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) | 0.80 [0.72, 0.89] | | < 1 | | 8% | 4 studies (4/-) | 100.0 % | some concern | not evaluable | moderate | crucial | - |
deaths (OS) (extension) | 0.75 [0.61, 0.93] | | < 1 | | 0% | 1 study (1/-) | 99.6 % | NA | not evaluable | | important | - |
PFS (extension) | 0.79 [0.64, 0.97] | | < 1 | | 0% | 1 study (1/-) | 98.8 % | NA | not evaluable | | important | - |
progression or deaths (PFS) | 0.95 [0.82, 1.11] | | < 1 | | 63% | 4 studies (4/-) | 72.1 % | some concern | not evaluable | moderate | important | - |
objective responses (ORR) | 1.52 [0.95, 2.42] | | > 1 | | 70% | 4 studies (4/-) | 96.0 % | some concern | not evaluable | moderate | non important | - |
objective responses (ORR) (extension) | 4.80 [2.14, 10.77] | | > 1 | | 0% | 1 study (1/-) | 100.0 % | NA | not evaluable | | non important | - |
safety endpoints 00 |
AE (any grade) | 0.69 [0.42, 1.13] | | < 1 | | 0% | 2 studies (2/-) | 93.1 % | some concern | not evaluable | moderate | non important | - |
AE (grade 3-4) | 0.53 [0.43, 0.65] | | < 1 | | 0% | 2 studies (2/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
AE leading to death (grade 5) | 0.80 [0.40, 1.57] | | < 1 | | 0% | 2 studies (2/-) | 74.6 % | some concern | not evaluable | moderate | non important | - |
AE leading to treatment discontinuation (any grade) | 0.45 [0.24, 0.87] | | < 1 | | 66% | 2 studies (2/-) | 99.2 % | some concern | not evaluable | moderate | non important | - |
SAE (any grade) | 1.05 [0.64, 1.73] | | < 1 | | 0% | 1 study (1/-) | 42.1 % | NA | not evaluable | | non important | - |
SAE (grade 3-4) | 1.03 [0.80, 1.31] | | < 1 | | 0% | 1 study (1/-) | 42.1 % | NA | not evaluable | | non important | - |
STRAE (any grade) | 0.45 [0.28, 0.71] | | < 1 | | 42% | 2 studies (2/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
STRAE (grade 3-4) | 0.34 [0.18, 0.66] | | < 1 | | 0% | 1 study (1/-) | 99.9 % | NA | not evaluable | | non important | - |
TRAE (any grade) | 0.30 [0.25, 0.36] | | < 1 | | 0% | 4 studies (4/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
TRAE (grade 3-4) | 0.17 [0.12, 0.24] | | < 1 | | 61% | 4 studies (4/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
TRAE leading to death (grade 5) | 0.32 [0.13, 0.75] | | < 1 | | 0% | 4 studies (4/-) | 99.5 % | some concern | not evaluable | moderate | non important | - |
TRAE leading to discontinuation (any grade) | 0.35 [0.14, 0.87] | | < 1 | | 74% | 3 studies (3/-) | 98.8 % | some concern | not evaluable | moderate | non important | - |
TRAE leading to discontinuation (grade 3-4) | 0.80 [0.33, 1.95] | | < 1 | | 0% | 1 study (1/-) | 68.6 % | NA | not evaluable | | non important | - |
TRAE (grade 3-4) endpoints 00 |
Acute kidney injury TRAE (grade 3-4) | 0.66 [0.04, 10.50] | | < 1 | | 0% | 2 studies (2/-) | 61.6 % | some concern | not evaluable | moderate | non important | - |
Adrenal insufficiency TRAE (grade 3-4) | 1.86 [0.06, 55.60] | | < 1 | | 0% | 1 study (1/-) | 36.2 % | NA | not evaluable | | non important | - |
Alopecia TRAE (grade 3-4) | 0.66 [0.04, 10.50] | | < 1 | | 0% | 2 studies (2/-) | 61.6 % | some concern | not evaluable | moderate | non important | - |
Anaemia TRAE (grade 3-4) | 0.08 [0.01, 0.44] | | < 1 | | 0% | 2 studies (2/-) | 99.8 % | some concern | not evaluable | moderate | non important | - |
Arthralgia TRAE (grade 3-4) | 0.46 [0.02, 13.86] | | < 1 | | 0% | 1 study (1/-) | 66.9 % | NA | not evaluable | | non important | - |
Asthenia TRAE (grade 3-4) | 0.06 [0.01, 0.49] | | < 1 | | 0% | 1 study (1/-) | 99.6 % | NA | not evaluable | | non important | - |
Blood creatinine increased TRAE (grade 3-4) | 0.46 [0.01, 23.40] | | < 1 | | 0% | 1 study (1/-) | 64.7 % | NA | not evaluable | | non important | - |
Colitis TRAE (grade 3-4) | 1.67 [0.15, 19.05] | | < 1 | | 0% | 2 studies (2/-) | 34.1 % | some concern | not evaluable | moderate | non important | - |
Decreased appetite TRAE (grade 3-4) | 0.13 [0.01, 1.31] | | < 1 | | 0% | 2 studies (2/-) | 95.7 % | some concern | not evaluable | moderate | non important | - |
Diabetes TRAE (grade 3-4) | 0.46 [0.01, 23.40] | | < 1 | | 0% | 1 study (1/-) | 64.7 % | NA | not evaluable | | non important | - |
Diarrhoea TRAE (grade 3-4) | 0.28 [0.03, 2.60] | | < 1 | | 0% | 2 studies (2/-) | 86.7 % | some concern | not evaluable | moderate | non important | - |
Dyspnoea TRAE (grade 3-4) | 0.46 [0.04, 5.13] | | < 1 | | 0% | 1 study (1/-) | 73.3 % | NA | not evaluable | | non important | - |
Eczema TRAE (grade 3-4) | 0.46 [0.01, 23.40] | | < 1 | | 0% | 1 study (1/-) | 64.7 % | NA | not evaluable | | non important | - |
Endocrine disorders TRAE (grade 3-4) | 0.46 [0.01, 23.40] | | < 1 | | 0% | 1 study (1/-) | 64.7 % | NA | not evaluable | | non important | - |
Erythema TRAE (grade 3-4) | 0.46 [0.01, 23.40] | | < 1 | | 0% | 1 study (1/-) | 64.7 % | NA | not evaluable | | non important | - |
Fatigue TRAE (grade 3-4) | 0.19 [0.06, 0.62] | | < 1 | | 0% | 2 studies (2/-) | 99.7 % | some concern | not evaluable | moderate | non important | - |
Febrile neutropenia TRAE (grade 3-4) | 0.01 [0.00, 0.20] | | < 1 | | 0% | 1 study (1/-) | 99.9 % | NA | not evaluable | | non important | - |
Gastrointestinal disorders TRAE (grade 3-4) | 0.93 [0.03, 27.74] | | < 1 | | 0% | 1 study (1/-) | 51.8 % | NA | not evaluable | | non important | - |
Headache TRAE (grade 3-4) | 0.46 [0.02, 13.86] | | < 1 | | 0% | 1 study (1/-) | 66.9 % | NA | not evaluable | | non important | - |
Hepatobiliary disorders TRAE (grade 3-4) | 1.39 [0.14, 13.49] | | < 1 | | 0% | 1 study (1/-) | 38.8 % | NA | not evaluable | | non important | - |
Hypersensitivity TRAE (grade 3-4) | 0.33 [0.03, 3.62] | | < 1 | | 0% | 2 studies (2/-) | 81.7 % | some concern | not evaluable | moderate | non important | - |
Hypertension TRAE (grade 3-4) | 1.86 [0.17, 20.62] | | < 1 | | 0% | 1 study (1/-) | 30.8 % | NA | not evaluable | | non important | - |
Hyperthyroidism TRAE (grade 3-4) | 0.46 [0.01, 23.40] | | < 1 | | 0% | 1 study (1/-) | 64.7 % | NA | not evaluable | | non important | - |
Hypothyroidism TRAE (grade 3-4) | 1.02 [0.08, 13.37] | | < 1 | | 0% | 2 studies (2/-) | 49.3 % | some concern | not evaluable | moderate | non important | - |
Increase AST TRAE (grade 3-4) | 0.46 [0.03, 7.42] | | < 1 | | 0% | 1 study (1/-) | 70.6 % | NA | not evaluable | | non important | - |
Increased ALT TRAE (grade 3-4) | 1.17 [0.15, 9.26] | | < 1 | | 0% | 2 studies (2/-) | 44.1 % | some concern | not evaluable | moderate | non important | - |
Increased lipase level TRAE (grade 3-4) | 3.74 [0.42, 33.65] | | < 1 | | 0% | 1 study (1/-) | 12.1 % | NA | not evaluable | | non important | - |
Infusion-related reactions TRAE (grade 3-4) | 2.85 [0.32, 25.34] | | < 1 | | 17% | 2 studies (2/-) | 17.6 % | some concern | not evaluable | moderate | non important | - |
Leucopenia TRAE (grade 3-4) | 0.03 [0.01, 0.16] | | < 1 | | 0% | 2 studies (2/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
Maculopapular rash TRAE (grade 3-4) | 0.46 [0.01, 23.40] | | < 1 | | 0% | 1 study (1/-) | 64.7 % | NA | not evaluable | | non important | - |
Mucosal inflammation TRAE (grade 3-4) | 0.11 [0.01, 2.18] | | < 1 | | 0% | 1 study (1/-) | 92.3 % | NA | not evaluable | | non important | - |
Myalgia TRAE (grade 3-4) | 0.15 [0.01, 3.08] | | < 1 | | 0% | 1 study (1/-) | 88.7 % | NA | not evaluable | | non important | - |
Myocarditis TRAE (grade 3-4) | 0.93 [0.02, 46.93] | | < 1 | | 0% | 1 study (1/-) | 51.4 % | NA | not evaluable | | non important | - |
Nausea TRAE (grade 3-4) | 0.15 [0.01, 3.08] | | < 1 | | 0% | 1 study (1/-) | 88.7 % | NA | not evaluable | | non important | - |
Neutropenia TRAE (grade 3-4) | 0.03 [0.01, 0.09] | | < 1 | | 0% | 2 studies (2/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
Palmar-plantar erythrodysaesthesia syndrome TRAE (grade 3-4) | 0.46 [0.02, 13.86] | | < 1 | | 0% | 1 study (1/-) | 66.9 % | NA | not evaluable | | non important | - |
Peripheral neuropathy TRAE (grade 3-4) | 0.15 [0.01, 3.08] | | < 1 | | 0% | 1 study (1/-) | 88.7 % | NA | not evaluable | | non important | - |
Peripheral oedema TRAE (grade 3-4) | 0.15 [0.01, 3.08] | | < 1 | | 0% | 1 study (1/-) | 88.7 % | NA | not evaluable | | non important | - |
Peripheral sensory neuropathy TRAE (grade 3-4) | 0.46 [0.02, 13.86] | | < 1 | | 0% | 1 study (1/-) | 66.9 % | NA | not evaluable | | non important | - |
Pneumonia TRAE (grade 3-4) | 0.09 [0.00, 1.68] | | < 1 | | 0% | 1 study (1/-) | 94.4 % | NA | not evaluable | | non important | - |
Pneumonitis TRAE (grade 3-4) | 3.12 [0.52, 18.80] | | < 1 | | 0% | 2 studies (2/-) | 10.8 % | some concern | not evaluable | moderate | non important | - |
Pruritus generalised TRAE (grade 3-4) | 0.46 [0.01, 23.40] | | < 1 | | 0% | 1 study (1/-) | 64.7 % | NA | not evaluable | | non important | - |
Pruritus TRAE (grade 3-4) | 0.46 [0.01, 23.40] | | < 1 | | 0% | 1 study (1/-) | 64.7 % | NA | not evaluable | | non important | - |
Pyrexia TRAE (grade 3-4) | 0.93 [0.02, 46.93] | | < 1 | | 0% | 1 study (1/-) | 51.4 % | NA | not evaluable | | non important | - |
Rash TRAE (grade 3-4) | 2.79 [0.14, 56.11] | | < 1 | | 0% | 1 study (1/-) | 25.4 % | NA | not evaluable | | non important | - |
Renal and urinary disorders TRAE (grade 3-4) | 0.46 [0.01, 23.40] | | < 1 | | 0% | 1 study (1/-) | 64.7 % | NA | not evaluable | | non important | - |
Respiratory, thoracic and mediastinal disorders TRAE (grade 3-4) | 6.60 [0.37, 116.99] | | < 1 | | 0% | 1 study (1/-) | 10.2 % | NA | not evaluable | | non important | - |
Sepsis TRAE (grade 3-4) | 0.23 [0.01, 5.14] | | < 1 | | 0% | 1 study (1/-) | 82.0 % | NA | not evaluable | | non important | - |
Skin and subcutaneous tissue disorders TRAE (grade 3-4) | 2.79 [0.14, 56.11] | | < 1 | | 0% | 1 study (1/-) | 25.4 % | NA | not evaluable | | non important | - |
Stomatitis TRAE (grade 3-4) | 0.15 [0.01, 3.08] | | < 1 | | 0% | 1 study (1/-) | 88.7 % | NA | not evaluable | | non important | - |
Thyroiditis TRAE (grade 3-4) | 0.46 [0.01, 23.40] | | < 1 | | 0% | 1 study (1/-) | 64.7 % | NA | not evaluable | | non important | - |
Vitiligo TRAE (grade 3-4) | 0.46 [0.01, 23.40] | | < 1 | | 0% | 1 study (1/-) | 64.7 % | NA | not evaluable | | non important | - |
Vomiting TRAE (grade 3-4) | 0.15 [0.01, 3.08] | | < 1 | | 0% | 1 study (1/-) | 88.7 % | NA | not evaluable | | non important | - |
Weight decreased TRAE (grade 3-4) | 0.93 [0.06, 14.90] | | < 1 | | 0% | 1 study (1/-) | 52.1 % | NA | not evaluable | | non important | - |
AE (grade 3-4) endpoints 00 |
Alopecia AE (grade 3-4) | 0.47 [0.02, 14.16] | | < 1 | | 0% | 1 study (1/-) | 66.4 % | NA | not evaluable | | non important | - |
Anaemia AE (grade 3-4) | 0.39 [0.21, 0.73] | | < 1 | | 0% | 1 study (1/-) | 99.8 % | NA | not evaluable | | non important | - |
Arthralgia AE (grade 3-4) | 2.86 [0.30, 27.54] | | < 1 | | 0% | 1 study (1/-) | 18.4 % | NA | not evaluable | | non important | - |
Asthenia AE (grade 3-4) | 0.58 [0.24, 1.41] | | < 1 | | 0% | 1 study (1/-) | 88.6 % | NA | not evaluable | | non important | - |
Back pain AE (grade 3-4) | 1.67 [0.49, 5.73] | | < 1 | | 0% | 1 study (1/-) | 20.8 % | NA | not evaluable | | non important | - |
Constipation AE (grade 3-4) | 1.90 [0.17, 21.02] | | < 1 | | 0% | 1 study (1/-) | 30.2 % | NA | not evaluable | | non important | - |
Cough AE (grade 3-4) | 1.90 [0.17, 21.02] | | < 1 | | 0% | 1 study (1/-) | 30.2 % | NA | not evaluable | | non important | - |
Decreased appetite AE (grade 3-4) | 0.21 [0.04, 0.97] | | < 1 | | 0% | 1 study (1/-) | 97.7 % | NA | not evaluable | | non important | - |
Diarrhoea AE (grade 3-4) | 0.34 [0.11, 1.08] | | < 1 | | 0% | 1 study (1/-) | 96.6 % | NA | not evaluable | | non important | - |
Dysgeusia AE (grade 3-4) | 0.95 [0.02, 47.91] | | < 1 | | 0% | 1 study (1/-) | 51.0 % | NA | not evaluable | | non important | - |
Dyspnoea AE (grade 3-4) | 1.02 [0.49, 2.13] | | < 1 | | 0% | 1 study (1/-) | 48.2 % | NA | not evaluable | | non important | - |
Fatigue AE (grade 3-4) | 0.69 [0.37, 1.31] | | < 1 | | 0% | 1 study (1/-) | 87.0 % | NA | not evaluable | | non important | - |
Febrile neutropenia AE (grade 3-4) | 0.01 [0.00, 0.10] | | < 1 | | 0% | 1 study (1/-) | 100.0 % | NA | not evaluable | | non important | - |
Myalgia AE (grade 3-4) | 0.24 [0.03, 2.12] | | < 1 | | 0% | 1 study (1/-) | 90.0 % | NA | not evaluable | | non important | - |
Nausea AE (grade 3-4) | 1.90 [0.35, 10.44] | | < 1 | | 0% | 1 study (1/-) | 23.0 % | NA | not evaluable | | non important | - |
Neutropenia AE (grade 3-4) | 0.03 [0.01, 0.11] | | < 1 | | 0% | 1 study (1/-) | 100.0 % | NA | not evaluable | | non important | - |
Peripheral neuropathy AE (grade 3-4) | 0.07 [0.00, 1.18] | | < 1 | | 0% | 1 study (1/-) | 96.6 % | NA | not evaluable | | non important | - |
Peripheral oedema AE (grade 3-4) | 0.32 [0.03, 3.04] | | < 1 | | 0% | 1 study (1/-) | 83.9 % | NA | not evaluable | | non important | - |
Pyrexia AE (grade 3-4) | 0.95 [0.06, 15.21] | | < 1 | | 0% | 1 study (1/-) | 51.5 % | NA | not evaluable | | non important | - |
Stomatitis AE (grade 3-4) | 0.08 [0.01, 0.66] | | < 1 | | 0% | 1 study (1/-) | 99.1 % | NA | not evaluable | | non important | - |
Vomiting AE (grade 3-4) | 0.47 [0.09, 2.59] | | < 1 | | 0% | 1 study (1/-) | 80.5 % | NA | not evaluable | | non important | - |