| 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) | 0.72 [0.57, 0.92] | | < 1 | | 78% | 6 studies (6/-) | 99.6 % | low | not evaluable | high | 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) | 0.68 [0.49, 0.94] | | < 1 | | 93% | 6 studies (6/-) | 98.9 % | low | not evaluable | high | important | - |
| objective responses (ORR) | 1.90 [1.19, 3.04] | | > 1 | | 89% | 6 studies (6/-) | 99.6 % | low | not evaluable | high | 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) | 0.89 [0.65, 1.20] | | < 1 | | 0% | 3 studies (3/-) | 78.1 % | low | not evaluable | high | non important | - |
| Arthralgia AE (grade 3-4) | 2.02 [0.60, 6.74] | | < 1 | | 0% | 2 studies (2/-) | 12.7 % | low | not evaluable | high | non important | - |
| Asthenia AE (grade 3-4) | 0.84 [0.30, 2.41] | | < 1 | | 55% | 3 studies (3/-) | 62.4 % | 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) | 1.02 [0.33, 3.19] | | < 1 | | 0% | 3 studies (3/-) | 48.3 % | low | not evaluable | high | non important | - |
| Cough AE (grade 3-4) | 0.61 [0.14, 2.65] | | < 1 | | 0% | 3 studies (3/-) | 74.6 % | low | not evaluable | high | non important | - |
| Decreased appetite AE (grade 3-4) | 1.76 [0.66, 4.71] | | < 1 | | 0% | 3 studies (3/-) | 13.2 % | low | not evaluable | high | non important | - |
| Diarrhoea AE (grade 3-4) | 2.25 [1.07, 4.72] | | < 1 | | 18% | 3 studies (3/-) | 1.6 % | low | not evaluable | high | non important | - |
| Dyspnoea AE (grade 3-4) | 0.82 [0.44, 1.50] | | < 1 | | 0% | 3 studies (3/-) | 74.4 % | 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) | 1.38 [0.71, 2.67] | | < 1 | | 20% | 3 studies (3/-) | 17.1 % | 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) | 1.32 [0.15, 11.35] | | < 1 | | 0% | 2 studies (2/-) | 40.0 % | low | not evaluable | high | 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) | 1.01 [0.47, 2.16] | | < 1 | | 0% | 3 studies (3/-) | 49.1 % | 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) | 2.42 [1.05, 5.59] | | < 1 | | 0% | 2 studies (2/-) | 2.0 % | low | not evaluable | high | non important | - |
| Pyrexia AE (grade 3-4) | 1.56 [0.35, 6.84] | | < 1 | | 0% | 3 studies (3/-) | 28.0 % | low | not evaluable | high | non important | - |
| Rash AE (grade 3-4) | 3.20 [0.26, 39.60] | | < 1 | | 63% | 2 studies (2/-) | 18.4 % | low | not evaluable | high | 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) | 0.99 [0.22, 4.33] | | < 1 | | 55% | 3 studies (3/-) | 50.8 % | low | not evaluable | high | non important | - |
