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) | 0.65 [0.52, 0.83] | | < 1 | | 69% | 5 studies (5/-) | 100.0 % | some concern | not evaluable | moderate | crucial | - |
deaths (OS) (extension) | 0.67 [0.55, 0.82] | | < 1 | | 68% | 4 studies (4/-) | 100.0 % | some concern | not evaluable | moderate | important | - |
PFS (extension) | 0.61 [0.38, 1.00] | | < 1 | | 95% | 4 studies (4/-) | 97.5 % | some concern | not evaluable | moderate | important | - |
progression or deaths (PFS) | 0.62 [0.42, 0.91] | | < 1 | | 93% | 5 studies (5/-) | 99.3 % | some concern | not evaluable | moderate | important | - |
objective responses (ORR) | 2.19 [1.28, 3.74] | | > 1 | | 89% | 5 studies (5/-) | 99.8 % | some concern | not evaluable | moderate | non important | - |
objective responses (ORR) (extension) | 2.10 [1.04, 4.21] | | > 1 | | 91% | 4 studies (4/-) | 98.1 % | some concern | not evaluable | moderate | non important | - |
safety endpoints 00 |
AE (any grade) | 1.52 [0.52, 4.45] | | < 1 | | 0% | 2 studies (2/-) | 22.1 % | low | not evaluable | high | non important | - |
AE (grade 3-4) | 1.01 [0.79, 1.28] | | < 1 | | 0% | 2 studies (2/-) | 47.9 % | low | not evaluable | high | non important | - |
AE leading to death (grade 5) | 1.23 [0.76, 1.97] | | < 1 | | 0% | 2 studies (2/-) | 19.9 % | low | not evaluable | high | non important | - |
AE leading to treatment discontinuation (any grade) | 2.24 [1.59, 3.15] | | < 1 | | 0% | 2 studies (2/-) | 0.0 % | low | not evaluable | high | non important | - |
AE leading to treatment discontinuation (grade 3-4) | 2.07 [1.43, 2.99] | | < 1 | | 0% | 2 studies (2/-) | 0.0 % | low | not evaluable | high | non important | - |
STRAE (any grade) | 1.76 [0.55, 5.64] | | < 1 | | 76% | 2 studies (2/-) | 17.1 % | some concern | not evaluable | moderate | non important | - |
STRAE (grade 3-4) | 2.09 [0.38, 11.45] | | < 1 | | 83% | 2 studies (2/-) | 19.9 % | some concern | not evaluable | moderate | non important | - |
TRAE (any grade) | 0.31 [0.15, 0.65] | | < 1 | | 74% | 3 studies (3/-) | 99.9 % | some concern | not evaluable | moderate | non important | - |
TRAE (grade 3-4) | 0.53 [0.22, 1.29] | | < 1 | | 90% | 3 studies (3/-) | 91.9 % | some concern | not evaluable | moderate | non important | - |
TRAE leading to death (grade 5) | 1.00 [0.56, 1.77] | | < 1 | | 0% | 4 studies (4/-) | 50.7 % | some concern | not evaluable | moderate | non important | - |
TRAE leading to discontinuation (any grade) | 0.87 [0.62, 1.21] | | < 1 | | 0% | 3 studies (3/-) | 79.6 % | some concern | not evaluable | moderate | non important | - |
TRAE leading to discontinuation (grade 3-4) | 1.09 [0.74, 1.61] | | < 1 | | 0% | 3 studies (3/-) | 32.7 % | some concern | not evaluable | moderate | non important | - |
TRAE (grade 3-4) endpoints 00 |
Acute kidney injury TRAE (grade 3-4) | 4.32 [0.19, 97.73] | | < 1 | | 0% | 1 study (1/-) | 18.2 % | NA | not evaluable | | non important | - |
Adrenal insufficiency TRAE (grade 3-4) | 1.24 [0.16, 9.82] | | < 1 | | 0% | 2 studies (2/-) | 41.9 % | low | not evaluable | high | non important | - |
Alopecia TRAE (grade 3-4) | 0.19 [0.01, 2.53] | | < 1 | | 17% | 2 studies (2/-) | 89.4 % | some concern | not evaluable | moderate | non important | - |
Anaemia TRAE (grade 3-4) | 0.14 [0.02, 0.86] | | < 1 | | 88% | 3 studies (3/-) | 98.3 % | some concern | not evaluable | moderate | non important | - |
Arthralgia TRAE (grade 3-4) | 0.97 [0.02, 48.81] | | < 1 | | 0% | 1 study (1/-) | 50.7 % | NA | not evaluable | | non important | - |
Asthenia TRAE (grade 3-4) | 0.29 [0.08, 1.05] | | < 1 | | 0% | 1 study (1/-) | 97.0 % | NA | not evaluable | | non important | - |
Blood creatinine increased TRAE (grade 3-4) | 0.68 [0.05, 8.86] | | < 1 | | 0% | 2 studies (2/-) | 61.6 % | some concern | not evaluable | moderate | non important | - |
Colitis TRAE (grade 3-4) | 3.64 [0.78, 16.97] | | < 1 | | 0% | 3 studies (3/-) | 5.0 % | some concern | not evaluable | moderate | non important | - |
Constipation TRAE (grade 3-4) | 1.00 [0.10, 9.63] | | < 1 | | 0% | 3 studies (3/-) | 50.1 % | some concern | not evaluable | moderate | non important | - |
Decreased appetite TRAE (grade 3-4) | 0.47 [0.17, 1.27] | | < 1 | | 0% | 3 studies (3/-) | 93.1 % | some concern | not evaluable | moderate | non important | - |
Diabetes TRAE (grade 3-4) | 1.40 [0.13, 15.46] | | < 1 | | 0% | 2 studies (2/-) | 39.4 % | low | not evaluable | high | non important | - |
Diarrhoea TRAE (grade 3-4) | 2.81 [0.84, 9.40] | | < 1 | | 0% | 3 studies (3/-) | 4.7 % | some concern | not evaluable | moderate | non important | - |
Dizziness TRAE (grade 3-4) | 1.05 [0.02, 53.86] | | < 1 | | 0% | 1 study (1/-) | 49.0 % | NA | not evaluable | | non important | - |
Dysgeusia TRAE (grade 3-4) | 1.01 [0.06, 16.31] | | < 1 | | 0% | 2 studies (2/-) | 49.7 % | some concern | not evaluable | moderate | non important | - |
Fatigue TRAE (grade 3-4) | 0.48 [0.17, 1.36] | | < 1 | | 7% | 3 studies (3/-) | 91.6 % | some concern | not evaluable | moderate | non important | - |
Febrile neutropenia TRAE (grade 3-4) | 2.12 [0.07, 64.42] | | < 1 | | 0% | 1 study (1/-) | 33.5 % | NA | not evaluable | | non important | - |
Hepatitis TRAE (grade 3-4) | 7.53 [0.96, 58.84] | | < 1 | | 0% | 2 studies (2/-) | 2.8 % | some concern | not evaluable | moderate | non important | - |
Hyperthyroidism TRAE (grade 3-4) | 1.05 [0.16, 6.92] | | < 1 | | 0% | 4 studies (4/-) | 48.0 % | some concern | not evaluable | moderate | non important | - |
Hypophysitis TRAE (grade 3-4) | 2.21 [0.31, 15.58] | | < 1 | | 0% | 3 studies (3/-) | 21.3 % | some concern | not evaluable | moderate | non important | - |
Hypothyroidism TRAE (grade 3-4) | 1.50 [0.26, 8.82] | | < 1 | | 0% | 4 studies (4/-) | 32.6 % | some concern | not evaluable | moderate | non important | - |
Increase AST TRAE (grade 3-4) | 1.64 [0.38, 7.03] | | < 1 | | 0% | 2 studies (2/-) | 25.2 % | some concern | not evaluable | moderate | non important | - |
Increased ALT TRAE (grade 3-4) | 1.64 [0.59, 4.55] | | < 1 | | 0% | 2 studies (2/-) | 17.3 % | some concern | not evaluable | moderate | non important | - |
Increased lacrimation (TRAE grade 3-4) | 1.05 [0.02, 53.86] | | < 1 | | 0% | 1 study (1/-) | 49.0 % | NA | not evaluable | | non important | - |
Infusion-related reactions TRAE (grade 3-4) | 0.47 [0.11, 2.06] | | < 1 | | 0% | 4 studies (4/-) | 84.0 % | some concern | not evaluable | moderate | non important | - |
Leucopenia TRAE (grade 3-4) | 0.28 [0.01, 11.52] | | < 1 | | 64% | 2 studies (2/-) | 74.5 % | some concern | not evaluable | moderate | non important | - |
Myalgia TRAE (grade 3-4) | 1.94 [0.06, 57.80] | | < 1 | | 0% | 1 study (1/-) | 35.4 % | NA | not evaluable | | non important | - |
Myocarditis TRAE (grade 3-4) | 1.94 [0.06, 57.80] | | < 1 | | 0% | 1 study (1/-) | 35.4 % | NA | not evaluable | | non important | - |
Myositis TRAE (grade 3-4) | 0.70 [0.04, 11.17] | | < 1 | | 0% | 2 studies (2/-) | 60.0 % | low | not evaluable | high | non important | - |
Nausea TRAE (grade 3-4) | 0.24 [0.03, 1.65] | | < 1 | | 16% | 3 studies (3/-) | 92.5 % | some concern | not evaluable | moderate | non important | - |
Nephritis TRAE (grade 3-4) | 3.10 [0.49, 19.65] | | < 1 | | 0% | 3 studies (3/-) | 11.6 % | some concern | not evaluable | moderate | non important | - |
Neutropenia TRAE (grade 3-4) | 0.10 [0.00, 2.04] | | < 1 | | 80% | 3 studies (3/-) | 93.1 % | some concern | not evaluable | moderate | non important | - |
Pancreatitis TRAE (grade 3-4) | 1.65 [0.23, 11.94] | | < 1 | | 0% | 3 studies (3/-) | 31.1 % | some concern | not evaluable | moderate | non important | - |
Pancytopenia TRAE (grade 3-4) | 0.52 [0.02, 15.84] | | < 1 | | 0% | 1 study (1/-) | 64.4 % | NA | not evaluable | | non important | - |
Peripheral neuropathy TRAE (grade 3-4) | 0.10 [0.01, 1.76] | | < 1 | | 0% | 1 study (1/-) | 94.1 % | NA | not evaluable | | non important | - |
Peripheral oedema TRAE (grade 3-4) | 1.05 [0.02, 53.86] | | < 1 | | 0% | 1 study (1/-) | 49.0 % | NA | not evaluable | | non important | - |
Peripheral sensory neuropathy TRAE (grade 3-4) | 0.08 [0.00, 1.43] | | < 1 | | 0% | 1 study (1/-) | 95.5 % | NA | not evaluable | | non important | - |
Pneumonia TRAE (grade 3-4) | 2.12 [0.07, 64.42] | | < 1 | | 0% | 1 study (1/-) | 33.5 % | NA | not evaluable | | non important | - |
Pneumonitis TRAE (grade 3-4) | 3.39 [0.74, 15.55] | | < 1 | | 55% | 4 studies (4/-) | 5.9 % | some concern | not evaluable | moderate | non important | - |
Pruritus TRAE (grade 3-4) | 2.35 [0.21, 26.88] | | < 1 | | 0% | 2 studies (2/-) | 24.7 % | some concern | not evaluable | moderate | non important | - |
Pyrexia TRAE (grade 3-4) | 0.97 [0.02, 49.41] | | < 1 | | 0% | 1 study (1/-) | 50.5 % | NA | not evaluable | | non important | - |
Rash TRAE (grade 3-4) | 3.75 [0.39, 35.67] | | < 1 | | 0% | 2 studies (2/-) | 12.6 % | some concern | not evaluable | moderate | non important | - |
Sepsis TRAE (grade 3-4) | 2.12 [0.07, 64.42] | | < 1 | | 0% | 1 study (1/-) | 33.5 % | NA | not evaluable | | non important | - |
Severe skin reaction TRAE (grade 3-4) | 2.84 [0.68, 11.82] | | < 1 | | 46% | 4 studies (4/-) | 7.6 % | some concern | not evaluable | moderate | non important | - |
Stomatitis TRAE (grade 3-4) | 0.45 [0.06, 3.24] | | < 1 | | 0% | 3 studies (3/-) | 78.6 % | some concern | not evaluable | moderate | non important | - |
Thrombocytopenia TRAE (grade 3-4) | 0.21 [0.03, 1.28] | | < 1 | | 48% | 3 studies (3/-) | 95.4 % | some concern | not evaluable | moderate | non important | - |
Thyroiditis TRAE (grade 3-4) | 0.78 [0.08, 7.49] | | < 1 | | 0% | 3 studies (3/-) | 58.6 % | some concern | not evaluable | moderate | non important | - |
Vomiting TRAE (grade 3-4) | 0.76 [0.13, 4.47] | | < 1 | | 0% | 3 studies (3/-) | 61.8 % | some concern | not evaluable | moderate | non important | - |
AE (grade 3-4) endpoints 00 |
hepatitis (Autoimmune) AE (grade 3-4) | 10.24 [0.56, 188.30] | | < 1 | | 0% | 1 study (1/-) | 6.1 % | NA | not evaluable | | non important | - |
Alopecia AE (grade 3-4) | 0.33 [0.03, 3.22] | | < 1 | | 0% | 1 study (1/-) | 82.7 % | NA | not evaluable | | non important | - |
Anaemia AE (grade 3-4) | 0.87 [0.58, 1.29] | | < 1 | | 36% | 2 studies (2/-) | 75.5 % | low | not evaluable | high | non important | - |
Arthralgia AE (grade 3-4) | 2.03 [0.37, 11.17] | | < 1 | | 0% | 1 study (1/-) | 20.9 % | NA | not evaluable | | non important | - |
Asthenia AE (grade 3-4) | 1.08 [0.36, 3.25] | | < 1 | | 63% | 2 studies (2/-) | 44.3 % | low | not evaluable | high | non important | - |
Colitis AE (grade 3-4) | 2.04 [0.50, 8.23] | | < 1 | | 0% | 1 study (1/-) | 16.0 % | NA | not evaluable | | non important | - |
Constipation AE (grade 3-4) | 1.04 [0.26, 4.17] | | < 1 | | 0% | 2 studies (2/-) | 47.9 % | low | not evaluable | high | non important | - |
Cough AE (grade 3-4) | 0.64 [0.12, 3.26] | | < 1 | | 0% | 2 studies (2/-) | 70.6 % | low | not evaluable | high | non important | - |
Decreased appetite AE (grade 3-4) | 1.51 [0.53, 4.30] | | < 1 | | 0% | 2 studies (2/-) | 21.9 % | low | not evaluable | high | non important | - |
Diarrhoea AE (grade 3-4) | 1.83 [0.93, 3.61] | | < 1 | | 0% | 2 studies (2/-) | 4.1 % | low | not evaluable | high | non important | - |
Dyspnoea AE (grade 3-4) | 0.97 [0.27, 3.47] | | < 1 | | 35% | 2 studies (2/-) | 52.0 % | low | not evaluable | high | non important | - |
Epistaxis AE (grade 3-4) | 1.01 [0.02, 50.94] | | < 1 | | 0% | 1 study (1/-) | 49.9 % | NA | not evaluable | | non important | - |
Fatigue AE (grade 3-4) | 1.37 [0.48, 3.87] | | < 1 | | 59% | 2 studies (2/-) | 27.9 % | low | not evaluable | high | non important | - |
Hyperthyroidism AE (grade 3-4) | 2.02 [0.07, 60.40] | | < 1 | | 0% | 1 study (1/-) | 34.5 % | NA | not evaluable | | non important | - |
Hypophysitis AE (grade 3-4) | 4.05 [0.18, 90.23] | | < 1 | | 0% | 1 study (1/-) | 19.1 % | NA | not evaluable | | non important | - |
Hypothyroidism AE (grade 3-4) | 2.02 [0.07, 60.40] | | < 1 | | 0% | 1 study (1/-) | 34.5 % | NA | not evaluable | | non important | - |
Infusion-related reaction AE (grade 3-4) | 4.07 [0.45, 36.67] | | < 1 | | 0% | 1 study (1/-) | 10.7 % | NA | not evaluable | | non important | - |
Lacrimation increased AE (grade 3-4) | 0.50 [0.01, 25.20] | | < 1 | | 0% | 1 study (1/-) | 63.4 % | NA | not evaluable | | non important | - |
Myalgia AE (grade 3-4) | 2.02 [0.18, 22.43] | | < 1 | | 0% | 1 study (1/-) | 28.5 % | NA | not evaluable | | non important | - |
Nausea AE (grade 3-4) | 0.92 [0.42, 2.03] | | < 1 | | 0% | 2 studies (2/-) | 57.8 % | low | not evaluable | high | non important | - |
Neutropenia AE (grade 3-4) | 1.08 [0.71, 1.66] | | < 1 | | 46% | 2 studies (2/-) | 35.6 % | low | not evaluable | high | non important | - |
Peripheral neuropathy AE (grade 3-4) | 1.52 [0.25, 9.15] | | < 1 | | 0% | 1 study (1/-) | 32.6 % | NA | not evaluable | | non important | - |
Peripheral oedema AE (grade 3-4) | 1.00 [0.03, 29.86] | | < 1 | | 0% | 1 study (1/-) | 50.1 % | NA | not evaluable | | non important | - |
Pneumonitis AE (grade 3-4) | 3.07 [0.61, 15.32] | | < 1 | | 0% | 1 study (1/-) | 8.7 % | NA | not evaluable | | non important | - |
Pyrexia AE (grade 3-4) | 1.00 [0.18, 5.51] | | < 1 | | 0% | 2 studies (2/-) | 49.8 % | low | not evaluable | high | non important | - |
Rash AE (grade 3-4) | 1.17 [0.30, 4.56] | | < 1 | | 0% | 1 study (1/-) | 41.3 % | NA | not evaluable | | non important | - |
Severe skin reactions AE (grade 3-4) | 3.04 [0.31, 29.44] | | < 1 | | 0% | 1 study (1/-) | 17.0 % | NA | not evaluable | | non important | - |
Thrombocytopenia AE (grade 3-4) | 1.11 [0.70, 1.77] | | < 1 | | 0% | 2 studies (2/-) | 33.0 % | low | not evaluable | high | non important | - |
Thyroiditis AE (grade 3-4) | 2.02 [0.07, 60.40] | | < 1 | | 0% | 1 study (1/-) | 34.5 % | NA | not evaluable | | non important | - |
Vomiting AE (grade 3-4) | 0.57 [0.08, 3.98] | | < 1 | | 66% | 2 studies (2/-) | 71.3 % | low | not evaluable | high | non important | - |