| 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) | 0.87 [0.77, 0.99] | | < 1 | | 53% | 7 studies (7/-) | 98.5 % | some concern | not evaluable | moderate | crucial | - |
| deaths (OS) (extension) | 0.72 [0.64, 0.81] | | < 1 | | 0% | 3 studies (3/-) | 100.0 % | some concern | not evaluable | moderate | important | - |
| PFS (extension) | 0.87 [0.68, 1.11] | | < 1 | | 0% | 1 study (1/-) | 86.7 % | NA | not evaluable | | important | - |
| progression or deaths (PFS) | 1.05 [0.94, 1.18] | | < 1 | | 57% | 7 studies (7/-) | 19.4 % | some concern | not evaluable | moderate | important | - |
| DCR | 1.06 [0.77, 1.46] | | > 1 | | 0% | 2 studies (2/-) | 64.0 % | some concern | not evaluable | moderate | non important | - |
| objective responses (ORR) | 0.99 [0.67, 1.47] | | > 1 | | 81% | 7 studies (7/-) | 48.7 % | some concern | not evaluable | moderate | non important | - |
| objective responses (ORR) (extension) | 2.51 [1.07, 5.86] | | > 1 | | 0% | 1 study (1/-) | 98.3 % | NA | not evaluable | | non important | - |
safety endpoints 00 |
| AE (any grade) | 0.44 [0.27, 0.71] | | < 1 | | 41% | 4 studies (4/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
| AE (grade 3-4) | 1.15 [0.90, 1.47] | | < 1 | | 39% | 4 studies (4/-) | 12.6 % | some concern | not evaluable | moderate | non important | - |
| AE leading to death (grade 5) | 1.08 [0.80, 1.45] | | < 1 | | 0% | 4 studies (4/-) | 30.9 % | some concern | not evaluable | moderate | non important | - |
| AE leading to treatment discontinuation (any grade) | 0.90 [0.46, 1.78] | | < 1 | | 88% | 4 studies (4/-) | 61.6 % | some concern | not evaluable | moderate | non important | - |
| SAE (any grade) | 1.30 [0.98, 1.72] | | < 1 | | 0% | 2 studies (2/-) | 3.6 % | some concern | not evaluable | moderate | non important | - |
| STRAE (any grade) | 1.19 [0.89, 1.59] | | < 1 | | 0% | 2 studies (2/-) | 12.2 % | low | not evaluable | high | non important | - |
| TRAE (any grade) | 0.29 [0.17, 0.48] | | < 1 | | 82% | 7 studies (7/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
| TRAE (grade 3-4) | 0.44 [0.18, 1.07] | | < 1 | | 96% | 6 studies (6/-) | 96.5 % | some concern | not evaluable | moderate | non important | - |
| TRAE leading to death (grade 5) | 1.24 [0.66, 2.32] | | < 1 | | 1% | 7 studies (7/-) | 25.0 % | some concern | not evaluable | moderate | non important | - |
| TRAE leading to discontinuation (any grade) | 0.86 [0.55, 1.32] | | < 1 | | 0% | 4 studies (4/-) | 75.9 % | some concern | not evaluable | moderate | non important | - |
| TRAE leading to discontinuation (grade 3-4) | 1.28 [0.53, 3.10] | | < 1 | | 0% | 1 study (1/-) | 29.1 % | NA | not evaluable | | non important | - |
TRAE (grade 3-4) endpoints 00 |
| Abdominal pain TRAE (grade 3-4) | 0.49 [0.02, 14.76] | | < 1 | | 0% | 1 study (1/-) | 65.6 % | NA | not evaluable | | non important | - |
| Acute kidney injury TRAE (grade 3-4) | 1.14 [0.48, 2.75] | | < 1 | | 0% | 3 studies (3/-) | 38.2 % | low | not evaluable | high | non important | - |
| Adrenal insufficiency TRAE (grade 3-4) | 0.97 [0.20, 4.83] | | < 1 | | 0% | 5 studies (5/-) | 51.4 % | some concern | not evaluable | moderate | non important | - |
| Alopecia TRAE (grade 3-4) | 0.98 [0.10, 9.44] | | < 1 | | 0% | 3 studies (3/-) | 50.7 % | some concern | not evaluable | moderate | non important | - |
| Anaemia TRAE (grade 3-4) | 0.30 [0.12, 0.73] | | < 1 | | 84% | 7 studies (7/-) | 99.6 % | some concern | serious | moderate | non important | - |
| Arthralgia TRAE (grade 3-4) | 0.95 [0.02, 48.13] | | < 1 | | 0% | 1 study (1/-) | 51.0 % | NA | not evaluable | | non important | - |
| Asthenia TRAE (grade 3-4) | 0.84 [0.41, 1.72] | | < 1 | | 28% | 7 studies (7/-) | 68.6 % | some concern | serious | moderate | non important | - |
| Blood and lymphatic system disorders TRAE (grade 3-4) | 0.12 [0.01, 2.59] | | < 1 | | 97% | 3 studies (3/-) | 91.0 % | some concern | not evaluable | moderate | non important | - |
| Blood creatinine increased TRAE (grade 3-4) | 1.37 [0.50, 3.80] | | < 1 | | 0% | 4 studies (4/-) | 27.2 % | low | not evaluable | high | non important | - |
| Cardiac disorders TRAE (grade 3-4) | 0.95 [0.02, 48.13] | | < 1 | | 0% | 1 study (1/-) | 51.0 % | NA | not evaluable | | non important | - |
| Chills TRAE (grade 3-4) | 1.45 [0.11, 18.87] | | < 1 | | 0% | 2 studies (2/-) | 39.0 % | low | not evaluable | high | non important | - |
| Colitis TRAE (grade 3-4) | 0.77 [0.24, 2.43] | | < 1 | | 0% | 5 studies (5/-) | 67.4 % | some concern | not evaluable | moderate | non important | - |
| Constipation TRAE (grade 3-4) | 0.98 [0.16, 6.04] | | < 1 | | 0% | 4 studies (4/-) | 50.8 % | some concern | not evaluable | moderate | non important | - |
| Cough TRAE (grade 3-4) | 1.45 [0.11, 18.87] | | < 1 | | 0% | 2 studies (2/-) | 39.0 % | low | not evaluable | high | non important | - |
| Decreased appetite TRAE (grade 3-4) | 0.93 [0.45, 1.90] | | < 1 | | 33% | 6 studies (6/-) | 58.2 % | some concern | not evaluable | moderate | non important | - |
| Dermatitis acneiform TRAE (grade 3-4) | 0.99 [0.06, 15.94] | | < 1 | | 0% | 2 studies (2/-) | 50.2 % | some concern | not evaluable | moderate | non important | - |
| Diarrhoea TRAE (grade 3-4) | 0.60 [0.28, 1.29] | | < 1 | | 0% | 7 studies (7/-) | 90.5 % | some concern | not evaluable | moderate | non important | - |
| Dysgeusia TRAE (grade 3-4) | 0.25 [0.01, 5.48] | | < 1 | | 0% | 1 study (1/-) | 80.9 % | NA | not evaluable | | non important | - |
| Dyspepsia TRAE (grade 3-4) | 0.95 [0.02, 48.13] | | < 1 | | 0% | 1 study (1/-) | 51.0 % | NA | not evaluable | | non important | - |
| Dysphonia TRAE (grade 3-4) | 0.99 [0.02, 49.96] | | < 1 | | 0% | 1 study (1/-) | 50.2 % | NA | not evaluable | | non important | - |
| Dyspnoea TRAE (grade 3-4) | 3.83 [0.17, 85.33] | | < 1 | | 0% | 1 study (1/-) | 20.1 % | NA | not evaluable | | non important | - |
| Eczema TRAE (grade 3-4) | 0.47 [0.01, 23.80] | | < 1 | | 0% | 1 study (1/-) | 64.4 % | NA | not evaluable | | non important | - |
| Endocrine disorders TRAE (grade 3-4) | 2.30 [0.45, 11.90] | | < 1 | | 0% | 4 studies (4/-) | 16.1 % | some concern | not evaluable | moderate | non important | - |
| Epistaxis TRAE (grade 3-4) | 0.95 [0.02, 48.13] | | < 1 | | 0% | 1 study (1/-) | 51.0 % | NA | not evaluable | | non important | - |
| Erythema TRAE (grade 3-4) | 0.23 [0.01, 7.01] | | < 1 | | 0% | 1 study (1/-) | 79.5 % | NA | not evaluable | | non important | - |
| Eye disorders TRAE (grade 3-4) | 0.95 [0.02, 48.13] | | < 1 | | 0% | 1 study (1/-) | 51.0 % | NA | not evaluable | | non important | - |
| Fatigue TRAE (grade 3-4) | 1.09 [0.65, 1.83] | | < 1 | | 20% | 7 studies (7/-) | 37.0 % | some concern | not evaluable | moderate | non important | - |
| Febrile neutropenia TRAE (grade 3-4) | 0.26 [0.02, 3.80] | | < 1 | | 70% | 2 studies (2/-) | 83.6 % | low | not evaluable | high | non important | - |
| Gastritis TRAE (grade 3-4) | 0.95 [0.02, 48.13] | | < 1 | | 0% | 1 study (1/-) | 51.0 % | NA | not evaluable | | non important | - |
| Gastrointestinal disorders TRAE (grade 3-4) | 0.18 [0.06, 0.57] | | < 1 | | 56% | 3 studies (3/-) | 99.8 % | some concern | not evaluable | moderate | non important | - |
| General disorders and administration site conditions TRAE (grade 3-4) | 0.61 [0.15, 2.52] | | < 1 | | 90% | 3 studies (3/-) | 75.2 % | some concern | not evaluable | moderate | non important | - |
| Guillain-Barré syndrome TRAE (grade 3-4) | 1.91 [0.06, 57.09] | | < 1 | | 0% | 1 study (1/-) | 35.7 % | NA | not evaluable | | non important | - |
| Headache TRAE (grade 3-4) | 0.97 [0.09, 10.72] | | < 1 | | 0% | 2 studies (2/-) | 51.0 % | low | not evaluable | high | non important | - |
| Hepatitis TRAE (grade 3-4) | 2.59 [0.39, 17.34] | | < 1 | | 0% | 3 studies (3/-) | 16.4 % | some concern | not evaluable | moderate | non important | - |
| Hepatobiliary disorders TRAE (grade 3-4) | 0.94 [0.15, 5.84] | | < 1 | | 0% | 2 studies (2/-) | 52.4 % | some concern | not evaluable | moderate | non important | - |
| Hypersensitivity TRAE (grade 3-4) | 0.43 [0.03, 5.58] | | < 1 | | 0% | 2 studies (2/-) | 74.0 % | some concern | not evaluable | moderate | non important | - |
| Hypertension TRAE (grade 3-4) | 1.77 [0.37, 8.44] | | < 1 | | 0% | 2 studies (2/-) | 23.8 % | low | not evaluable | high | non important | - |
| Hyperthyroidism TRAE (grade 3-4) | 1.32 [0.30, 5.80] | | < 1 | | 0% | 5 studies (5/-) | 35.9 % | some concern | not evaluable | moderate | non important | - |
| Hypophysitis TRAE (grade 3-4) | 1.55 [0.22, 11.07] | | < 1 | | 0% | 3 studies (3/-) | 33.0 % | some concern | not evaluable | moderate | non important | - |
| Hypothyroidism TRAE (grade 3-4) | 1.02 [0.21, 4.85] | | < 1 | | 0% | 6 studies (6/-) | 49.1 % | some concern | serious | moderate | non important | - |
| Increase AST TRAE (grade 3-4) | 0.70 [0.15, 3.20] | | < 1 | | 0% | 3 studies (3/-) | 67.8 % | some concern | not evaluable | moderate | non important | - |
| Increased ALT TRAE (grade 3-4) | 1.00 [0.25, 4.06] | | < 1 | | 23% | 5 studies (5/-) | 49.9 % | some concern | serious | moderate | non important | - |
| Increased lipase level TRAE (grade 3-4) | 4.55 [0.80, 25.88] | | < 1 | | 0% | 2 studies (2/-) | 4.4 % | low | not evaluable | high | non important | - |
| Infusion-related reactions TRAE (grade 3-4) | 0.46 [0.18, 1.19] | | < 1 | | 0% | 5 studies (5/-) | 94.4 % | some concern | not evaluable | moderate | non important | - |
| Leucopenia TRAE (grade 3-4) | 0.27 [0.10, 0.73] | | < 1 | | 57% | 7 studies (7/-) | 99.5 % | some concern | serious | moderate | non important | - |
| Maculopapular rash TRAE (grade 3-4) | 0.47 [0.04, 6.17] | | < 1 | | 0% | 2 studies (2/-) | 71.5 % | some concern | not evaluable | moderate | non important | - |
| Metabolism and nutrition disorders TRAE (grade 3-4) | 0.47 [0.19, 1.17] | | < 1 | | 79% | 3 studies (3/-) | 94.8 % | some concern | not evaluable | moderate | non important | - |
| Mucosal inflammation TRAE (grade 3-4) | 0.70 [0.30, 1.63] | | < 1 | | 64% | 6 studies (6/-) | 79.8 % | some concern | not evaluable | moderate | non important | - |
| Musculoskeletal and connective tissue disorders TRAE (grade 3-4) | 1.91 [0.06, 57.09] | | < 1 | | 0% | 1 study (1/-) | 35.7 % | NA | not evaluable | | non important | - |
| Myalgia TRAE (grade 3-4) | 0.95 [0.02, 48.13] | | < 1 | | 0% | 1 study (1/-) | 51.0 % | NA | not evaluable | | non important | - |
| Myocarditis TRAE (grade 3-4) | 1.49 [0.11, 19.48] | | < 1 | | 0% | 2 studies (2/-) | 38.1 % | some concern | not evaluable | moderate | non important | - |
| Myositis TRAE (grade 3-4) | 0.50 [0.05, 5.51] | | < 1 | | 0% | 2 studies (2/-) | 71.4 % | some concern | not evaluable | moderate | non important | - |
| Nausea TRAE (grade 3-4) | 0.86 [0.44, 1.70] | | < 1 | | 23% | 7 studies (7/-) | 66.4 % | some concern | not evaluable | moderate | non important | - |
| Nephritis TRAE (grade 3-4) | 2.20 [0.30, 15.93] | | < 1 | | 0% | 3 studies (3/-) | 21.8 % | some concern | not evaluable | moderate | non important | - |
| Nervous system disorders TRAE (grade 3-4) | 0.47 [0.04, 5.26] | | < 1 | | 0% | 1 study (1/-) | 72.7 % | NA | not evaluable | | non important | - |
| Neutropenia TRAE (grade 3-4) | 0.21 [0.07, 0.60] | | < 1 | | 84% | 6 studies (6/-) | 99.8 % | some concern | serious | moderate | non important | - |
| Palmar-plantar erythrodysaesthesia syndrome TRAE (grade 3-4) | 0.43 [0.03, 5.58] | | < 1 | | 0% | 2 studies (2/-) | 74.0 % | some concern | not evaluable | moderate | non important | - |
| Pancreatitis TRAE (grade 3-4) | 1.49 [0.11, 19.48] | | < 1 | | 0% | 2 studies (2/-) | 38.1 % | some concern | not evaluable | moderate | non important | - |
| Pancytopenia TRAE (grade 3-4) | 0.49 [0.04, 5.79] | | < 1 | | 17% | 2 studies (2/-) | 71.3 % | some concern | not evaluable | moderate | non important | - |
| Paraesthesia TRAE (grade 3-4) | 0.95 [0.02, 48.13] | | < 1 | | 0% | 1 study (1/-) | 51.0 % | NA | not evaluable | | non important | - |
| Peripheral neuropathy TRAE (grade 3-4) | 0.34 [0.07, 1.72] | | < 1 | | 0% | 3 studies (3/-) | 90.3 % | some concern | not evaluable | moderate | non important | - |
| Peripheral oedema TRAE (grade 3-4) | 0.97 [0.09, 10.72] | | < 1 | | 0% | 2 studies (2/-) | 51.0 % | low | not evaluable | high | non important | - |
| Pneumonia TRAE (grade 3-4) | 0.76 [0.28, 2.08] | | < 1 | | 0% | 1 study (1/-) | 70.1 % | NA | not evaluable | | non important | - |
| Pneumonitis TRAE (grade 3-4) | 2.98 [1.13, 7.85] | | < 1 | | 0% | 5 studies (5/-) | 1.4 % | some concern | not evaluable | moderate | non important | - |
| Pruritic rash TRAE (grade 3-4) | 0.95 [0.02, 48.13] | | < 1 | | 0% | 1 study (1/-) | 51.0 % | NA | not evaluable | | non important | - |
| Pruritus generalised TRAE (grade 3-4) | 0.95 [0.02, 48.13] | | < 1 | | 0% | 1 study (1/-) | 51.0 % | NA | not evaluable | | non important | - |
| Pruritus TRAE (grade 3-4) | 0.51 [0.08, 3.20] | | < 1 | | 0% | 4 studies (4/-) | 76.2 % | some concern | not evaluable | moderate | non important | - |
| Pyrexia TRAE (grade 3-4) | 0.36 [0.06, 1.99] | | < 1 | | 0% | 3 studies (3/-) | 87.8 % | low | not evaluable | high | non important | - |
| Rash TRAE (grade 3-4) | 0.25 [0.08, 0.81] | | < 1 | | 22% | 6 studies (6/-) | 98.9 % | some concern | serious | moderate | non important | - |
| Renal and urinary disorders TRAE (grade 3-4) | 1.05 [0.08, 13.66] | | < 1 | | 0% | 2 studies (2/-) | 48.7 % | some concern | not evaluable | moderate | non important | - |
| Respiratory, thoracic and mediastinal disorders TRAE (grade 3-4) | 1.50 [0.46, 4.88] | | < 1 | | 0% | 2 studies (2/-) | 25.3 % | some concern | not evaluable | moderate | non important | - |
| Sepsis TRAE (grade 3-4) | 0.37 [0.06, 2.50] | | < 1 | | 0% | 2 studies (2/-) | 84.4 % | low | not evaluable | high | non important | - |
| Severe skin reaction TRAE (grade 3-4) | 0.27 [0.12, 0.61] | | < 1 | | 30% | 3 studies (3/-) | 99.9 % | some concern | not evaluable | moderate | non important | - |
| Skin and subcutaneous tissue disorders TRAE (grade 3-4) | 0.17 [0.07, 0.39] | | < 1 | | 0% | 3 studies (3/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
| Skin exfoliation TRAE (grade 3-4) | 0.67 [0.04, 10.72] | | < 1 | | 0% | 2 studies (2/-) | 61.1 % | some concern | not evaluable | moderate | non important | - |
| Stevens-Johnson syndrome TRAE (grade 3-4) | 0.95 [0.02, 48.13] | | < 1 | | 0% | 1 study (1/-) | 51.0 % | NA | not evaluable | | non important | - |
| Stomatitis TRAE (grade 3-4) | 0.68 [0.23, 2.00] | | < 1 | | 67% | 6 studies (6/-) | 75.9 % | some concern | not evaluable | moderate | non important | - |
| Thrombocytopenia TRAE (grade 3-4) | 0.63 [0.14, 2.72] | | < 1 | | 83% | 7 studies (7/-) | 73.3 % | some concern | not evaluable | moderate | non important | - |
| Thyroiditis TRAE (grade 3-4) | 0.78 [0.08, 7.48] | | < 1 | | 0% | 3 studies (3/-) | 58.6 % | some concern | not evaluable | moderate | non important | - |
| Urticaria TRAE (grade 3-4) | 1.07 [0.08, 13.96] | | < 1 | | 0% | 2 studies (2/-) | 48.0 % | low | not evaluable | high | non important | - |
