| 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, 0.95] | | < 1 | | 21% | 7 studies (7/-) | 99.9 % | 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) | 0.92 [0.76, 1.12] | | < 1 | | 78% | 6 studies (6/-) | 79.5 % | 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 | 0.50 [0.20, 1.24] | | < 1 | | 91% | 5 studies (5/-) | 93.3 % | some concern | not evaluable | moderate | non important | - |
| objective responses (ORR) | 0.82 [0.50, 1.33] | | > 1 | | 93% | 7 studies (7/-) | 20.8 % | 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) | 0.46 [0.23, 0.92] | | < 1 | | 95% | 5 studies (5/-) | 98.6 % | 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) | 0.63 [0.34, 1.17] | | < 1 | | 94% | 7 studies (7/-) | 92.7 % | 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) | 0.95 [0.82, 1.10] | | < 1 | | 8% | 4 studies (4/-) | 75.2 % | some concern | not evaluable | moderate | non important | - |
| STRAE (any grade) | 0.65 [0.41, 1.02] | | < 1 | | 89% | 6 studies (6/-) | 97.1 % | some concern | serious | moderate | non important | - |
| TRAE (any grade) | 0.18 [0.09, 0.35] | | < 1 | | 91% | 6 studies (6/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
| TRAE (grade 3-4) | 0.22 [0.09, 0.57] | | < 1 | | 98% | 7 studies (7/-) | 99.9 % | some concern | not evaluable | moderate | non important | - |
| TRAE leading to death (grade 5) | 0.96 [0.55, 1.71] | | < 1 | | 0% | 7 studies (7/-) | 54.9 % | some concern | not evaluable | moderate | non important | - |
| TRAE leading to discontinuation (any grade) | 0.36 [0.22, 0.60] | | < 1 | | 56% | 3 studies (3/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
TRAE (grade 3-4) endpoints 00 |
| Abdominal pain TRAE (grade 3-4) | 3.64 [0.16, 81.12] | | < 1 | | 0% | 1 study (1/-) | 21.0 % | NA | not evaluable | | non important | - |
| Acute kidney injury TRAE (grade 3-4) | 0.45 [0.02, 13.55] | | < 1 | | 0% | 1 study (1/-) | 67.4 % | NA | not evaluable | | non important | - |
| Adrenal insufficiency TRAE (grade 3-4) | 1.47 [0.24, 9.04] | | < 1 | | 0% | 4 studies (4/-) | 34.0 % | some concern | not evaluable | moderate | non important | - |
| Alopecia TRAE (grade 3-4) | 0.60 [0.06, 5.94] | | < 1 | | 0% | 2 studies (2/-) | 66.8 % | some concern | not evaluable | moderate | non important | - |
| Anaemia TRAE (grade 3-4) | 0.17 [0.06, 0.49] | | < 1 | | 93% | 7 studies (7/-) | 99.9 % | some concern | serious | moderate | non important | - |
| Arthralgia TRAE (grade 3-4) | 0.91 [0.02, 45.86] | | < 1 | | 0% | 1 study (1/-) | 51.9 % | NA | not evaluable | | non important | - |
| Arthritis TRAE (grade 3-4) | 0.91 [0.02, 45.86] | | < 1 | | 0% | 1 study (1/-) | 51.9 % | NA | not evaluable | | non important | - |
| Asthenia TRAE (grade 3-4) | 0.55 [0.27, 1.11] | | < 1 | | 57% | 7 studies (7/-) | 95.3 % | some concern | serious | moderate | non important | - |
| Blood creatinine increased TRAE (grade 3-4) | 0.45 [0.02, 13.55] | | < 1 | | 0% | 1 study (1/-) | 67.4 % | NA | not evaluable | | non important | - |
| Colitis TRAE (grade 3-4) | 3.06 [0.80, 11.68] | | < 1 | | 0% | 4 studies (4/-) | 5.2 % | some concern | not evaluable | moderate | non important | - |
| Constipation TRAE (grade 3-4) | 0.21 [0.04, 1.05] | | < 1 | | 38% | 5 studies (5/-) | 97.1 % | some concern | not evaluable | moderate | non important | - |
| Decreased appetite TRAE (grade 3-4) | 0.70 [0.29, 1.68] | | < 1 | | 0% | 6 studies (6/-) | 78.6 % | some concern | not evaluable | moderate | non important | - |
| Diabetes TRAE (grade 3-4) | 1.68 [0.22, 13.01] | | < 1 | | 0% | 3 studies (3/-) | 31.2 % | some concern | not evaluable | moderate | non important | - |
| Diarrhoea TRAE (grade 3-4) | 0.96 [0.47, 1.95] | | < 1 | | 0% | 4 studies (4/-) | 54.5 % | some concern | not evaluable | moderate | non important | - |
| Dyspnoea TRAE (grade 3-4) | 3.64 [0.16, 81.12] | | < 1 | | 0% | 1 study (1/-) | 21.0 % | NA | not evaluable | | non important | - |
| Fatigue TRAE (grade 3-4) | 0.55 [0.29, 1.05] | | < 1 | | 45% | 7 studies (7/-) | 96.5 % | some concern | not evaluable | moderate | non important | - |
| Febrile neutropenia TRAE (grade 3-4) | 0.06 [0.01, 0.30] | | < 1 | | 0% | 2 studies (2/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
| Gastritis TRAE (grade 3-4) | 0.91 [0.02, 45.86] | | < 1 | | 0% | 1 study (1/-) | 51.9 % | NA | not evaluable | | non important | - |
| Guillain-Barré syndrome TRAE (grade 3-4) | 1.82 [0.06, 54.35] | | < 1 | | 0% | 1 study (1/-) | 36.7 % | NA | not evaluable | | non important | - |
| Hepatitis TRAE (grade 3-4) | 3.07 [0.47, 19.99] | | < 1 | | 0% | 3 studies (3/-) | 12.2 % | some concern | not evaluable | moderate | non important | - |
| Hypersensitivity TRAE (grade 3-4) | 0.45 [0.02, 13.55] | | < 1 | | 0% | 1 study (1/-) | 67.4 % | NA | not evaluable | | non important | - |
| Hyperthyroidism TRAE (grade 3-4) | 1.23 [0.19, 8.07] | | < 1 | | 0% | 4 studies (4/-) | 41.6 % | some concern | not evaluable | moderate | non important | - |
| Hypophysitis TRAE (grade 3-4) | 2.72 [0.39, 19.09] | | < 1 | | 0% | 3 studies (3/-) | 15.9 % | some concern | not evaluable | moderate | non important | - |
| Hypothyroidism TRAE (grade 3-4) | 2.25 [0.31, 16.26] | | < 1 | | 0% | 3 studies (3/-) | 21.2 % | some concern | not evaluable | moderate | non important | - |
| Increase AST TRAE (grade 3-4) | 0.91 [0.13, 6.48] | | < 1 | | 0% | 1 study (1/-) | 53.9 % | NA | not evaluable | | non important | - |
| Increased ALT TRAE (grade 3-4) | 2.74 [0.28, 26.45] | | < 1 | | 0% | 1 study (1/-) | 19.4 % | NA | not evaluable | | non important | - |
| Increased lipase level TRAE (grade 3-4) | 6.46 [0.79, 52.82] | | < 1 | | 0% | 1 study (1/-) | 4.2 % | NA | not evaluable | | non important | - |
| Infusion-related reactions TRAE (grade 3-4) | 0.93 [0.06, 14.94] | | < 1 | | 0% | 2 studies (2/-) | 52.0 % | some concern | not evaluable | moderate | non important | - |
| Leucopenia TRAE (grade 3-4) | 0.07 [0.00, 1.54] | | < 1 | | 84% | 3 studies (3/-) | 95.2 % | some concern | not evaluable | moderate | non important | - |
| Myocarditis TRAE (grade 3-4) | 2.19 [0.30, 15.87] | | < 1 | | 0% | 3 studies (3/-) | 21.9 % | some concern | not evaluable | moderate | non important | - |
| Myositis TRAE (grade 3-4) | 0.98 [0.16, 6.04] | | < 1 | | 0% | 4 studies (4/-) | 50.8 % | some concern | not evaluable | moderate | non important | - |
| Nausea TRAE (grade 3-4) | 0.50 [0.22, 1.14] | | < 1 | | 22% | 6 studies (6/-) | 95.0 % | some concern | not evaluable | moderate | non important | - |
| Nephritis TRAE (grade 3-4) | 2.89 [0.57, 14.59] | | < 1 | | 0% | 4 studies (4/-) | 10.1 % | some concern | not evaluable | moderate | non important | - |
| Neutropenia TRAE (grade 3-4) | 0.08 [0.02, 0.34] | | < 1 | | 91% | 7 studies (7/-) | 100.0 % | some concern | serious | moderate | non important | - |
| Pancreatitis TRAE (grade 3-4) | 2.93 [0.43, 19.90] | | < 1 | | 0% | 3 studies (3/-) | 13.7 % | some concern | not evaluable | moderate | non important | - |
| Pancytopenia TRAE (grade 3-4) | 0.11 [0.01, 2.13] | | < 1 | | 0% | 1 study (1/-) | 92.5 % | NA | not evaluable | | 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) | 4.44 [1.25, 15.74] | | < 1 | | 0% | 4 studies (4/-) | 1.1 % | some concern | not evaluable | moderate | non important | - |
| Pruritic rash TRAE (grade 3-4) | 0.91 [0.02, 45.86] | | < 1 | | 0% | 1 study (1/-) | 51.9 % | NA | not evaluable | | non important | - |
| Pruritus TRAE (grade 3-4) | 1.64 [0.40, 6.73] | | < 1 | | 0% | 6 studies (6/-) | 24.7 % | some concern | not evaluable | moderate | non important | - |
| Pyrexia TRAE (grade 3-4) | 0.23 [0.01, 5.02] | | < 1 | | 0% | 1 study (1/-) | 82.3 % | NA | not evaluable | | non important | - |
| Rash TRAE (grade 3-4) | 2.48 [0.66, 9.36] | | < 1 | | 0% | 5 studies (5/-) | 9.1 % | 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) | 0.91 [0.06, 14.56] | | < 1 | | 0% | 1 study (1/-) | 52.7 % | NA | not evaluable | | 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) | 1.82 [0.06, 54.35] | | < 1 | | 0% | 1 study (1/-) | 36.7 % | NA | not evaluable | | non important | - |
| Stomatitis TRAE (grade 3-4) | 0.91 [0.02, 45.86] | | < 1 | | 0% | 1 study (1/-) | 51.9 % | NA | not evaluable | | non important | - |
| Thrombocytopenia TRAE (grade 3-4) | 0.20 [0.05, 0.71] | | < 1 | | 85% | 5 studies (5/-) | 99.4 % | some concern | serious | moderate | non important | - |
| Thyroiditis TRAE (grade 3-4) | 1.24 [0.19, 8.17] | | < 1 | | 0% | 4 studies (4/-) | 41.2 % | some concern | not evaluable | moderate | non important | - |
| Vomiting TRAE (grade 3-4) | 0.34 [0.06, 1.92] | | < 1 | | 60% | 3 studies (3/-) | 88.9 % | 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 | - |
