade 3-4) | 1.32 [0.61, 2.85] | | < 1 | | 0% | 3 studies (3/-) | 24.1 % | some concern | not evaluable | moderate | non important | - |
Dizziness AE (grade 3-4) | 1.00 [0.02, 50.62] | | < 1 | | 0% | 1 study (1/-) | 50.0 % | NA | not evaluable | | non important | - |
Dyspnoea AE (grade 3-4) | 1.28 [0.57, 2.87] | | < 1 | | 0% | 3 studies (3/-) | 27.6 % | some concern | not evaluable | moderate | non important | - |
Fatigue AE (grade 3-4) | 1.31 [0.57, 3.01] | | < 1 | | 0% | 3 studies (3/-) | 26.6 % | some concern | not evaluable | moderate | non important | - |
Febrile neutropenia AE (grade 3-4) | 0.82 [0.49, 1.37] | | < 1 | | 0% | 2 studies (2/-) | 78.1 % | some concern | not evaluable | moderate | non important | - |
Headache AE (grade 3-4) | 1.26 [0.18, 8.99] | | < 1 | | 0% | 3 studies (3/-) | 40.8 % | some concern | not evaluable | moderate | non important | - |
Hypertension AE (grade 3-4) | 7.69 [1.75, 33.81] | | < 1 | | 0% | 2 studies (2/-) | 0.4 % | some concern | not evaluable | moderate | non important | - |
Hyperthyroidism AE (grade 3-4) | 1.49 [0.11, 19.45] | | < 1 | | 0% | 2 studies (2/-) | 38.1 % | some concern | not evaluable | moderate | non important | - |
Hypothyroidism AE (grade 3-4) | 1.00 [0.02, 50.62] | | < 1 | | 0% | 1 study (1/-) | 50.0 % | NA | not evaluable | | non important | - |
Increased Lipase Level AE (grade 3-4) | 1.89 [0.79, 4.52] | | < 1 | | 0% | 2 studies (2/-) | 7.6 % | some concern | not evaluable | moderate | non important | - |
Leucopenia AE (grade 3-4) | 1.16 [0.78, 1.73] | | < 1 | | 0% | 3 studies (3/-) | 23.7 % | some concern | not evaluable | moderate | non important | - |
Nausea AE (grade 3-4) | 0.66 [0.26, 1.68] | | < 1 | | 0% | 3 studies (3/-) | 80.6 % | some concern | not evaluable | moderate | non important | - |
Neutropenia AE (grade 3-4) | 0.88 [0.64, 1.21] | | < 1 | | 54% | 3 studies (3/-) | 78.1 % | some concern | not evaluable | moderate | non important | - |
Peripheral oedema AE (grade 3-4) | 1.00 [0.02, 50.62] | | < 1 | | 0% | 1 study (1/-) | 50.0 % | NA | not evaluable | | non important | - |
Pneumonia AE (grade 3-4) | 1.04 [0.59, 1.82] | | < 1 | | 7% | 3 studies (3/-) | 45.0 % | some concern | not evaluable | moderate | non important | - |
Pruritus AE (grade 3-4) | 1.00 [0.10, 9.65] | | < 1 | | 0% | 3 studies (3/-) | 50.0 % | some concern | not evaluable | moderate | non important | - |
Pyrexia AE (grade 3-4) | 0.67 [0.11, 4.14] | | < 1 | | 0% | 3 studies (3/-) | 66.5 % | some concern | not evaluable | moderate | non important | - |
Rash AE (grade 3-4) | 4.04 [0.62, 26.08] | | < 1 | | 0% | 3 studies (3/-) | 7.2 % | some concern | not evaluable | moderate | non important | - |
Thrombocytopenia AE (grade 3-4) | 0.92 [0.59, 1.42] | | < 1 | | 38% | 3 studies (3/-) | 65.1 % | some concern | not evaluable | moderate | non important | - |
Vomiting AE (grade 3-4) | 0.71 [0.25, 2.03] | | < 1 | | 0% | 3 studies (3/-) | 74.1 % | some concern | not evaluable | moderate | non important | - |