| 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) | 0.79 [0.73, 0.87] | | < 1 | | 61% | 17 studies (17/-) | 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) | 0.70 [0.61, 0.80] | | < 1 | | 87% | 18 studies (18/-) | 100.0 % | some concern | critical | 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) | 1.60 [1.29, 1.98] | | > 1 | | 84% | 17 studies (17/-) | 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 [0.38, 1.68] | | < 1 | | 78% | 9 studies (9/-) | 72.3 % | some concern | serious | moderate | non important | - |
| AE (grade 3-4) | 0.83 [0.56, 1.25] | | < 1 | | 92% | 9 studies (9/-) | 81.1 % | some concern | not evaluable | moderate | non important | - |
| AE leading to death (grade 5) | 1.09 [0.79, 1.51] | | < 1 | | 41% | 9 studies (9/-) | 29.6 % | some concern | serious | moderate | non important | - |
| AE leading to treatment discontinuation (any grade) | 1.24 [0.86, 1.80] | | < 1 | | 83% | 9 studies (9/-) | 12.7 % | 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) | 1.48 [1.12, 1.95] | | < 1 | | 69% | 5 studies (5/-) | 0.3 % | some concern | not evaluable | moderate | non important | - |
| STRAE (any grade) | 1.26 [0.86, 1.84] | | < 1 | | 81% | 9 studies (9/-) | 11.7 % | 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) | 0.59 [0.31, 1.10] | | < 1 | | 93% | 10 studies (10/-) | 95.1 % | some concern | critical | moderate | non important | - |
| TRAE (grade 3-4) | 0.68 [0.37, 1.26] | | < 1 | | 96% | 10 studies (10/-) | 88.9 % | some concern | low | moderate | non important | - |
| TRAE leading to death (grade 5) | 1.15 [0.75, 1.76] | | < 1 | | 0% | 10 studies (10/-) | 25.7 % | some concern | low | 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) | 1.36 [0.35, 5.34] | | < 1 | | 0% | 5 studies (5/-) | 32.8 % | some concern | not evaluable | moderate | non important | - |
| Alopecia TRAE (grade 3-4) | 0.48 [0.12, 1.95] | | < 1 | | 0% | 7 studies (7/-) | 84.6 % | some concern | serious | moderate | non important | - |
| Anaemia TRAE (grade 3-4) | 0.35 [0.16, 0.76] | | < 1 | | 91% | 9 studies (9/-) | 99.6 % | some concern | serious | moderate | non important | - |
| Arthralgia TRAE (grade 3-4) | 0.80 [0.21, 2.99] | | < 1 | | 0% | 3 studies (3/-) | 63.1 % | some concern | not evaluable | moderate | non important | - |
| Asthenia TRAE (grade 3-4) | 0.52 [0.29, 0.95] | | < 1 | | 15% | 7 studies (7/-) | 98.3 % | 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) | 3.11 [1.23, 7.86] | | < 1 | | 0% | 8 studies (8/-) | 0.8 % | some concern | not evaluable | moderate | non important | - |
| Constipation TRAE (grade 3-4) | 0.68 [0.20, 2.27] | | < 1 | | 0% | 9 studies (9/-) | 73.5 % | some concern | serious | moderate | non important | - |
| Decreased appetite TRAE (grade 3-4) | 0.95 [0.46, 1.96] | | < 1 | | 41% | 9 studies (9/-) | 55.4 % | some concern | not evaluable | moderate | non important | - |
| Diabetes TRAE (grade 3-4) | 1.85 [0.39, 8.75] | | < 1 | | 0% | 5 studies (5/-) | 21.9 % | some concern | serious | moderate | non important | - |
| Diarrhoea TRAE (grade 3-4) | 1.35 [0.87, 2.09] | | < 1 | | 0% | 11 studies (11/-) | 9.3 % | some concern | low | 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) | 0.84 [0.12, 5.97] | | < 1 | | 0% | 4 studies (4/-) | 57.0 % | some concern | not evaluable | moderate | non important | - |
| Epistaxis TRAE (grade 3-4) | 8.09 [0.43, 153.59] | | < 1 | | 0% | 1 study (1/-) | 8.4 % | NA | not evaluable | | non important | - |
| Fatigue TRAE (grade 3-4) | 0.91 [0.54, 1.51] | | < 1 | | 45% | 9 studies (9/-) | 64.6 % | some concern | not evaluable | moderate | non important | - |
| Febrile neutropenia TRAE (grade 3-4) | 1.75 [1.10, 2.78] | | < 1 | | 0% | 3 studies (3/-) | 0.9 % | 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) | 4.87 [1.69, 14.02] | | < 1 | | 0% | 7 studies (7/-) | 0.2 % | some concern | not evaluable | moderate | non important | - |
| Hypertension TRAE (grade 3-4) | 1.00 [0.57, 1.78] | | < 1 | | 0% | 1 study (1/-) | 49.6 % | NA | not evaluable | | non important | - |
| Hyperthyroidism TRAE (grade 3-4) | 1.11 [0.34, 3.64] | | < 1 | | 0% | 10 studies (10/-) | 42.9 % | some concern | critical | moderate | non important | - |
| Hypophysitis TRAE (grade 3-4) | 1.90 [0.40, 8.99] | | < 1 | | 0% | 5 studies (5/-) | 21.0 % | some concern | serious | moderate | non important | - |
| Hypothyroidism TRAE (grade 3-4) | 1.62 [0.55, 4.71] | | < 1 | | 0% | 11 studies (11/-) | 19.0 % | some concern | critical | moderate | non important | - |
| Increase AST TRAE (grade 3-4) | 2.07 [0.70, 6.13] | | < 1 | | 0% | 5 studies (5/-) | 9.4 % | some concern | not evaluable | moderate | non important | - |
| Increased ALT TRAE (grade 3-4) | 2.10 [0.98, 4.51] | | < 1 | | 0% | 6 studies (6/-) | 2.8 % | 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) | 0.65 [0.18, 2.35] | | < 1 | | 61% | 5 studies (5/-) | 74.1 % | 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) | 1.73 [0.30, 10.01] | | < 1 | | 0% | 3 studies (3/-) | 27.1 % | 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) | 1.05 [0.16, 6.91] | | < 1 | | 0% | 4 studies (4/-) | 48.0 % | some concern | not evaluable | moderate | non important | - |
| Nausea TRAE (grade 3-4) | 0.83 [0.37, 1.88] | | < 1 | | 48% | 9 studies (9/-) | 67.2 % | some concern | serious | moderate | non important | - |
| Nephritis TRAE (grade 3-4) | 1.96 [0.52, 7.32] | | < 1 | | 0% | 7 studies (7/-) | 16.0 % | some concern | serious | moderate | non important | - |
| Neutropenia TRAE (grade 3-4) | 0.48 [0.25, 0.92] | | < 1 | | 83% | 9 studies (9/-) | 98.7 % | some concern | serious | moderate | non important | - |
| Pancreatitis TRAE (grade 3-4) | 2.11 [0.47, 9.43] | | < 1 | | 0% | 5 studies (5/-) | 16.5 % | some concern | serious | 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 | - |
| Paraesthesia TRAE (grade 3-4) | 0.50 [0.02, 14.97] | | < 1 | | 0% | 1 study (1/-) | 65.3 % | NA | not evaluable | | non important | - |
| Peripheral neuropathy TRAE (grade 3-4) | 1.16 [0.56, 2.42] | | < 1 | | 0% | 5 studies (5/-) | 34.3 % | 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) | 2.33 [1.26, 4.30] | | < 1 | | 0% | 10 studies (10/-) | 0.3 % | some concern | low | 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) | 2.02 [0.97, 4.21] | | < 1 | | 0% | 10 studies (10/-) | 3.1 % | some concern | low | 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) | 2.06 [0.19, 22.93] | | < 1 | | 0% | 2 studies (2/-) | 27.9 % | some concern | not evaluable | moderate | 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) | 1.04 [0.27, 4.02] | | < 1 | | 0% | 5 studies (5/-) | 47.6 % | some concern | not evaluable | moderate | non important | - |
| Thrombocytopenia TRAE (grade 3-4) | 0.44 [0.19, 1.01] | | < 1 | | 74% | 8 studies (8/-) | 97.4 % | 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) | 1.00 [0.51, 1.94] | | < 1 | | 5% | 9 studies (9/-) | 50.4 % | some concern | not evaluable | moderate | non important | - |
AE (grade 3-4) endpoints 00 |
| hepatitis (Autoimmune) AE (grade 3-4) | 3.10 [0.49, 19.80] | | < 1 | | 0% | 3 studies (3/-) | 11.7 % | some concern | not evaluable | moderate | non important | - |
| Abdominal pain AE (grade 3-4) | 1.23 [0.24, 6.38] | | < 1 | | 0% | 1 study (1/-) | 40.4 % | NA | not evaluable | | 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 | - |
| Agranulocytosis (AE grade 3-4) | 0.24 [0.01, 7.31] | | < 1 | | 0% | 1 study (1/-) | 78.8 % | NA | not evaluable | | non important | - |
| Alopecia AE (grade 3-4) | 0.38 [0.08, 1.76] | | < 1 | | 0% | 4 studies (4/-) | 89.0 % | some concern | not evaluable | moderate | non important | - |
| Anaemia AE (grade 3-4) | 0.39 [0.17, 0.87] | | < 1 | | 92% | 7 studies (7/-) | 98.9 % | some concern | serious | moderate | non important | - |
| Arthralgia AE (grade 3-4) | 2.12 [0.74, 6.09] | | < 1 | | 0% | 4 studies (4/-) | 8.2 % | low | not evaluable | high | non important | - |
| Asthenia AE (grade 3-4) | 0.97 [0.60, 1.57] | | < 1 | | 13% | 7 studies (7/-) | 55.0 % | some concern | not evaluable | moderate | non important | - |
| Back pain AE (grade 3-4) | 0.87 [0.25, 3.00] | | < 1 | | 4% | 4 studies (4/-) | 58.8 % | some concern | not evaluable | moderate | non important | - |
| Blood creatinine increased AE (grade 3-4) | 1.04 [0.10, 10.25] | | < 1 | | 0% | 2 studies (2/-) | 48.8 % | some concern | not evaluable | moderate | non important | - |
| Colitis AE (grade 3-4) | 2.18 [0.61, 7.72] | | < 1 | | 0% | 2 studies (2/-) | 11.5 % | low | not evaluable | high | non important | - |
| Constipation AE (grade 3-4) | 1.24 [0.53, 2.89] | | < 1 | | 0% | 7 studies (7/-) | 31.0 % | low | not evaluable | high | non important | - |
| Cough AE (grade 3-4) | 1.00 [0.31, 3.18] | | < 1 | | 0% | 6 studies (6/-) | 50.1 % | low | not evaluable | high | non important | - |
| Decreased appetite AE (grade 3-4) | 1.40 [0.76, 2.56] | | < 1 | | 0% | 7 studies (7/-) | 13.8 % | some concern | serious | moderate | non important | - |
| Diabetes mellitus AE (grade 3-4) | 1.97 [0.09, 43.77] | | < 1 | | 0% | 1 study (1/-) | 33.7 % | NA | not evaluable | | non important | - |
| Diarrhoea AE (grade 3-4) | 1.07 [0.51, 2.26] | | < 1 | | 54% | 7 studies (7/-) | 42.5 % | some concern | not evaluable | moderate | non important | - |
| Dizziness AE (grade 3-4) | 0.49 [0.03, 7.86] | | < 1 | | 0% | 1 study (1/-) | 69.1 % | NA | not evaluable | | non important | - |
| Dry skin AE (grade 3-4) | 0.24 [0.01, 7.31] | | < 1 | | 0% | 1 study (1/-) | 78.8 % | NA | not evaluable | | non important | - |
| Dysgeusia AE (grade 3-4) | 0.49 [0.01, 24.77] | | < 1 | | 0% | 1 study (1/-) | 63.7 % | NA | not evaluable | | non important | - |
| Dyspnoea AE (grade 3-4) | 1.41 [0.77, 2.60] | | < 1 | | 28% | 7 studies (7/-) | 13.5 % | low | serious | high | non important | - |
| Epistaxis AE (grade 3-4) | 0.62 [0.06, 6.00] | | < 1 | | 0% | 2 studies (2/-) | 65.8 % | some concern | not evaluable | moderate | non important | - |
