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) | 0.82 [0.71, 0.94] | | < 1 | | 64% | 8 studies (8/-) | 99.8 % | some concern | not evaluable | moderate | crucial | - |
deaths (OS) (extension) | 0.74 [0.64, 0.87] | | < 1 | | 34% | 3 studies (3/-) | 100.0 % | some concern | not evaluable | moderate | important | - |
PFS (extension) | 0.73 [0.49, 1.10] | | < 1 | | 94% | 3 studies (3/-) | 93.2 % | some concern | not evaluable | moderate | important | - |
progression or deaths (PFS) | 0.83 [0.68, 1.01] | | < 1 | | 87% | 8 studies (8/-) | 96.9 % | some concern | not evaluable | moderate | important | - |
objective responses (ORR) | 1.14 [0.90, 1.44] | | > 1 | | 68% | 8 studies (8/-) | 86.0 % | some concern | not evaluable | moderate | non important | - |
objective responses (ORR) (extension) | 1.42 [0.92, 2.18] | | > 1 | | 68% | 3 studies (3/-) | 94.3 % | some concern | not evaluable | moderate | non important | - |
safety endpoints 00 |
AE (any grade) | 0.49 [0.28, 0.86] | | < 1 | | 0% | 2 studies (2/-) | 99.4 % | some concern | not evaluable | moderate | non important | - |
AE (grade 3-4) | 0.59 [0.26, 1.35] | | < 1 | | 88% | 2 studies (2/-) | 89.6 % | some concern | not evaluable | moderate | non important | - |
AE leading to death (grade 5) | 0.87 [0.42, 1.78] | | < 1 | | 0% | 2 studies (2/-) | 65.3 % | some concern | not evaluable | moderate | non important | - |
AE leading to treatment discontinuation (any grade) | 0.50 [0.23, 1.07] | | < 1 | | 67% | 2 studies (2/-) | 96.3 % | some concern | not evaluable | moderate | non important | - |
SAE (any grade) | 1.07 [0.80, 1.44] | | < 1 | | 0% | 2 studies (2/-) | 31.3 % | some concern | not evaluable | moderate | non important | - |
STRAE (any grade) | 0.84 [0.47, 1.51] | | < 1 | | 85% | 5 studies (5/-) | 71.5 % | some concern | serious | moderate | non important | - |
STRAE (grade 3-4) | 1.18 [0.66, 2.12] | | < 1 | | 77% | 3 studies (3/-) | 28.5 % | some concern | not evaluable | moderate | non important | - |
TRAE (any grade) | 0.28 [0.18, 0.44] | | < 1 | | 84% | 6 studies (6/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
TRAE (grade 3-4) | 0.33 [0.19, 0.57] | | < 1 | | 92% | 6 studies (6/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
TRAE leading to death (grade 5) | 0.84 [0.46, 1.53] | | < 1 | | 0% | 5 studies (5/-) | 71.8 % | some concern | not evaluable | moderate | non important | - |
TRAE leading to discontinuation (any grade) | 0.95 [0.49, 1.84] | | < 1 | | 86% | 5 studies (5/-) | 56.4 % | some concern | not evaluable | moderate | non important | - |
TRAE leading to discontinuation (grade 3-4) | 1.58 [0.73, 3.42] | | < 1 | | 82% | 4 studies (4/-) | 12.1 % | some concern | not evaluable | moderate | non important | - |
TRAE (grade 3-4) endpoints 00 |
Adrenal insufficiency TRAE (grade 3-4) | 3.88 [0.17, 86.15] | | < 1 | | 0% | 1 study (1/-) | 19.9 % | NA | not evaluable | | non important | - |
Alopecia TRAE (grade 3-4) | 0.18 [0.01, 2.28] | | < 1 | | 14% | 2 studies (2/-) | 90.5 % | some concern | not evaluable | moderate | non important | - |
Anaemia TRAE (grade 3-4) | 0.06 [0.03, 0.12] | | < 1 | | 18% | 4 studies (4/-) | 100.0 % | 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) | 0.47 [0.14, 1.63] | | < 1 | | 41% | 3 studies (3/-) | 88.3 % | some concern | not evaluable | moderate | non important | - |
Blood creatinine increased TRAE (grade 3-4) | 0.98 [0.09, 10.85] | | < 1 | | 0% | 2 studies (2/-) | 50.7 % | some concern | not evaluable | moderate | non important | - |
Colitis TRAE (grade 3-4) | 3.85 [0.82, 18.18] | | < 1 | | 0% | 3 studies (3/-) | 4.5 % | some concern | not evaluable | moderate | non important | - |
Constipation TRAE (grade 3-4) | 0.98 [0.14, 6.96] | | < 1 | | 0% | 4 studies (4/-) | 50.8 % | some concern | not evaluable | moderate | non important | - |
Decreased appetite TRAE (grade 3-4) | 0.53 [0.24, 1.15] | | < 1 | | 0% | 4 studies (4/-) | 94.7 % | some concern | not evaluable | moderate | non important | - |
Diabetes TRAE (grade 3-4) | 1.95 [0.07, 58.69] | | < 1 | | 0% | 1 study (1/-) | 35.2 % | NA | not evaluable | | non important | - |
Diarrhoea TRAE (grade 3-4) | 1.96 [0.76, 5.07] | | < 1 | | 23% | 4 studies (4/-) | 8.3 % | some concern | not evaluable | moderate | non important | - |
Dysgeusia TRAE (grade 3-4) | 0.98 [0.06, 15.72] | | < 1 | | 0% | 2 studies (2/-) | 50.6 % | some concern | not evaluable | moderate | non important | - |
Fatigue TRAE (grade 3-4) | 0.50 [0.17, 1.44] | | < 1 | | 59% | 4 studies (4/-) | 90.1 % | some concern | not evaluable | moderate | non important | - |
Gastrointestinal disorders TRAE (grade 3-4) | 1.19 [0.36, 3.94] | | < 1 | | 0% | 1 study (1/-) | 39.0 % | NA | not evaluable | | non important | - |
Hepatitis TRAE (grade 3-4) | 12.17 [2.30, 64.46] | | < 1 | | 0% | 2 studies (2/-) | 0.2 % | some concern | not evaluable | moderate | non important | - |
Hyperthyroidism TRAE (grade 3-4) | 1.26 [0.15, 10.81] | | < 1 | | 0% | 3 studies (3/-) | 41.7 % | some concern | not evaluable | moderate | non important | - |
Hypophysitis TRAE (grade 3-4) | 3.62 [0.38, 34.25] | | < 1 | | 0% | 2 studies (2/-) | 13.3 % | some concern | not evaluable | moderate | non important | - |
Hypothyroidism TRAE (grade 3-4) | 1.19 [0.18, 7.84] | | < 1 | | 0% | 4 studies (4/-) | 42.8 % | some concern | not evaluable | moderate | non important | - |
Increase AST TRAE (grade 3-4) | 1.94 [0.35, 10.63] | | < 1 | | 0% | 1 study (1/-) | 22.3 % | NA | not evaluable | | non important | - |
Increased ALT TRAE (grade 3-4) | 2.20 [0.89, 5.42] | | < 1 | | 0% | 2 studies (2/-) | 4.4 % | some concern | not evaluable | moderate | non important | - |
Infusion-related reactions TRAE (grade 3-4) | 0.31 [0.06, 1.66] | | < 1 | | 0% | 3 studies (3/-) | 91.4 % | some concern | not evaluable | moderate | non important | - |
Leucopenia TRAE (grade 3-4) | 0.05 [0.01, 0.38] | | < 1 | | 0% | 2 studies (2/-) | 99.8 % | some concern | not evaluable | moderate | non important | - |
Maculopapular rash TRAE (grade 3-4) | 1.97 [0.07, 59.09] | | < 1 | | 0% | 1 study (1/-) | 35.0 % | NA | not evaluable | | non important | - |
Mucosal inflammation TRAE (grade 3-4) | 0.98 [0.02, 49.83] | | < 1 | | 0% | 1 study (1/-) | 50.3 % | NA | not evaluable | | 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) | 0.97 [0.02, 49.41] | | < 1 | | 0% | 1 study (1/-) | 50.5 % | NA | not evaluable | | non important | - |
Nausea TRAE (grade 3-4) | 0.19 [0.07, 0.57] | | < 1 | | 0% | 4 studies (4/-) | 99.8 % | some concern | not evaluable | moderate | non important | - |
Nephritis TRAE (grade 3-4) | 1.94 [0.18, 21.52] | | < 1 | | 0% | 2 studies (2/-) | 29.5 % | some concern | not evaluable | moderate | non important | - |
Neutropenia TRAE (grade 3-4) | 0.02 [0.01, 0.06] | | < 1 | | 0% | 4 studies (4/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
Pancreatitis TRAE (grade 3-4) | 1.44 [0.11, 18.87] | | < 1 | | 0% | 2 studies (2/-) | 39.0 % | some concern | not evaluable | moderate | non important | - |
Peripheral neuropathy TRAE (grade 3-4) | 0.22 [0.02, 2.27] | | < 1 | | 0% | 2 studies (2/-) | 89.7 % | some concern | not evaluable | moderate | non important | - |
Peripheral oedema TRAE (grade 3-4) | 0.98 [0.02, 49.83] | | < 1 | | 0% | 1 study (1/-) | 50.3 % | 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 | - |
Pneumonitis TRAE (grade 3-4) | 8.21 [2.15, 31.32] | | < 1 | | 0% | 3 studies (3/-) | 0.1 % | some concern | not evaluable | moderate | non important | - |
Pruritus TRAE (grade 3-4) | 2.13 [0.34, 13.46] | | < 1 | | 0% | 3 studies (3/-) | 21.1 % | some concern | not evaluable | moderate | non important | - |
Pyrexia TRAE (grade 3-4) | 0.66 [0.05, 8.61] | | < 1 | | 0% | 2 studies (2/-) | 62.4 % | some concern | not evaluable | moderate | non important | - |
Rash TRAE (grade 3-4) | 2.93 [0.90, 9.56] | | < 1 | | 0% | 4 studies (4/-) | 3.7 % | some concern | not evaluable | moderate | non important | - |
Renal and urinary disorders TRAE (grade 3-4) | 1.97 [0.07, 59.09] | | < 1 | | 0% | 1 study (1/-) | 35.0 % | NA | not evaluable | | non important | - |
Respiratory, thoracic and mediastinal disorders TRAE (grade 3-4) | 12.07 [0.67, 217.19] | | < 1 | | 0% | 1 study (1/-) | 4.7 % | NA | not evaluable | | non important | - |
Severe skin reaction TRAE (grade 3-4) | 11.23 [2.11, 59.83] | | < 1 | | 0% | 2 studies (2/-) | 0.2 % | some concern | not evaluable | moderate | non important | - |
Skin and subcutaneous tissue disorders TRAE (grade 3-4) | 5.00 [0.58, 43.09] | | < 1 | | 0% | 1 study (1/-) | 7.3 % | NA | not evaluable | | non important | - |
Stomatitis TRAE (grade 3-4) | 0.44 [0.06, 3.17] | | < 1 | | 0% | 3 studies (3/-) | 79.2 % | some concern | not evaluable | moderate | non important | - |
Thrombocytopenia TRAE (grade 3-4) | 0.06 [0.02, 0.22] | | < 1 | | 0% | 3 studies (3/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
Thyroiditis TRAE (grade 3-4) | 0.97 [0.06, 15.56] | | < 1 | | 0% | 2 studies (2/-) | 50.8 % | some concern | not evaluable | moderate | non important | - |
Vomiting TRAE (grade 3-4) | 0.19 [0.05, 0.70] | | < 1 | | 0% | 4 studies (4/-) | 99.4 % | some concern | not evaluable | moderate | non important | - |
AE (grade 3-4) endpoints 00 |
Anaemia AE (grade 3-4) | 0.30 [0.02, 4.07] | | < 1 | | 93% | 2 studies (2/-) | 81.5 % | some concern | not evaluable | moderate | non important | - |
Arthralgia AE (grade 3-4) | 2.01 [0.36, 11.05] | | < 1 | | 0% | 1 study (1/-) | 21.3 % | NA | not evaluable | | non important | - |
Asthenia AE (grade 3-4) | 0.32 [0.08, 1.18] | | < 1 | | 0% | 2 studies (2/-) | 95.6 % | some concern | not evaluable | moderate | non important | - |
Back pain AE (grade 3-4) | 0.50 [0.04, 5.51] | | < 1 | | 0% | 1 study (1/-) | 71.4 % | NA | not evaluable | | non important | - |
Constipation AE (grade 3-4) | 1.19 [0.32, 4.49] | | < 1 | | 0% | 2 studies (2/-) | 39.8 % | some concern | not evaluable | moderate | non important | - |
Cough AE (grade 3-4) | 0.96 [0.09, 10.59] | | < 1 | | 0% | 2 studies (2/-) | 51.4 % | low | not evaluable | high | non important | - |
Decreased appetite AE (grade 3-4) | 4.76 [0.55, 41.15] | | < 1 | | 0% | 2 studies (2/-) | 7.9 % | low | not evaluable | high | non important | - |
Diarrhoea AE (grade 3-4) | 1.84 [0.04, 75.61] | | < 1 | | 75% | 2 studies (2/-) | 37.6 % | low | not evaluable | high | non important | - |
Dyspnoea AE (grade 3-4) | 1.00 [0.38, 2.66] | | < 1 | | 0% | 2 studies (2/-) | 49.8 % | low | not evaluable | high | non important | - |
Fatigue AE (grade 3-4) | 0.73 [0.15, 3.49] | | < 1 | | 58% | 2 studies (2/-) | 65.4 % | low | not evaluable | high | non important | - |
Febrile neutropenia AE (grade 3-4) | 0.05 [0.00, 0.86] | | < 1 | | 0% | 1 study (1/-) | 98.0 % | NA | not evaluable | | non important | - |
Hypertension AE (grade 3-4) | 0.61 [0.10, 3.68] | | < 1 | | 0% | 1 study (1/-) | 70.4 % | NA | not evaluable | | non important | - |
Hypothyroidism AE (grade 3-4) | 1.00 [0.06, 16.01] | | < 1 | | 0% | 1 study (1/-) | 50.1 % | NA | not evaluable | | non important | - |
Increase AST AE (grade 3-4) | 3.96 [1.30, 12.02] | | < 1 | | 0% | 3 studies (3/-) | 0.8 % | some concern | not evaluable | moderate | non important | - |
Increased ALT AE (grade 3-4) | 2.70 [0.95, 7.64] | | < 1 | | 0% | 2 studies (2/-) | 3.1 % | low | not evaluable | high | non important | - |
Leucopenia AE (grade 3-4) | 0.23 [0.03, 2.05] | | < 1 | | 0% | 1 study (1/-) | 90.5 % | NA | not evaluable | | non important | - |
Nausea AE (grade 3-4) | 0.69 [0.03, 13.97] | | < 1 | | 61% | 2 studies (2/-) | 59.4 % | some concern | not evaluable | moderate | non important | - |
Neutropenia AE (grade 3-4) | 0.03 [0.01, 0.14] | | < 1 | | 0% | 1 study (1/-) | 100.0 % | NA | not evaluable | | non important | - |
Pancytopenia (AE grade 3-4) | 0.46 [0.04, 5.08] | | < 1 | | 0% | 1 study (1/-) | 73.6 % | NA | not evaluable | | non important | - |
Pneumonia AE (grade 3-4) | 1.11 [0.61, 2.00] | | < 1 | | 14% | 2 studies (2/-) | 37.0 % | low | not evaluable | high | non important | - |
Pneumonitis AE (grade 3-4) | 2.21 [0.83, 5.91] | | < 1 | | 0% | 1 study (1/-) | 5.6 % | NA | not evaluable | | non important | - |
Pruritus AE (grade 3-4) | 0.50 [0.04, 5.51] | | < 1 | | 0% | 1 study (1/-) | 71.4 % | NA | not evaluable | | non important | - |
Pyrexia AE (grade 3-4) | 1.89 [0.15, 23.34] | | < 1 | | 19% | 2 studies (2/-) | 31.1 % | low | not evaluable | high | non important | - |
Rash AE (grade 3-4) | 16.38 [0.94, 286.59] | | < 1 | | 0% | 1 study (1/-) | 2.9 % | NA | not evaluable | | non important | - |
Sepsis AE (grade 3-4) | 0.46 [0.04, 5.08] | | < 1 | | 0% | 1 study (1/-) | 73.6 % | NA | not evaluable | | non important | - |
Thrombocytopenia AE (grade 3-4) | 0.05 [0.01, 0.34] | | < 1 | | 0% | 1 study (1/-) | 99.9 % | NA | not evaluable | | non important | - |
Vomiting AE (grade 3-4) | 1.44 [0.17, 12.08] | | < 1 | | 42% | 2 studies (2/-) | 37.0 % | low | not evaluable | high | non important | - |