| 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 | | 65% | 13 studies (13/-) | 100.0 % | some concern | low | moderate | crucial | - |
| deaths (OS) (extension) | 0.69 [0.58, 0.81] | | < 1 | | 57% | 5 studies (5/-) | 100.0 % | some concern | not evaluable | moderate | important | - |
| PFS (extension) | 0.64 [0.44, 0.91] | | < 1 | | 94% | 5 studies (5/-) | 99.3 % | some concern | not evaluable | moderate | important | - |
| progression or deaths (PFS) | 0.68 [0.58, 0.81] | | < 1 | | 87% | 13 studies (13/-) | 100.0 % | some concern | low | moderate | important | - |
| DOR | 2.27 [1.44, 3.57] | | < 1 | | 0% | 2 studies (2/-) | 0.0 % | some concern | not evaluable | moderate | non important | - |
| objective responses (ORR) | 1.66 [1.24, 2.22] | | > 1 | | 86% | 12 studies (12/-) | 100.0 % | some concern | low | moderate | non important | - |
| objective responses (ORR) (extension) | 2.00 [1.13, 3.54] | | > 1 | | 88% | 5 studies (5/-) | 99.2 % | some concern | not evaluable | moderate | non important | - |
safety endpoints 00 |
| AE (any grade) | 0.80 [0.34, 1.88] | | < 1 | | 82% | 7 studies (7/-) | 69.7 % | some concern | serious | moderate | non important | - |
| AE (grade 3-4) | 0.72 [0.44, 1.16] | | < 1 | | 92% | 7 studies (7/-) | 91.2 % | some concern | not evaluable | moderate | non important | - |
| AE leading to death (grade 5) | 1.09 [0.70, 1.70] | | < 1 | | 55% | 7 studies (7/-) | 34.5 % | some concern | serious | moderate | non important | - |
| AE leading to treatment discontinuation (any grade) | 1.19 [0.69, 2.04] | | < 1 | | 87% | 7 studies (7/-) | 26.4 % | some concern | not evaluable | moderate | non important | - |
| AE leading to treatment discontinuation (grade 3-4) | 1.43 [0.89, 2.29] | | < 1 | | 61% | 4 studies (4/-) | 7.2 % | low | not evaluable | high | non important | - |
| SAE (any grade) | 1.42 [0.82, 2.44] | | < 1 | | 84% | 3 studies (3/-) | 10.4 % | some concern | not evaluable | moderate | non important | - |
| STRAE (any grade) | 1.15 [0.70, 1.87] | | < 1 | | 83% | 7 studies (7/-) | 29.1 % | some concern | not evaluable | moderate | non important | - |
| STRAE (grade 3-4) | 1.16 [0.62, 2.15] | | < 1 | | 79% | 5 studies (5/-) | 32.1 % | some concern | not evaluable | moderate | non important | - |
| TRAE (any grade) | 0.48 [0.25, 0.94] | | < 1 | | 93% | 8 studies (8/-) | 98.4 % | some concern | serious | moderate | non important | - |
| TRAE (grade 3-4) | 0.55 [0.27, 1.10] | | < 1 | | 96% | 8 studies (8/-) | 95.5 % | some concern | not evaluable | moderate | non important | - |
| TRAE leading to death (grade 5) | 1.05 [0.64, 1.73] | | < 1 | | 0% | 8 studies (8/-) | 42.0 % | some concern | not evaluable | moderate | non important | - |
| TRAE leading to discontinuation (any grade) | 0.78 [0.62, 0.98] | | < 1 | | 0% | 6 studies (6/-) | 98.2 % | some concern | not evaluable | moderate | non important | - |
| TRAE leading to discontinuation (grade 3-4) | 1.09 [0.82, 1.45] | | < 1 | | 0% | 6 studies (6/-) | 26.9 % | 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) | 1.51 [0.31, 7.22] | | < 1 | | 0% | 4 studies (4/-) | 30.5 % | some concern | not evaluable | moderate | non important | - |
| Alopecia TRAE (grade 3-4) | 0.42 [0.08, 2.15] | | < 1 | | 0% | 5 studies (5/-) | 84.9 % | some concern | serious | moderate | non important | - |
| Anaemia TRAE (grade 3-4) | 0.18 [0.06, 0.60] | | < 1 | | 92% | 7 studies (7/-) | 99.7 % | some concern | serious | moderate | non important | - |
| Arthralgia TRAE (grade 3-4) | 0.98 [0.06, 15.75] | | < 1 | | 0% | 2 studies (2/-) | 50.5 % | some concern | not evaluable | moderate | non important | - |
| Asthenia TRAE (grade 3-4) | 0.42 [0.20, 0.88] | | < 1 | | 7% | 5 studies (5/-) | 98.9 % | some concern | not evaluable | moderate | non important | - |
| Blood creatinine increased TRAE (grade 3-4) | 1.00 [0.13, 7.77] | | < 1 | | 0% | 3 studies (3/-) | 50.1 % | some concern | not evaluable | moderate | non important | - |
| Colitis TRAE (grade 3-4) | 3.43 [1.11, 10.53] | | < 1 | | 0% | 7 studies (7/-) | 1.6 % | some concern | not evaluable | moderate | non important | - |
| Constipation TRAE (grade 3-4) | 0.61 [0.16, 2.39] | | < 1 | | 0% | 7 studies (7/-) | 76.0 % | some concern | serious | moderate | non important | - |
| Decreased appetite TRAE (grade 3-4) | 0.73 [0.30, 1.78] | | < 1 | | 39% | 7 studies (7/-) | 75.4 % | some concern | not evaluable | moderate | non important | - |
| Diabetes TRAE (grade 3-4) | 2.07 [0.38, 11.27] | | < 1 | | 0% | 4 studies (4/-) | 20.0 % | some concern | not evaluable | moderate | non important | - |
| Diarrhoea TRAE (grade 3-4) | 1.29 [0.71, 2.32] | | < 1 | | 0% | 9 studies (9/-) | 20.1 % | 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) | 1.00 [0.10, 9.69] | | < 1 | | 0% | 3 studies (3/-) | 49.9 % | some concern | not evaluable | moderate | non important | - |
| Fatigue TRAE (grade 3-4) | 0.79 [0.37, 1.70] | | < 1 | | 56% | 7 studies (7/-) | 72.4 % | some concern | not evaluable | moderate | non important | - |
| Febrile neutropenia TRAE (grade 3-4) | 2.62 [1.11, 6.19] | | < 1 | | 0% | 2 studies (2/-) | 1.4 % | 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 | - |
| Guillain-Barré syndrome TRAE (grade 3-4) | 1.00 [0.02, 50.55] | | < 1 | | 0% | 1 study (1/-) | 50.0 % | NA | not evaluable | | non important | - |
| Hepatitis TRAE (grade 3-4) | 4.51 [1.45, 14.02] | | < 1 | | 0% | 6 studies (6/-) | 0.5 % | some concern | not evaluable | moderate | non important | - |
| Hyperthyroidism TRAE (grade 3-4) | 1.03 [0.29, 3.63] | | < 1 | | 0% | 9 studies (9/-) | 48.4 % | some concern | serious | moderate | non important | - |
| Hypophysitis TRAE (grade 3-4) | 1.87 [0.33, 10.75] | | < 1 | | 0% | 4 studies (4/-) | 24.1 % | some concern | not evaluable | moderate | non important | - |
| Hypothyroidism TRAE (grade 3-4) | 1.58 [0.51, 4.87] | | < 1 | | 0% | 10 studies (10/-) | 21.4 % | some concern | critical | moderate | non important | - |
| Increase AST TRAE (grade 3-4) | 1.67 [0.48, 5.82] | | < 1 | | 0% | 4 studies (4/-) | 21.0 % | some concern | not evaluable | moderate | non important | - |
| Increased ALT TRAE (grade 3-4) | 1.92 [0.85, 4.34] | | < 1 | | 0% | 5 studies (5/-) | 5.8 % | 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) | 0.55 [0.15, 2.03] | | < 1 | | 0% | 6 studies (6/-) | 81.4 % | some concern | serious | moderate | non important | - |
| Leucopenia TRAE (grade 3-4) | 0.35 [0.04, 2.78] | | < 1 | | 69% | 4 studies (4/-) | 83.9 % | some concern | not evaluable | moderate | non important | - |
| Maculopapular rash TRAE (grade 3-4) | 1.95 [0.18, 21.58] | | < 1 | | 0% | 2 studies (2/-) | 29.4 % | some concern | not evaluable | moderate | 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) | 1.46 [0.11, 19.02] | | < 1 | | 0% | 2 studies (2/-) | 38.8 % | some concern | not evaluable | moderate | 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) | 0.79 [0.08, 7.57] | | < 1 | | 0% | 3 studies (3/-) | 58.2 % | some concern | not evaluable | moderate | non important | - |
| Nausea TRAE (grade 3-4) | 0.48 [0.15, 1.56] | | < 1 | | 48% | 7 studies (7/-) | 88.9 % | some concern | not evaluable | moderate | non important | - |
| Nephritis TRAE (grade 3-4) | 1.95 [0.47, 8.16] | | < 1 | | 0% | 6 studies (6/-) | 18.1 % | some concern | serious | moderate | non important | - |
| Neutropenia TRAE (grade 3-4) | 0.18 [0.05, 0.60] | | < 1 | | 86% | 7 studies (7/-) | 99.7 % | some concern | serious | moderate | non important | - |
| Pancreatitis TRAE (grade 3-4) | 1.73 [0.31, 9.58] | | < 1 | | 0% | 4 studies (4/-) | 26.5 % | 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) | 0.98 [0.25, 3.89] | | < 1 | | 9% | 4 studies (4/-) | 51.1 % | some concern | not evaluable | moderate | non important | - |
| Peripheral oedema TRAE (grade 3-4) | 1.02 [0.06, 16.38] | | < 1 | | 0% | 2 studies (2/-) | 49.5 % | some concern | not evaluable | moderate | non important | - |
| Peripheral sensory neuropathy TRAE (grade 3-4) | 0.64 [0.01, 29.61] | | < 1 | | 78% | 2 studies (2/-) | 58.9 % | some concern | not evaluable | moderate | 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) | 2.23 [1.15, 4.32] | | < 1 | | 0% | 9 studies (9/-) | 0.9 % | some concern | not evaluable | moderate | non important | - |
| Pruritus TRAE (grade 3-4) | 1.09 [0.24, 4.83] | | < 1 | | 0% | 6 studies (6/-) | 45.6 % | 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) | 1.58 [0.69, 3.65] | | < 1 | | 0% | 9 studies (9/-) | 14.1 % | 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 | - |
| 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) | 2.45 [0.73, 8.21] | | < 1 | | 30% | 5 studies (5/-) | 7.3 % | 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) | 0.46 [0.08, 2.53] | | < 1 | | 0% | 4 studies (4/-) | 81.4 % | some concern | not evaluable | moderate | non important | - |
| Thrombocytopenia TRAE (grade 3-4) | 0.17 [0.04, 0.83] | | < 1 | | 78% | 6 studies (6/-) | 98.5 % | some concern | serious | 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) | 0.69 [0.23, 2.02] | | < 1 | | 22% | 7 studies (7/-) | 75.2 % | some concern | not evaluable | moderate | non important | - |
AE (grade 3-4) endpoints 00 |
| hepatitis (Autoimmune) AE (grade 3-4) | 5.05 [0.55, 46.09] | | < 1 | | 0% | 2 studies (2/-) | 7.7 % | low | not evaluable | high | non important | - |
| Acute kidney injury AE (grade 3-4) | 0.24 [0.01, 5.34] | | < 1 | | 0% | 1 study (1/-) | 81.4 % | NA | not evaluable | | non important | - |
| Alopecia AE (grade 3-4) | 0.37 [0.07, 1.93] | | < 1 | | 0% | 3 studies (3/-) | 88.1 % | low | not evaluable | high | non important | - |
| Anaemia AE (grade 3-4) | 0.23 [0.08, 0.66] | | < 1 | | 92% | 5 studies (5/-) | 99.7 % | some concern | serious | moderate | non important | - |
| Arthralgia AE (grade 3-4) | 1.52 [0.33, 6.97] | | < 1 | | 0% | 2 studies (2/-) | 29.6 % | low | not evaluable | high | non important | - |
| Asthenia AE (grade 3-4) | 0.94 [0.55, 1.61] | | < 1 | | 11% | 5 studies (5/-) | 59.2 % | low | not evaluable | high | non important | - |
| Back pain AE (grade 3-4) | 0.36 [0.05, 2.37] | | < 1 | | 0% | 2 studies (2/-) | 85.5 % | some concern | not evaluable | moderate | non important | - |
| Blood creatinine increased AE (grade 3-4) | 0.48 [0.02, 14.38] | | < 1 | | 0% | 1 study (1/-) | 66.1 % | NA | not evaluable | | 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) | 1.12 [0.41, 3.00] | | < 1 | | 0% | 5 studies (5/-) | 41.5 % | low | not evaluable | high | non important | - |
| Cough AE (grade 3-4) | 0.89 [0.23, 3.46] | | < 1 | | 0% | 4 studies (4/-) | 56.4 % | low | not evaluable | high | non important | - |
| Decreased appetite AE (grade 3-4) | 1.52 [0.71, 3.21] | | < 1 | | 0% | 5 studies (5/-) | 14.0 % | low | not evaluable | high | non important | - |
| Diarrhoea AE (grade 3-4) | 0.83 [0.33, 2.14] | | < 1 | | 50% | 5 studies (5/-) | 64.7 % | low | serious | high | non important | - |
| Dyspnoea AE (grade 3-4) | 1.10 [0.62, 1.96] | | < 1 | | 0% | 5 studies (5/-) | 37.4 % | 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) | 1.02 [0.57, 1.84] | | < 1 | | 28% | 5 studies (5/-) | 47.1 % | low | not evaluable | high | non important | - |
| Febrile neutropenia AE (grade 3-4) | 0.05 [0.01, 0.41] | | < 1 | | 0% | 2 studies (2/-) | 99.8 % | some concern | not evaluable | moderate | non important | - |
| Hypertension AE (grade 3-4) | 0.48 [0.10, 2.29] | | < 1 | | 0% | 2 studies (2/-) | 82.0 % | some concern | not evaluable | moderate | 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 | - |
| Increase AST AE (grade 3-4) | 5.45 [1.59, 18.72] | | < 1 | | 0% | 3 studies (3/-) | 0.4 % | some concern | not evaluable | moderate | non important | - |
| Increased ALT AE (grade 3-4) | 5.03 [0.87, 28.91] | | < 1 | | 0% | 2 studies (2/-) | 3.6 % | some concern | not evaluable | moderate | non important | - |
| Increased Lipase Level AE (grade 3-4) | 1.93 [0.06, 57.70] | | < 1 | | 0% | 1 study (1/-) | 35.4 % | NA | not evaluable | | non important | - |
