| 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) | 0.74 [0.63, 0.87] | | < 1 | | 76% | 9 studies (9/-) | 100.0 % | some concern | not evaluable | moderate | crucial | - |
| deaths (OS) (extension) | 0.68 [0.56, 0.83] | | < 1 | | 68% | 4 studies (4/-) | 100.0 % | some concern | not evaluable | moderate | important | - |
| PFS (extension) | 0.66 [0.44, 0.98] | | < 1 | | 95% | 4 studies (4/-) | 98.0 % | some concern | not evaluable | moderate | important | - |
| progression or deaths (PFS) | 0.69 [0.54, 0.88] | | < 1 | | 91% | 9 studies (9/-) | 99.9 % | some concern | not evaluable | moderate | important | - |
| objective responses (ORR) | 1.57 [1.08, 2.28] | | > 1 | | 89% | 9 studies (9/-) | 99.1 % | some concern | not evaluable | moderate | non important | - |
| objective responses (ORR) (extension) | 1.87 [0.98, 3.57] | | > 1 | | 90% | 4 studies (4/-) | 97.1 % | some concern | not evaluable | moderate | non important | - |
safety endpoints 00 |
| AE (any grade) | 0.57 [0.26, 1.24] | | < 1 | | 77% | 6 studies (6/-) | 92.2 % | some concern | serious | moderate | non important | - |
| AE (grade 3-4) | 0.64 [0.38, 1.08] | | < 1 | | 92% | 6 studies (6/-) | 95.2 % | some concern | not evaluable | moderate | non important | - |
| AE leading to death (grade 5) | 0.95 [0.66, 1.35] | | < 1 | | 15% | 6 studies (6/-) | 61.5 % | low | not evaluable | high | non important | - |
| AE leading to treatment discontinuation (any grade) | 1.07 [0.57, 2.00] | | < 1 | | 87% | 6 studies (6/-) | 41.5 % | 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) | 1.07 [0.80, 1.44] | | < 1 | | 0% | 2 studies (2/-) | 31.3 % | some concern | not evaluable | moderate | non important | - |
| STRAE (any grade) | 0.72 [0.51, 1.03] | | < 1 | | 50% | 4 studies (4/-) | 96.5 % | some concern | not evaluable | moderate | non important | - |
| STRAE (grade 3-4) | 0.73 [0.49, 1.08] | | < 1 | | 39% | 3 studies (3/-) | 94.3 % | some concern | not evaluable | moderate | non important | - |
| TRAE (any grade) | 0.23 [0.19, 0.27] | | < 1 | | 0% | 5 studies (5/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
| TRAE (grade 3-4) | 0.27 [0.21, 0.33] | | < 1 | | 42% | 5 studies (5/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
| TRAE leading to death (grade 5) | 0.97 [0.56, 1.68] | | < 1 | | 0% | 5 studies (5/-) | 54.8 % | some concern | not evaluable | moderate | non important | - |
| TRAE leading to discontinuation (any grade) | 0.76 [0.59, 0.99] | | < 1 | | 0% | 4 studies (4/-) | 98.1 % | some concern | not evaluable | moderate | non important | - |
| TRAE leading to discontinuation (grade 3-4) | 1.12 [0.82, 1.53] | | < 1 | | 0% | 4 studies (4/-) | 23.4 % | some concern | not evaluable | moderate | non important | - |
TRAE (grade 3-4) endpoints 00 |
| Adrenal insufficiency TRAE (grade 3-4) | 1.39 [0.24, 8.16] | | < 1 | | 0% | 3 studies (3/-) | 35.7 % | some concern | not evaluable | moderate | non important | - |
| Alopecia TRAE (grade 3-4) | 0.27 [0.04, 1.98] | | < 1 | | 0% | 3 studies (3/-) | 90.0 % | some concern | not evaluable | moderate | non important | - |
| Anaemia TRAE (grade 3-4) | 0.04 [0.02, 0.09] | | < 1 | | 0% | 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) | 0.21 [0.07, 0.58] | | < 1 | | 0% | 3 studies (3/-) | 99.9 % | 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) | 2.96 [0.88, 9.97] | | < 1 | | 0% | 6 studies (6/-) | 4.0 % | some concern | serious | moderate | non important | - |
| Constipation TRAE (grade 3-4) | 0.78 [0.12, 5.15] | | < 1 | | 0% | 4 studies (4/-) | 60.0 % | some concern | not evaluable | moderate | non important | - |
| Decreased appetite TRAE (grade 3-4) | 0.37 [0.16, 0.87] | | < 1 | | 0% | 4 studies (4/-) | 98.9 % | some concern | not evaluable | moderate | non important | - |
| Diabetes TRAE (grade 3-4) | 1.26 [0.16, 9.77] | | < 1 | | 0% | 3 studies (3/-) | 41.4 % | some concern | not evaluable | moderate | non important | - |
| Diarrhoea TRAE (grade 3-4) | 1.29 [0.57, 2.94] | | < 1 | | 0% | 6 studies (6/-) | 26.9 % | 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) | 0.41 [0.22, 0.79] | | < 1 | | 0% | 4 studies (4/-) | 99.6 % | 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) | 6.10 [1.76, 21.13] | | < 1 | | 0% | 5 studies (5/-) | 0.2 % | some concern | serious | moderate | non important | - |
| Hyperthyroidism TRAE (grade 3-4) | 0.91 [0.21, 3.86] | | < 1 | | 0% | 7 studies (7/-) | 55.3 % | 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) | 1.41 [0.40, 5.02] | | < 1 | | 0% | 8 studies (8/-) | 29.9 % | some concern | serious | moderate | non important | - |
| Increase AST TRAE (grade 3-4) | 1.88 [0.47, 7.56] | | < 1 | | 0% | 3 studies (3/-) | 18.9 % | some concern | not evaluable | moderate | non important | - |
| Increased ALT TRAE (grade 3-4) | 2.03 [0.87, 4.76] | | < 1 | | 0% | 4 studies (4/-) | 5.2 % | some concern | not evaluable | moderate | non important | - |
| Infusion-related reactions TRAE (grade 3-4) | 0.39 [0.09, 1.76] | | < 1 | | 0% | 4 studies (4/-) | 89.0 % | 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) | 1.95 [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) | 1.94 [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) | 0.12 [0.03, 0.47] | | < 1 | | 0% | 4 studies (4/-) | 99.9 % | some concern | not evaluable | moderate | non important | - |
| Nephritis TRAE (grade 3-4) | 2.16 [0.46, 10.05] | | < 1 | | 0% | 5 studies (5/-) | 16.4 % | some concern | serious | 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) | 1.65 [0.23, 11.94] | | < 1 | | 0% | 3 studies (3/-) | 31.1 % | some concern | not evaluable | moderate | non important | - |
| Peripheral neuropathy TRAE (grade 3-4) | 0.44 [0.06, 3.02] | | < 1 | | 0% | 3 studies (3/-) | 79.7 % | 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) | 2.69 [1.09, 6.62] | | < 1 | | 20% | 7 studies (7/-) | 1.6 % | some concern | not evaluable | moderate | non important | - |
| Pruritus TRAE (grade 3-4) | 1.10 [0.19, 6.43] | | < 1 | | 0% | 4 studies (4/-) | 45.8 % | 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) | 1.46 [0.55, 3.91] | | < 1 | | 4% | 6 studies (6/-) | 22.5 % | 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) | 3.88 [0.61, 24.61] | | < 1 | | 62% | 3 studies (3/-) | 7.6 % | 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) | 0.05 [0.02, 0.17] | | < 1 | | 0% | 4 studies (4/-) | 100.0 % | 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) | 0.20 [0.05, 0.87] | | < 1 | | 0% | 4 studies (4/-) | 98.4 % | 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 | - |
| 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 | - |
| Leucopenia AE (grade 3-4) | 0.15 [0.03, 0.68] | | < 1 | | 0% | 2 studies (2/-) | 99.3 % | some concern | not evaluable | moderate | 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 | - |
| myocarditis AE (grade 3-4) | 0.96 [0.02, 48.69] | | < 1 | | 0% | 1 study (1/-) | 50.7 % | NA | not evaluable | | non important | - |
| Nausea AE (grade 3-4) | 0.50 [0.21, 1.16] | | < 1 | | 22% | 5 studies (5/-) | 94.8 % | low | serious | high | non important | - |
| Neutropenia AE (grade 3-4) | 0.20 [0.06, 0.71] | | < 1 | | 93% | 5 studies (5/-) | 99.4 % | some concern | serious | moderate | non important | - |
| Pancytopenia (AE grade 3-4) | 0.47 [0.07, 3.32] | | < 1 | | 0% | 2 studies (2/-) | 77.6 % | some concern | not evaluable | moderate | non important | - |
