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) | 0.84 [0.76, 0.93] | | < 1 | | 28% | 6 studies (6/-) | 100.0 % | 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) | 1.03 [0.91, 1.17] | | < 1 | | 61% | 6 studies (6/-) | 30.3 % | 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) | 1.01 [0.62, 1.65] | | > 1 | | 84% | 6 studies (6/-) | 52.2 % | 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 [0.25, 0.75] | | < 1 | | 57% | 3 studies (3/-) | 99.9 % | some concern | not evaluable | moderate | non important | - |
AE (grade 3-4) | 1.06 [0.84, 1.34] | | < 1 | | 20% | 3 studies (3/-) | 31.0 % | 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) | 1.16 [0.56, 2.38] | | < 1 | | 0% | 1 study (1/-) | 34.4 % | NA | not evaluable | | non important | - |
TRAE (any grade) | 0.26 [0.15, 0.45] | | < 1 | | 84% | 6 studies (6/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
TRAE (grade 3-4) | 0.35 [0.14, 0.89] | | < 1 | | 96% | 5 studies (5/-) | 98.6 % | some concern | not evaluable | moderate | non important | - |
TRAE leading to death (grade 5) | 1.22 [0.58, 2.57] | | < 1 | | 15% | 6 studies (6/-) | 30.0 % | 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 |
Acute kidney injury TRAE (grade 3-4) | 0.67 [0.06, 7.40] | | < 1 | | 0% | 2 studies (2/-) | 62.8 % | some concern | not evaluable | moderate | non important | - |
Adrenal insufficiency TRAE (grade 3-4) | 1.18 [0.19, 7.27] | | < 1 | | 0% | 4 studies (4/-) | 42.9 % | 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) | 0.19 [0.05, 0.78] | | < 1 | | 86% | 6 studies (6/-) | 99.0 % | 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) | 0.64 [0.26, 1.57] | | < 1 | | 28% | 6 studies (6/-) | 83.3 % | some concern | not evaluable | 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) | 1.30 [0.15, 11.18] | | < 1 | | 0% | 3 studies (3/-) | 40.5 % | some concern | not evaluable | moderate | 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) | 0.95 [0.02, 48.13] | | < 1 | | 0% | 1 study (1/-) | 51.0 % | NA | not evaluable | | non important | - |
Colitis TRAE (grade 3-4) | 0.92 [0.27, 3.19] | | < 1 | | 0% | 4 studies (4/-) | 55.2 % | some concern | not evaluable | moderate | non important | - |
Constipation TRAE (grade 3-4) | 0.74 [0.09, 6.36] | | < 1 | | 0% | 3 studies (3/-) | 60.7 % | some concern | not evaluable | moderate | non important | - |
Cough TRAE (grade 3-4) | 0.95 [0.02, 48.13] | | < 1 | | 0% | 1 study (1/-) | 51.0 % | NA | not evaluable | | non important | - |
Decreased appetite TRAE (grade 3-4) | 0.63 [0.20, 1.95] | | < 1 | | 40% | 5 studies (5/-) | 78.8 % | 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) | 0.54 [0.22, 1.32] | | < 1 | | 11% | 6 studies (6/-) | 91.3 % | some concern | not evaluable | moderate | 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 | - |
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) | 1.03 [0.51, 2.06] | | < 1 | | 34% | 6 studies (6/-) | 46.8 % | some concern | not evaluable | moderate | non important | - |
Febrile neutropenia TRAE (grade 3-4) | 0.05 [0.00, 0.79] | | < 1 | | 0% | 1 study (1/-) | 98.2 % | NA | not evaluable | | 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) | 0.47 [0.02, 14.21] | | < 1 | | 0% | 1 study (1/-) | 66.4 % | NA | not evaluable | | 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) | 0.95 [0.02, 48.13] | | < 1 | | 0% | 1 study (1/-) | 51.0 % | NA | not evaluable | | non important | - |
Hyperthyroidism TRAE (grade 3-4) | 1.02 [0.16, 6.74] | | < 1 | | 0% | 4 studies (4/-) | 49.0 % | 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 [0.19, 5.61] | | < 1 | | 0% | 5 studies (5/-) | 48.9 % | some concern | not evaluable | moderate | non important | - |
Increase AST TRAE (grade 3-4) | 0.35 [0.05, 2.48] | | < 1 | | 0% | 2 studies (2/-) | 85.3 % | some concern | not evaluable | moderate | non important | - |
Increased ALT TRAE (grade 3-4) | 0.45 [0.10, 1.98] | | < 1 | | 0% | 4 studies (4/-) | 85.4 % | some concern | not evaluable | moderate | non important | - |
Increased lipase level TRAE (grade 3-4) | 3.81 [0.20, 72.71] | | < 1 | | 0% | 1 study (1/-) | 19.0 % | NA | not evaluable | | non important | - |
Infusion-related reactions TRAE (grade 3-4) | 0.37 [0.13, 1.00] | | < 1 | | 0% | 4 studies (4/-) | 97.5 % | some concern | not evaluable | moderate | non important | - |
Leucopenia TRAE (grade 3-4) | 0.18 [0.06, 0.50] | | < 1 | | 25% | 6 studies (6/-) | 99.9 % | 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) | 0.45 [0.10, 2.11] | | < 1 | | 71% | 5 studies (5/-) | 84.4 % | 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) | 0.54 [0.17, 1.67] | | < 1 | | 24% | 6 studies (6/-) | 85.7 % | some concern | not evaluable | moderate | non important | - |
Nephritis TRAE (grade 3-4) | 2.32 [0.20, 26.51] | | < 1 | | 0% | 2 studies (2/-) | 25.0 % | 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) | 0.07 [0.01, 0.57] | | < 1 | | 85% | 5 studies (5/-) | 99.4 % | 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) | 0.16 [0.01, 3.15] | | < 1 | | 0% | 1 study (1/-) | 88.4 % | NA | not evaluable | | 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) | 0.38 [0.06, 2.57] | | < 1 | | 0% | 2 studies (2/-) | 83.8 % | some concern | not evaluable | moderate | non important | - |
Peripheral oedema TRAE (grade 3-4) | 1.91 [0.06, 57.09] | | < 1 | | 0% | 1 study (1/-) | 35.7 % | NA | not evaluable | | non important | - |
Pneumonitis TRAE (grade 3-4) | 2.56 [0.91, 7.16] | | < 1 | | 0% | 4 studies (4/-) | 3.7 % | 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) | 0.26 [0.02, 2.98] | | < 1 | | 0% | 2 studies (2/-) | 85.9 % | some concern | not evaluable | moderate | non important | - |
Rash TRAE (grade 3-4) | 0.18 [0.06, 0.55] | | < 1 | | 11% | 5 studies (5/-) | 99.9 % | 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) | 0.24 [0.01, 5.27] | | < 1 | | 0% | 1 study (1/-) | 81.6 % | NA | not evaluable | | 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) | 0.46 [0.07, 3.23] | | < 1 | | 73% | 5 studies (5/-) | 78.1 % | some concern | not evaluable | moderate | non important | - |
Thrombocytopenia TRAE (grade 3-4) | 0.35 [0.09, 1.42] | | < 1 | | 64% | 6 studies (6/-) | 92.9 % | 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) | 0.47 [0.01, 23.80] | | < 1 | | 0% | 1 study (1/-) | 64.4 % | NA | not evaluable | | non important | - |
Uveitis TRAE (grade 3-4) | 1.00 [0.06, 15.99] | | < 1 | | 0% | 2 studies (2/-) | 50.1 % | some concern | not evaluable | moderate | non important | - |
Vascular disorders TRAE (grade 3-4) | 0.95 [0.02, 48.13] | | < 1 | | 0% | 1 study (1/-) | 51.0 % | NA | not evaluable | | non important | - |
Vomiting TRAE (grade 3-4) | 0.52 [0.04, 7.08] | | < 1 | | 66% | 2 studies (2/-) | 68.6 % | some concern | not evaluable | moderate | non important | - |