| 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) | 0.88 [0.82, 0.94] | | < 1 | | 10% | 8 studies (8/-) | 100.0 % | some concern | not evaluable | moderate | crucial | - |
| deaths (OS) (extension) | 0.77 [0.66, 0.90] | | < 1 | | 38% | 2 studies (2/-) | 100.0 % | some concern | not evaluable | moderate | important | - |
| PFS (extension) | 0.96 [0.79, 1.16] | | < 1 | | 0% | 1 study (1/-) | 66.1 % | NA | not evaluable | | important | - |
| progression or deaths (PFS) | 0.95 [0.80, 1.14] | | < 1 | | 77% | 7 studies (7/-) | 69.3 % | some concern | not evaluable | moderate | important | - |
| CRR | 1.96 [1.21, 3.17] | | > 1 | | 0% | 1 study (1/-) | 99.7 % | NA | not evaluable | | non important | - |
| DOR | 0.49 [0.24, 1.00] | | < 1 | | 88% | 6 studies (6/-) | 97.5 % | some concern | not evaluable | moderate | non important | - |
| objective responses (ORR) | 0.78 [0.51, 1.20] | | > 1 | | 93% | 8 studies (8/-) | 12.9 % | some concern | not evaluable | moderate | non important | - |
| objective responses (ORR) (extension) | 2.16 [1.34, 3.48] | | > 1 | | 0% | 1 study (1/-) | 99.9 % | NA | not evaluable | | non important | - |
safety endpoints 00 |
| AE (any grade) | 0.36 [0.15, 0.88] | | < 1 | | 62% | 4 studies (4/-) | 98.7 % | some concern | not evaluable | moderate | non important | - |
| AE (grade 3-4) | 0.47 [0.27, 0.84] | | < 1 | | 94% | 6 studies (6/-) | 99.5 % | some concern | not evaluable | moderate | non important | - |
| AE (grade 3-5) | 0.76 [0.19, 3.00] | | < 1 | | 96% | 2 studies (2/-) | 65.4 % | some concern | not evaluable | moderate | non important | - |
| AE leading to death (grade 5) | 1.78 [1.15, 2.77] | | < 1 | | 58% | 6 studies (6/-) | 0.5 % | some concern | not evaluable | moderate | non important | - |
| AE leading to treatment discontinuation (any grade) | 0.71 [0.40, 1.24] | | < 1 | | 94% | 8 studies (8/-) | 88.9 % | some concern | not evaluable | moderate | non important | - |
| AE leading to treatment discontinuation (grade 3-4) | 0.85 [0.44, 1.65] | | < 1 | | 0% | 1 study (1/-) | 68.1 % | NA | not evaluable | | non important | - |
| SAE (any grade) | 1.06 [0.83, 1.34] | | < 1 | | 71% | 5 studies (5/-) | 32.3 % | some concern | not evaluable | moderate | non important | - |
| STRAE (any grade) | 0.73 [0.48, 1.13] | | < 1 | | 90% | 7 studies (7/-) | 91.8 % | some concern | not evaluable | moderate | non important | - |
| TRAE (any grade) | 0.19 [0.11, 0.35] | | < 1 | | 90% | 7 studies (7/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
| TRAE (grade 3-4) | 0.23 [0.10, 0.51] | | < 1 | | 98% | 8 studies (8/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
| TRAE leading to death (grade 5) | 1.00 [0.57, 1.74] | | < 1 | | 0% | 8 studies (8/-) | 50.2 % | some concern | not evaluable | moderate | non important | - |
| TRAE leading to discontinuation (any grade) | 0.51 [0.23, 1.12] | | < 1 | | 88% | 4 studies (4/-) | 95.4 % | some concern | not evaluable | moderate | non important | - |
TRAE (grade 3-4) endpoints 00 |
| Abdominal pain TRAE (grade 3-4) | 2.15 [0.19, 24.47] | | < 1 | | 0% | 2 studies (2/-) | 27.1 % | some concern | not evaluable | moderate | non important | - |
| Acute kidney injury TRAE (grade 3-4) | 1.59 [0.24, 10.48] | | < 1 | | 0% | 2 studies (2/-) | 31.6 % | some concern | not evaluable | moderate | non important | - |
| Adrenal insufficiency TRAE (grade 3-4) | 2.30 [0.49, 10.78] | | < 1 | | 0% | 5 studies (5/-) | 14.6 % | some concern | serious | moderate | non important | - |
| Alopecia TRAE (grade 3-4) | 0.67 [0.09, 4.84] | | < 1 | | 0% | 3 studies (3/-) | 65.4 % | some concern | not evaluable | moderate | non important | - |
| Anaemia TRAE (grade 3-4) | 0.13 [0.05, 0.39] | | < 1 | | 93% | 8 studies (8/-) | 100.0 % | some concern | serious | moderate | non important | - |
| Arthralgia TRAE (grade 3-4) | 2.85 [0.26, 30.86] | | < 1 | | 0% | 2 studies (2/-) | 19.6 % | some concern | not evaluable | moderate | non important | - |
| Arthritis TRAE (grade 3-4) | 1.36 [0.10, 17.75] | | < 1 | | 0% | 2 studies (2/-) | 40.8 % | some concern | not evaluable | moderate | non important | - |
| Asthenia TRAE (grade 3-4) | 0.58 [0.31, 1.05] | | < 1 | | 49% | 8 studies (8/-) | 96.3 % | some concern | serious | moderate | non important | - |
| Blood creatinine increased TRAE (grade 3-4) | 0.46 [0.04, 5.04] | | < 1 | | 0% | 2 studies (2/-) | 73.7 % | some concern | not evaluable | moderate | non important | - |
| Colitis TRAE (grade 3-4) | 3.56 [1.05, 12.06] | | < 1 | | 0% | 5 studies (5/-) | 2.1 % | some concern | not evaluable | moderate | non important | - |
| Constipation TRAE (grade 3-4) | 0.29 [0.07, 1.23] | | < 1 | | 35% | 6 studies (6/-) | 95.3 % | some concern | not evaluable | moderate | non important | - |
| Decreased appetite TRAE (grade 3-4) | 0.70 [0.33, 1.49] | | < 1 | | 0% | 7 studies (7/-) | 82.4 % | some concern | not evaluable | moderate | non important | - |
| Diabetes TRAE (grade 3-4) | 1.72 [0.30, 9.94] | | < 1 | | 0% | 4 studies (4/-) | 27.3 % | some concern | not evaluable | moderate | non important | - |
| Diarrhoea TRAE (grade 3-4) | 1.13 [0.62, 2.05] | | < 1 | | 0% | 5 studies (5/-) | 34.5 % | some concern | not evaluable | moderate | non important | - |
| Dyspnoea TRAE (grade 3-4) | 2.15 [0.19, 24.47] | | < 1 | | 0% | 2 studies (2/-) | 27.1 % | some concern | not evaluable | moderate | non important | - |
| Fatigue TRAE (grade 3-4) | 0.57 [0.33, 0.99] | | < 1 | | 36% | 8 studies (8/-) | 97.8 % | some concern | not evaluable | moderate | non important | - |
| Febrile neutropenia TRAE (grade 3-4) | 0.10 [0.03, 0.39] | | < 1 | | 0% | 3 studies (3/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
| Gastritis TRAE (grade 3-4) | 1.36 [0.10, 17.75] | | < 1 | | 0% | 2 studies (2/-) | 40.8 % | some concern | not evaluable | moderate | non important | - |
| Guillain-Barré syndrome TRAE (grade 3-4) | 1.36 [0.10, 17.71] | | < 1 | | 0% | 2 studies (2/-) | 40.9 % | some concern | not evaluable | moderate | non important | - |
| Hepatitis TRAE (grade 3-4) | 2.72 [0.53, 14.06] | | < 1 | | 0% | 4 studies (4/-) | 11.7 % | some concern | not evaluable | moderate | non important | - |
| Hypersensitivity TRAE (grade 3-4) | 0.46 [0.04, 5.04] | | < 1 | | 0% | 2 studies (2/-) | 73.7 % | some concern | not evaluable | moderate | non important | - |
| Hyperthyroidism TRAE (grade 3-4) | 1.16 [0.21, 6.35] | | < 1 | | 0% | 5 studies (5/-) | 43.1 % | some concern | serious | moderate | non important | - |
| Hypophysitis TRAE (grade 3-4) | 3.36 [0.66, 17.24] | | < 1 | | 0% | 4 studies (4/-) | 7.4 % | some concern | not evaluable | moderate | non important | - |
| Hypothyroidism TRAE (grade 3-4) | 2.60 [0.49, 13.77] | | < 1 | | 0% | 4 studies (4/-) | 13.2 % | some concern | not evaluable | moderate | non important | - |
| Increase AST TRAE (grade 3-4) | 1.36 [0.38, 4.94] | | < 1 | | 0% | 2 studies (2/-) | 31.9 % | some concern | not evaluable | moderate | non important | - |
| Increased ALT TRAE (grade 3-4) | 2.76 [0.55, 13.71] | | < 1 | | 0% | 2 studies (2/-) | 10.8 % | some concern | not evaluable | moderate | non important | - |
| Increased lipase level TRAE (grade 3-4) | 10.14 [2.36, 43.58] | | < 1 | | 0% | 2 studies (2/-) | 0.1 % | some concern | not evaluable | moderate | non important | - |
| Infusion-related reactions TRAE (grade 3-4) | 0.93 [0.10, 8.94] | | < 1 | | 0% | 3 studies (3/-) | 52.5 % | some concern | not evaluable | moderate | non important | - |
| Leucopenia TRAE (grade 3-4) | 0.07 [0.01, 0.76] | | < 1 | | 81% | 4 studies (4/-) | 98.5 % | some concern | not evaluable | moderate | non important | - |
| Myocarditis TRAE (grade 3-4) | 1.84 [0.31, 10.77] | | < 1 | | 0% | 4 studies (4/-) | 25.0 % | some concern | not evaluable | moderate | non important | - |
| Myositis TRAE (grade 3-4) | 0.97 [0.19, 5.05] | | < 1 | | 0% | 5 studies (5/-) | 51.4 % | some concern | not evaluable | moderate | non important | - |
| Nausea TRAE (grade 3-4) | 0.40 [0.18, 0.93] | | < 1 | | 29% | 7 studies (7/-) | 98.4 % | some concern | serious | moderate | non important | - |
| Nephritis TRAE (grade 3-4) | 2.66 [0.62, 11.47] | | < 1 | | 0% | 5 studies (5/-) | 9.6 % | some concern | serious | moderate | non important | - |
| Neutropenia TRAE (grade 3-4) | 0.06 [0.01, 0.24] | | < 1 | | 91% | 8 studies (8/-) | 100.0 % | some concern | serious | moderate | non important | - |
| Pancreatitis TRAE (grade 3-4) | 3.13 [0.61, 15.95] | | < 1 | | 0% | 4 studies (4/-) | 8.6 % | some concern | not evaluable | moderate | non important | - |
| Pancytopenia TRAE (grade 3-4) | 0.11 [0.01, 0.91] | | < 1 | | 0% | 2 studies (2/-) | 97.9 % | some concern | not evaluable | moderate | non important | - |
| Peripheral neuropathy TRAE (grade 3-4) | 0.15 [0.03, 0.83] | | < 1 | | 0% | 2 studies (2/-) | 98.5 % | some concern | not evaluable | moderate | non important | - |
| Pneumonitis TRAE (grade 3-4) | 3.99 [1.22, 13.06] | | < 1 | | 0% | 5 studies (5/-) | 1.1 % | some concern | not evaluable | moderate | non important | - |
| Pruritic rash TRAE (grade 3-4) | 1.36 [0.10, 17.75] | | < 1 | | 0% | 2 studies (2/-) | 40.8 % | some concern | not evaluable | moderate | non important | - |
| Pruritus TRAE (grade 3-4) | 1.88 [0.52, 6.82] | | < 1 | | 0% | 7 studies (7/-) | 16.8 % | some concern | serious | moderate | non important | - |
| Pyrexia TRAE (grade 3-4) | 0.62 [0.12, 3.24] | | < 1 | | 0% | 2 studies (2/-) | 71.6 % | some concern | not evaluable | moderate | non important | - |
| Rash TRAE (grade 3-4) | 2.99 [0.89, 10.03] | | < 1 | | 0% | 6 studies (6/-) | 3.9 % | some concern | not evaluable | moderate | non important | - |
| Sarcoidosis TRAE (grade 3-4) | 1.05 [0.07, 16.88] | | < 1 | | 0% | 2 studies (2/-) | 48.5 % | some concern | not evaluable | moderate | non important | - |
| Sepsis TRAE (grade 3-4) | 0.69 [0.08, 5.93] | | < 1 | | 0% | 2 studies (2/-) | 63.1 % | some concern | not evaluable | moderate | non important | - |
| Severe skin reaction TRAE (grade 3-4) | 1.36 [0.32, 5.68] | | < 1 | | 41% | 3 studies (3/-) | 33.8 % | some concern | not evaluable | moderate | non important | - |
| Stevens-Johnson syndrome TRAE (grade 3-4) | 1.36 [0.10, 17.71] | | < 1 | | 0% | 2 studies (2/-) | 40.9 % | some concern | not evaluable | moderate | non important | - |
| Stomatitis TRAE (grade 3-4) | 1.36 [0.10, 17.75] | | < 1 | | 0% | 2 studies (2/-) | 40.8 % | some concern | not evaluable | moderate | non important | - |
| Thrombocytopenia TRAE (grade 3-4) | 0.14 [0.04, 0.51] | | < 1 | | 85% | 6 studies (6/-) | 99.8 % | some concern | serious | moderate | non important | - |
| Thyroiditis TRAE (grade 3-4) | 1.36 [0.26, 7.08] | | < 1 | | 0% | 5 studies (5/-) | 35.7 % | some concern | serious | moderate | non important | - |
| Vomiting TRAE (grade 3-4) | 0.40 [0.12, 1.27] | | < 1 | | 45% | 4 studies (4/-) | 94.0 % | some concern | not evaluable | moderate | non important | - |
AE (grade 3-4) endpoints 00 |
| Abdominal pain AE (grade 3-4) | 0.40 [0.10, 1.58] | | < 1 | | 0% | 1 study (1/-) | 90.3 % | NA | not evaluable | | non important | - |
| Acute kidney injury AE (grade 3-4) | 2.27 [0.58, 8.88] | | < 1 | | 0% | 1 study (1/-) | 12.0 % | NA | not evaluable | | non important | - |
| Alopecia AE (grade 3-4) | 0.16 [0.01, 3.17] | | < 1 | | 0% | 1 study (1/-) | 88.3 % | NA | not evaluable | | non important | - |
| Anaemia AE (grade 3-4) | 0.38 [0.08, 1.85] | | < 1 | | 97% | 3 studies (3/-) | 88.3 % | some concern | not evaluable | moderate | non important | - |
| Arthralgia AE (grade 3-4) | 0.16 [0.01, 3.17] | | < 1 | | 0% | 1 study (1/-) | 88.3 % | NA | not evaluable | | non important | - |
| Asthenia AE (grade 3-4) | 0.56 [0.18, 1.73] | | < 1 | | 81% | 3 studies (3/-) | 84.4 % | some concern | not evaluable | moderate | non important | - |
| Back pain AE (grade 3-4) | 1.92 [0.17, 21.35] | | < 1 | | 0% | 1 study (1/-) | 29.8 % | NA | not evaluable | | non important | - |
| Blood and lymphatic system disorders AE (grade 3-4) | 0.24 [0.15, 0.40] | | < 1 | | 0% | 1 study (1/-) | 100.0 % | NA | not evaluable | | non important | - |
| Blood creatinine increased AE (grade 3-4) | 1.92 [0.17, 21.35] | | < 1 | | 0% | 1 study (1/-) | 29.8 % | NA | not evaluable | | non important | - |
| Cardiac disorders AE (grade 3-4) | 0.72 [0.16, 3.23] | | < 1 | | 0% | 1 study (1/-) | 66.8 % | NA | not evaluable | | non important | - |
| Constipation AE (grade 3-4) | 0.35 [0.09, 1.34] | | < 1 | | 0% | 1 study (1/-) | 93.6 % | NA | not evaluable | | non important | - |
| Cough AE (grade 3-4) | 1.92 [0.06, 57.51] | | < 1 | | 0% | 1 study (1/-) | 35.5 % | NA | not evaluable | | non important | - |
| Decreased appetite AE (grade 3-4) | 3.28 [0.89, 12.06] | | < 1 | | 0% | 1 study (1/-) | 3.7 % | NA | not evaluable | | non important | - |
| Diarrhoea AE (grade 3-4) | 0.96 [0.24, 3.87] | | < 1 | | 0% | 1 study (1/-) | 52.4 % | NA | not evaluable | | non important | - |
| Dizziness AE (grade 3-4) | 0.48 [0.02, 14.32] | | < 1 | | 0% | 1 study (1/-) | 66.2 % | NA | not evaluable | | non important | - |
| Dry skin AE (grade 3-4) | 0.96 [0.02, 48.49] | | < 1 | | 0% | 1 study (1/-) | 50.8 % | NA | not evaluable | | non important | - |
| Dysgeusia AE (grade 3-4) | 0.96 [0.02, 48.49] | | < 1 | | 0% | 1 study (1/-) | 50.8 % | NA | not evaluable | | non important | - |
| Dyspnoea AE (grade 3-4) | 1.61 [0.38, 6.80] | | < 1 | | 0% | 1 study (1/-) | 25.9 % | NA | not evaluable | | non important | - |
| Endocrine disorders AE (grade 3-4) | 5.81 [0.29, 116.49] | | < 1 | | 0% | 1 study (1/-) | 12.8 % | NA | not evaluable | | non important | - |
| Eye disorders AE (grade 3-4) | 3.86 [0.17, 85.92] | | < 1 | | 0% | 1 study (1/-) | 20.0 % | NA | not evaluable | | non important | - |
| Fatigue AE (grade 3-4) | 0.48 [0.25, 0.91] | | < 1 | | 53% | 3 studies (3/-) | 98.8 % | some concern | not evaluable | moderate | non important | - |
| Febrile neutropenia AE (grade 3-4) | 0.16 [0.01, 3.75] | | < 1 | | 85% | 3 studies (3/-) | 86.8 % | some concern | not evaluable | moderate | non important | - |
| Gastrointestinal disorders AE (grade 3-4) | 0.42 [0.24, 0.75] | | < 1 | | 0% | 1 study (1/-) | 99.9 % | NA | not evaluable | | non important | - |
| General disorders and administration site conditions AE (grade 3-4) | 0.49 [0.28, 0.86] | | < 1 | | 0% | 1 study (1/-) | 99.4 % | NA | not evaluable | | non important | - |
| Headache AE (grade 3-4) | 1.92 [0.06, 57.51] | | < 1 | | 0% | 1 study (1/-) | 35.5 % | NA | not evaluable | | non important | - |
| Hypertension AE (grade 3-4) | 1.16 [0.29, 4.59] | | < 1 | | 77% | 2 studies (2/-) | 41.4 % | some concern | not evaluable | moderate | non important | - |
| Hypothyroidism AE (grade 3-4) | 0.96 [0.02, 48.49] | | < 1 | | 0% | 1 study (1/-) | 50.8 % | NA | not evaluable | | non important | - |
| Increase AST AE (grade 3-4) | 11.75 [0.65, 211.40] | | < 1 | | 0% | 1 study (1/-) | 4.9 % | NA | not evaluable | | non important | - |
