| 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 [0.65, 0.93] | | < 1 | | 14% | 2 studies (2/-) | 99.7 % | low | not evaluable | high | crucial | - |
| deaths (OS) (extension) | 0.73 [0.64, 0.83] | | < 1 | | 0% | 1 study (1/-) | 100.0 % | NA | not evaluable | | important | - |
| MFS | 0.70 [0.58, 0.84] | | < 1 | | 36% | 3 studies (3/-) | 100.0 % | low | not evaluable | high | important | - |
| MFS (extension) | 0.76 [0.64, 0.90] | | < 1 | | 0% | 1 study (1/-) | 99.9 % | NA | not evaluable | | important | - |
| RFS (extension) | 0.67 [0.56, 0.80] | | < 1 | | 65% | 3 studies (3/-) | 100.0 % | low | not evaluable | high | important | - |
| RFS/DFS | 0.56 [0.44, 0.71] | | < 1 | | 67% | 6 studies (6/-) | 100.0 % | low | serious | high | important | - |
| DMFS | 0.60 [0.49, 0.73] | | < 1 | | 0% | 1 study (1/-) | 100.0 % | NA | not evaluable | | non important | - |
safety endpoints 00 |
| AE (any grade) | 1.78 [0.49, 6.49] | | < 1 | | 89% | 3 studies (3/-) | 19.3 % | low | not evaluable | high | non important | - |
| AE (grade 3-4) | 0.40 [0.08, 2.07] | | < 1 | | 99% | 3 studies (3/-) | 86.1 % | low | not evaluable | high | non important | - |
| AE leading to death (grade 5) | 0.96 [0.10, 9.29] | | < 1 | | 0% | 3 studies (3/-) | 51.5 % | low | not evaluable | high | non important | - |
| AE leading to treatment discontinuation (any grade) | 3.76 [0.18, 78.09] | | < 1 | | 97% | 4 studies (4/-) | 19.9 % | low | not evaluable | high | non important | - |
| AE leading to treatment discontinuation (grade 3-4) | 4.01 [0.15, 108.15] | | < 1 | | 97% | 4 studies (4/-) | 20.8 % | low | not evaluable | high | non important | - |
| SAE (any grade) | 2.78 [1.29, 5.99] | | < 1 | | 63% | 3 studies (3/-) | 0.5 % | low | not evaluable | high | non important | - |
| SAE (grade 3-4) | 4.20 [2.10, 8.40] | | < 1 | | 43% | 3 studies (3/-) | 0.0 % | low | not evaluable | high | non important | - |
| STRAE (any grade) | 9.58 [3.26, 28.15] | | < 1 | | 53% | 3 studies (3/-) | 0.0 % | low | not evaluable | high | non important | - |
| STRAE (grade 3-4) | 13.45 [2.19, 82.46] | | < 1 | | 54% | 3 studies (3/-) | 0.3 % | low | not evaluable | high | non important | - |
| TRAE (any grade) | 3.60 [0.93, 13.97] | | < 1 | | 97% | 6 studies (6/-) | 3.3 % | low | not evaluable | high | non important | - |
| TRAE (grade 3-4) | 5.65 [0.74, 42.94] | | < 1 | | 98% | 6 studies (6/-) | 4.8 % | low | serious | high | non important | - |
| TRAE leading to death (grade 5) | 1.43 [0.35, 5.87] | | < 1 | | 0% | 6 studies (6/-) | 31.0 % | low | not evaluable | high | non important | - |
| TRAE leading to discontinuation (any grade) | 6.67 [0.34, 129.36] | | < 1 | | 99% | 5 studies (5/-) | 10.7 % | low | not evaluable | high | non important | - |
| TRAE leading to discontinuation (grade 3-4) | 5.00 [0.14, 181.21] | | < 1 | | 97% | 4 studies (4/-) | 19.4 % | low | not evaluable | high | non important | - |
TRAE (grade 3-4) endpoints 00 |
| Abdominal pain TRAE (grade 3-4) | 0.78 [0.12, 5.16] | | < 1 | | 0% | 4 studies (4/-) | 60.2 % | low | not evaluable | high | non important | - |
| Acute kidney injury TRAE (grade 3-4) | 1.59 [0.20, 12.46] | | < 1 | | 0% | 3 studies (3/-) | 33.0 % | low | not evaluable | high | non important | - |
| Adrenal insufficiency TRAE (grade 3-4) | 0.90 [0.26, 3.05] | | < 1 | | 0% | 5 studies (5/-) | 56.8 % | low | serious | high | non important | - |
| Alopecia TRAE (grade 3-4) | 0.95 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
| Anaemia TRAE (grade 3-4) | 1.59 [0.20, 12.46] | | < 1 | | 0% | 3 studies (3/-) | 33.0 % | low | not evaluable | high | non important | - |
| Arthralgia TRAE (grade 3-4) | 1.13 [0.29, 4.32] | | < 1 | | 0% | 5 studies (5/-) | 43.1 % | low | not evaluable | high | non important | - |
| Asthenia TRAE (grade 3-4) | 0.25 [0.03, 2.24] | | < 1 | | 0% | 1 study (1/-) | 89.1 % | NA | not evaluable | | non important | - |
| Blood and lymphatic system disorders TRAE (grade 3-4) | 2.58 [0.36, 18.33] | | < 1 | | 0% | 3 studies (3/-) | 17.3 % | low | not evaluable | high | non important | - |
| Blood creatinine increased TRAE (grade 3-4) | 0.92 [0.06, 14.87] | | < 1 | | 0% | 2 studies (2/-) | 52.4 % | low | not evaluable | high | non important | - |
| Chills TRAE (grade 3-4) | 0.95 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
| Colitis TRAE (grade 3-4) | 11.13 [3.56, 34.72] | | < 1 | | 0% | 5 studies (5/-) | 0.0 % | low | serious | high | non important | - |
| Cough TRAE (grade 3-4) | 0.95 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
| Decreased appetite TRAE (grade 3-4) | 0.95 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
| Diabetes TRAE (grade 3-4) | 2.07 [0.46, 9.33] | | < 1 | | 0% | 5 studies (5/-) | 17.3 % | low | not evaluable | high | non important | - |
| Diarrhoea TRAE (grade 3-4) | 1.57 [0.20, 12.16] | | < 1 | | 87% | 6 studies (6/-) | 33.4 % | low | not evaluable | high | non important | - |
| Dizziness TRAE (grade 3-4) | 0.95 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
| Dry skin TRAE (grade 3-4) | 0.95 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
| Dysgeusia TRAE (grade 3-4) | 0.95 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
| Dyspepsia TRAE (grade 3-4) | 0.95 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
| Dyspnoea TRAE (grade 3-4) | 1.19 [0.18, 7.88] | | < 1 | | 0% | 4 studies (4/-) | 42.8 % | low | not evaluable | high | non important | - |
| Ear and labyrinth disorders TRAE (grade 3-4) | 0.97 [0.06, 15.73] | | < 1 | | 0% | 2 studies (2/-) | 50.8 % | low | not evaluable | high | non important | - |
| Endocrine disorders TRAE (grade 3-4) | 12.40 [4.02, 38.27] | | < 1 | | 0% | 5 studies (5/-) | 0.0 % | low | not evaluable | high | non important | - |
| Eye disorders TRAE (grade 3-4) | 1.59 [0.20, 12.46] | | < 1 | | 0% | 3 studies (3/-) | 33.0 % | low | not evaluable | high | non important | - |
| Fatigue TRAE (grade 3-4) | 0.63 [0.16, 2.46] | | < 1 | | 0% | 4 studies (4/-) | 74.7 % | low | not evaluable | high | non important | - |
| Gastritis TRAE (grade 3-4) | 2.81 [0.41, 19.25] | | < 1 | | 0% | 3 studies (3/-) | 14.8 % | low | not evaluable | high | non important | - |
| Gastrointestinal disorders TRAE (grade 3-4) | 3.72 [0.30, 46.65] | | < 1 | | 94% | 6 studies (6/-) | 15.7 % | low | not evaluable | high | non important | - |
| General disorders and administration site conditions TRAE (grade 3-4) | 2.81 [0.41, 19.25] | | < 1 | | 0% | 3 studies (3/-) | 14.8 % | low | not evaluable | high | non important | - |
| Headache TRAE (grade 3-4) | 0.34 [0.07, 1.59] | | < 1 | | 0% | 4 studies (4/-) | 91.4 % | low | not evaluable | high | non important | - |
| Hepatitis TRAE (grade 3-4) | 5.00 [1.65, 15.13] | | < 1 | | 0% | 4 studies (4/-) | 0.2 % | low | not evaluable | high | non important | - |
| Hepatobiliary disorders TRAE (grade 3-4) | 5.34 [0.33, 87.00] | | < 1 | | 92% | 5 studies (5/-) | 12.2 % | low | serious | high | non important | - |
| Hypersensitivity TRAE (grade 3-4) | 2.01 [0.07, 59.97] | | < 1 | | 0% | 1 study (1/-) | 34.6 % | NA | not evaluable | | non important | - |
| Hypertension TRAE (grade 3-4) | 0.95 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
| Hyperthyroidism TRAE (grade 3-4) | 2.46 [0.60, 10.11] | | < 1 | | 0% | 5 studies (5/-) | 10.7 % | low | not evaluable | high | non important | - |
| Hypophysitis TRAE (grade 3-4) | 1.69 [0.25, 11.50] | | < 1 | | 63% | 6 studies (6/-) | 29.6 % | low | not evaluable | high | non important | - |
| Hypothyroidism TRAE (grade 3-4) | 0.74 [0.16, 3.39] | | < 1 | | 0% | 5 studies (5/-) | 65.1 % | low | serious | high | non important | - |
| Increase AST TRAE (grade 3-4) | 1.91 [0.18, 20.24] | | < 1 | | 82% | 4 studies (4/-) | 29.7 % | low | not evaluable | high | non important | - |
| Increased ALT TRAE (grade 3-4) | 3.00 [0.25, 36.26] | | < 1 | | 88% | 4 studies (4/-) | 19.5 % | low | not evaluable | high | non important | - |
| Increased lipase level TRAE (grade 3-4) | 2.12 [0.91, 4.92] | | < 1 | | 0% | 3 studies (3/-) | 4.0 % | low | not evaluable | high | non important | - |
| Infusion-related reactions TRAE (grade 3-4) | 0.95 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
| Leucopenia TRAE (grade 3-4) | 0.95 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
| Maculopapular rash TRAE (grade 3-4) | 0.53 [0.08, 3.37] | | < 1 | | 18% | 4 studies (4/-) | 74.8 % | low | not evaluable | high | non important | - |
| Metabolism and nutrition disorders TRAE (grade 3-4) | 1.44 [0.23, 8.93] | | < 1 | | 0% | 3 studies (3/-) | 35.0 % | low | not evaluable | high | non important | - |
| Musculoskeletal and connective tissue disorders TRAE (grade 3-4) | 0.95 [0.11, 8.51] | | < 1 | | 25% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
| Myalgia TRAE (grade 3-4) | 0.95 [0.12, 7.47] | | < 1 | | 0% | 3 studies (3/-) | 51.8 % | low | not evaluable | high | non important | - |
| Myocarditis TRAE (grade 3-4) | 1.97 [0.07, 58.99] | | < 1 | | 0% | 1 study (1/-) | 34.9 % | NA | not evaluable | | non important | - |
| Myositis TRAE (grade 3-4) | 0.96 [0.13, 6.86] | | < 1 | | 0% | 4 studies (4/-) | 51.6 % | low | not evaluable | high | non important | - |
| Nausea TRAE (grade 3-4) | 1.15 [0.21, 6.34] | | < 1 | | 0% | 5 studies (5/-) | 43.5 % | low | serious | high | non important | - |
| Nephritis TRAE (grade 3-4) | 3.96 [0.18, 87.96] | | < 1 | | 0% | 1 study (1/-) | 19.5 % | NA | not evaluable | | non important | - |
| Nervous system disorders TRAE (grade 3-4) | 2.54 [0.51, 12.65] | | < 1 | | 18% | 4 studies (4/-) | 12.8 % | low | not evaluable | high | non important | - |
| Neutropenia TRAE (grade 3-4) | 0.95 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
| Palmar-plantar erythrodysaesthesia syndrome TRAE (grade 3-4) | 0.95 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
| Pancreatitis TRAE (grade 3-4) | 0.96 [0.17, 5.60] | | < 1 | | 0% | 4 studies (4/-) | 51.6 % | low | not evaluable | high | non important | - |
| Paraesthesia TRAE (grade 3-4) | 0.95 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
| Peripheral neuropathy TRAE (grade 3-4) | 1.59 [0.20, 12.46] | | < 1 | | 0% | 3 studies (3/-) | 33.0 % | low | not evaluable | high | non important | - |
| Pneumonitis TRAE (grade 3-4) | 2.10 [0.35, 12.71] | | < 1 | | 0% | 4 studies (4/-) | 21.0 % | low | not evaluable | high | non important | - |
| Pruritus TRAE (grade 3-4) | 0.47 [0.09, 2.40] | | < 1 | | 0% | 5 studies (5/-) | 81.7 % | low | serious | high | non important | - |
| Pyrexia TRAE (grade 3-4) | 1.43 [0.28, 7.35] | | < 1 | | 0% | 4 studies (4/-) | 33.4 % | low | not evaluable | high | non important | - |
| Rash TRAE (grade 3-4) | 1.34 [0.15, 12.06] | | < 1 | | 61% | 3 studies (3/-) | 39.6 % | low | not evaluable | high | non important | - |
| Renal and urinary disorders TRAE (grade 3-4) | 1.00 [0.02, 50.62] | | < 1 | | 0% | 1 study (1/-) | 50.0 % | NA | not evaluable | | non important | - |
| Respiratory, thoracic and mediastinal disorders TRAE (grade 3-4) | 0.97 [0.21, 4.52] | | < 1 | | 0% | 5 studies (5/-) | 51.3 % | low | not evaluable | high | non important | - |
| Sarcoidosis TRAE (grade 3-4) | 0.96 [0.13, 6.86] | | < 1 | | 0% | 4 studies (4/-) | 51.6 % | low | not evaluable | high | non important | - |
| Severe skin reaction TRAE (grade 3-4) | 5.95 [0.30, 119.02] | | < 1 | | 0% | 1 study (1/-) | 12.5 % | NA | not evaluable | | non important | - |
| Skin and subcutaneous tissue disorders TRAE (grade 3-4) | 2.38 [0.33, 16.95] | | < 1 | | 75% | 6 studies (6/-) | 19.5 % | low | serious | high | non important | - |
| Stomatitis TRAE (grade 3-4) | 0.95 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
| Thrombocytopenia TRAE (grade 3-4) | 1.59 [0.20, 12.46] | | < 1 | | 0% | 3 studies (3/-) | 33.0 % | low | not evaluable | high | non important | - |
| Thyroiditis TRAE (grade 3-4) | 0.96 [0.13, 6.86] | | < 1 | | 0% | 4 studies (4/-) | 51.6 % | low | not evaluable | high | non important | - |
| Uveitis TRAE (grade 3-4) | 0.96 [0.13, 6.86] | | < 1 | | 0% | 4 studies (4/-) | 51.6 % | low | not evaluable | high | non important | - |
| Vitiligo TRAE (grade 3-4) | 0.96 [0.13, 6.86] | | < 1 | | 0% | 4 studies (4/-) | 51.6 % | low | not evaluable | high | non important | - |
| Vomiting TRAE (grade 3-4) | 0.95 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
| Weight decreased TRAE (grade 3-4) | 0.95 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.7 % | low | not evaluable | high | non important | - |
AE (grade 3-4) endpoints 00 |
| Abdominal pain AE (grade 3-4) | 0.04 [0.01, 0.17] | | < 1 | | 0% | 1 study (1/-) | 100.0 % | NA | not evaluable | | non important | - |
| Colitis AE (grade 3-4) | 6.26 [2.61, 15.03] | | < 1 | | 0% | 1 study (1/-) | 0.0 % | NA | not evaluable | | non important | - |
| Cough AE (grade 3-4) | 0.01 [0.00, 0.15] | | < 1 | | 0% | 1 study (1/-) | 99.9 % | NA | not evaluable | | non important | - |
| Decreased appetite AE (grade 3-4) | 0.06 [0.01, 0.46] | | < 1 | | 0% | 1 study (1/-) | 99.6 % | NA | not evaluable | | non important | - |
| Diarrhoea AE (grade 3-4) | 0.26 [0.18, 0.37] | | < 1 | | 0% | 1 study (1/-) | 100.0 % | NA | not evaluable | | non important | - |
| Fatigue AE (grade 3-4) | 0.05 [0.03, 0.10] | | < 1 | | 0% | 1 study (1/-) | 100.0 % | NA | not evaluable | | non important | - |
| Headache AE (grade 3-4) | 0.04 [0.01, 0.11] | | < 1 | | 0% | 1 study (1/-) | 100.0 % | NA | not evaluable | | non important | - |
| Hypophysitis AE (grade 3-4) | 11.01 [2.57, 47.24] | | < 1 | | 0% | 1 study (1/-) | 0.1 % | NA | not evaluable | | non important | - |
| Hypothyroidism AE (grade 3-4) | 0.14 [0.02, 1.16] | | < 1 | | 0% | 1 study (1/-) | 96.5 % | NA | not evaluable | | non important | - |
