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 [0.74, 0.86] | | < 1 | | 59% | 20 studies (20/-) | 100.0 % | some concern | critical | moderate | crucial | - |
deaths (OS) (extension) | 0.68 [0.60, 0.78] | | < 1 | | 50% | 6 studies (6/-) | 100.0 % | some concern | not evaluable | moderate | important | - |
PFS (extension) | 0.65 [0.48, 0.86] | | < 1 | | 92% | 6 studies (6/-) | 99.9 % | some concern | not evaluable | moderate | important | - |
progression or deaths (PFS) | 0.70 [0.62, 0.78] | | < 1 | | 85% | 21 studies (21/-) | 100.0 % | some concern | critical | moderate | important | - |
DOR | 2.27 [1.44, 3.57] | | < 1 | | 0% | 2 studies (2/-) | 0.0 % | some concern | not evaluable | moderate | non important | - |
objective responses (ORR) | 1.61 [1.34, 1.94] | | > 1 | | 82% | 20 studies (20/-) | 100.0 % | some concern | low | moderate | non important | - |
objective responses (ORR) (extension) | 2.00 [1.13, 3.54] | | > 1 | | 88% | 5 studies (5/-) | 99.2 % | some concern | not evaluable | moderate | non important | - |
safety endpoints 00 |
AE (any grade) | 0.72 [0.39, 1.35] | | < 1 | | 76% | 10 studies (10/-) | 84.7 % | some concern | critical | moderate | non important | - |
AE (grade 3-4) | 0.85 [0.59, 1.22] | | < 1 | | 91% | 10 studies (10/-) | 81.1 % | some concern | low | moderate | non important | - |
AE leading to death (grade 5) | 1.18 [0.86, 1.63] | | < 1 | | 48% | 10 studies (10/-) | 15.7 % | some concern | critical | moderate | non important | - |
AE leading to treatment discontinuation (any grade) | 1.27 [0.91, 1.75] | | < 1 | | 81% | 10 studies (10/-) | 7.9 % | some concern | low | moderate | non important | - |
AE leading to treatment discontinuation (grade 3-4) | 1.58 [1.08, 2.31] | | < 1 | | 56% | 5 studies (5/-) | 0.9 % | low | not evaluable | high | non important | - |
SAE (any grade) | 1.48 [1.12, 1.95] | | < 1 | | 69% | 5 studies (5/-) | 0.3 % | some concern | not evaluable | moderate | non important | - |
STRAE (any grade) | 1.45 [1.10, 1.91] | | < 1 | | 79% | 13 studies (13/-) | 0.4 % | some concern | low | moderate | non important | - |
STRAE (grade 3-4) | 1.43 [0.99, 2.06] | | < 1 | | 76% | 9 studies (9/-) | 2.8 % | some concern | not evaluable | moderate | non important | - |
TRAE (any grade) | 0.64 [0.39, 1.03] | | < 1 | | 93% | 14 studies (14/-) | 96.6 % | some concern | critical | moderate | non important | - |
TRAE (grade 3-4) | 0.75 [0.48, 1.16] | | < 1 | | 95% | 14 studies (14/-) | 90.2 % | some concern | low | moderate | non important | - |
TRAE leading to death (grade 5) | 1.18 [0.82, 1.69] | | < 1 | | 0% | 13 studies (13/-) | 19.2 % | some concern | low | moderate | non important | - |
TRAE leading to discontinuation (any grade) | 1.27 [0.81, 1.98] | | < 1 | | 84% | 10 studies (10/-) | 14.7 % | some concern | low | moderate | non important | - |
TRAE leading to discontinuation (grade 3-4) | 1.87 [1.21, 2.88] | | < 1 | | 73% | 10 studies (10/-) | 0.3 % | some concern | low | moderate | non important | - |
TRAE (grade 3-4) endpoints 00 |
Acute kidney injury TRAE (grade 3-4) | 4.32 [0.19, 97.73] | | < 1 | | 0% | 1 study (1/-) | 18.2 % | NA | not evaluable | | non important | - |
Adrenal insufficiency TRAE (grade 3-4) | 2.19 [0.70, 6.89] | | < 1 | | 0% | 7 studies (7/-) | 9.0 % | some concern | not evaluable | moderate | non important | - |
Alopecia TRAE (grade 3-4) | 0.52 [0.14, 1.94] | | < 1 | | 0% | 8 studies (8/-) | 83.4 % | some concern | serious | moderate | non important | - |
Anaemia TRAE (grade 3-4) | 0.27 [0.14, 0.53] | | < 1 | | 90% | 13 studies (13/-) | 100.0 % | some concern | critical | moderate | non important | - |
Arthralgia TRAE (grade 3-4) | 0.80 [0.21, 2.99] | | < 1 | | 0% | 3 studies (3/-) | 63.1 % | some concern | not evaluable | moderate | non important | - |
Asthenia TRAE (grade 3-4) | 0.55 [0.33, 0.91] | | < 1 | | 18% | 11 studies (11/-) | 99.0 % | some concern | low | moderate | non important | - |
Blood creatinine increased TRAE (grade 3-4) | 1.00 [0.13, 7.77] | | < 1 | | 0% | 3 studies (3/-) | 50.1 % | some concern | not evaluable | moderate | non important | - |
Colitis TRAE (grade 3-4) | 3.89 [1.67, 9.06] | | < 1 | | 0% | 10 studies (10/-) | 0.1 % | some concern | low | moderate | non important | - |
Constipation TRAE (grade 3-4) | 0.68 [0.25, 1.86] | | < 1 | | 0% | 13 studies (13/-) | 77.2 % | some concern | critical | moderate | non important | - |
Decreased appetite TRAE (grade 3-4) | 0.94 [0.58, 1.54] | | < 1 | | 19% | 13 studies (13/-) | 59.0 % | some concern | low | moderate | non important | - |
Diabetes TRAE (grade 3-4) | 1.86 [0.45, 7.64] | | < 1 | | 0% | 6 studies (6/-) | 19.5 % | some concern | serious | moderate | non important | - |
Diarrhoea TRAE (grade 3-4) | 1.77 [1.17, 2.68] | | < 1 | | 8% | 15 studies (15/-) | 0.3 % | some concern | low | moderate | non important | - |
Dizziness TRAE (grade 3-4) | 1.05 [0.02, 53.86] | | < 1 | | 0% | 1 study (1/-) | 49.0 % | NA | not evaluable | | non important | - |
Dysgeusia TRAE (grade 3-4) | 0.84 [0.12, 5.97] | | < 1 | | 0% | 4 studies (4/-) | 57.0 % | some concern | not evaluable | moderate | non important | - |
Epistaxis TRAE (grade 3-4) | 8.09 [0.43, 153.59] | | < 1 | | 0% | 1 study (1/-) | 8.4 % | NA | not evaluable | | non important | - |
Fatigue TRAE (grade 3-4) | 1.03 [0.67, 1.58] | | < 1 | | 40% | 13 studies (13/-) | 44.6 % | some concern | low | moderate | non important | - |
Febrile neutropenia TRAE (grade 3-4) | 1.65 [1.10, 2.48] | | < 1 | | 0% | 4 studies (4/-) | 0.8 % | some concern | not evaluable | moderate | non important | - |
Gastrointestinal disorders TRAE (grade 3-4) | 1.19 [0.36, 3.94] | | < 1 | | 0% | 1 study (1/-) | 39.0 % | NA | not evaluable | | non important | - |
Guillain-Barré syndrome TRAE (grade 3-4) | 1.00 [0.02, 50.55] | | < 1 | | 0% | 1 study (1/-) | 50.0 % | NA | not evaluable | | non important | - |
Hepatitis TRAE (grade 3-4) | 5.50 [2.04, 14.84] | | < 1 | | 0% | 8 studies (8/-) | 0.0 % | some concern | not evaluable | moderate | non important | - |
Hypertension TRAE (grade 3-4) | 1.00 [0.57, 1.78] | | < 1 | | 0% | 1 study (1/-) | 49.6 % | NA | not evaluable | | non important | - |
Hyperthyroidism TRAE (grade 3-4) | 1.18 [0.39, 3.61] | | < 1 | | 0% | 11 studies (11/-) | 38.6 % | some concern | critical | moderate | non important | - |
Hypophysitis TRAE (grade 3-4) | 1.90 [0.46, 7.81] | | < 1 | | 0% | 6 studies (6/-) | 18.7 % | some concern | serious | moderate | non important | - |
Hypothyroidism TRAE (grade 3-4) | 1.82 [0.71, 4.66] | | < 1 | | 0% | 14 studies (14/-) | 10.5 % | some concern | critical | moderate | non important | - |
Increase AST TRAE (grade 3-4) | 2.07 [0.70, 6.13] | | < 1 | | 0% | 5 studies (5/-) | 9.4 % | some concern | not evaluable | moderate | non important | - |
Increased ALT TRAE (grade 3-4) | 2.16 [1.08, 4.32] | | < 1 | | 0% | 7 studies (7/-) | 1.5 % | some concern | not evaluable | moderate | non important | - |
Increased lacrimation (TRAE grade 3-4) | 1.05 [0.02, 53.86] | | < 1 | | 0% | 1 study (1/-) | 49.0 % | NA | not evaluable | | non important | - |
Increased lipase level TRAE (grade 3-4) | 7.55 [2.24, 25.47] | | < 1 | | 0% | 1 study (1/-) | 0.1 % | NA | not evaluable | | non important | - |
Infusion-related reactions TRAE (grade 3-4) | 0.55 [0.15, 2.03] | | < 1 | | 0% | 6 studies (6/-) | 81.4 % | some concern | serious | moderate | non important | - |
Leucopenia TRAE (grade 3-4) | 0.65 [0.18, 2.35] | | < 1 | | 61% | 5 studies (5/-) | 74.1 % | some concern | not evaluable | moderate | non important | - |
Maculopapular rash TRAE (grade 3-4) | 3.26 [0.66, 16.22] | | < 1 | | 0% | 3 studies (3/-) | 7.5 % | some concern | not evaluable | moderate | non important | - |
Mucosal inflammation TRAE (grade 3-4) | 0.98 [0.02, 49.83] | | < 1 | | 0% | 1 study (1/-) | 50.3 % | NA | not evaluable | | non important | - |
Myalgia TRAE (grade 3-4) | 1.73 [0.30, 10.01] | | < 1 | | 0% | 3 studies (3/-) | 27.1 % | some concern | not evaluable | moderate | non important | - |
Myocarditis TRAE (grade 3-4) | 1.94 [0.06, 57.80] | | < 1 | | 0% | 1 study (1/-) | 35.4 % | NA | not evaluable | | non important | - |
Myositis TRAE (grade 3-4) | 1.05 [0.16, 6.91] | | < 1 | | 0% | 4 studies (4/-) | 48.0 % | some concern | not evaluable | moderate | non important | - |
Nausea TRAE (grade 3-4) | 0.75 [0.39, 1.44] | | < 1 | | 44% | 13 studies (13/-) | 80.3 % | some concern | critical | moderate | non important | - |
Nephritis TRAE (grade 3-4) | 1.82 [0.52, 6.35] | | < 1 | | 0% | 8 studies (8/-) | 17.5 % | some concern | serious | moderate | non important | - |
Neutropenia TRAE (grade 3-4) | 0.32 [0.17, 0.61] | | < 1 | | 84% | 13 studies (13/-) | 100.0 % | some concern | critical | moderate | non important | - |
Pancreatitis TRAE (grade 3-4) | 2.11 [0.47, 9.43] | | < 1 | | 0% | 5 studies (5/-) | 16.5 % | some concern | serious | moderate | non important | - |
Pancytopenia TRAE (grade 3-4) | 0.52 [0.02, 15.84] | | < 1 | | 0% | 1 study (1/-) | 64.4 % | NA | not evaluable | | non important | - |
Paraesthesia TRAE (grade 3-4) | 0.50 [0.02, 14.97] | | < 1 | | 0% | 1 study (1/-) | 65.3 % | NA | not evaluable | | non important | - |
Peripheral neuropathy TRAE (grade 3-4) | 1.16 [0.56, 2.42] | | < 1 | | 0% | 5 studies (5/-) | 34.3 % | some concern | not evaluable | moderate | non important | - |
Peripheral oedema TRAE (grade 3-4) | 1.02 [0.06, 16.38] | | < 1 | | 0% | 2 studies (2/-) | 49.5 % | some concern | not evaluable | moderate | non important | - |
Peripheral sensory neuropathy TRAE (grade 3-4) | 0.64 [0.01, 29.61] | | < 1 | | 78% | 2 studies (2/-) | 58.9 % | some concern | not evaluable | moderate | non important | - |
Pneumonia TRAE (grade 3-4) | 2.12 [0.07, 64.42] | | < 1 | | 0% | 1 study (1/-) | 33.5 % | NA | not evaluable | | non important | - |
Pneumonitis TRAE (grade 3-4) | 2.56 [1.42, 4.62] | | < 1 | | 0% | 11 studies (11/-) | 0.1 % | some concern | low | moderate | non important | - |
Pruritus TRAE (grade 3-4) | 1.90 [0.64, 5.69] | | < 1 | | 0% | 10 studies (10/-) | 12.5 % | some concern | critical | moderate | non important | - |
Pyrexia TRAE (grade 3-4) | 0.66 [0.05, 8.61] | | < 1 | | 0% | 2 studies (2/-) | 62.4 % | some concern | not evaluable | moderate | non important | - |
Rash TRAE (grade 3-4) | 2.53 [1.31, 4.86] | | < 1 | | 0% | 14 studies (14/-) | 0.3 % | some concern | low | moderate | non important | - |
Renal and urinary disorders TRAE (grade 3-4) | 1.97 [0.07, 59.09] | | < 1 | | 0% | 1 study (1/-) | 35.0 % | NA | not evaluable | | non important | - |
Respiratory, thoracic and mediastinal disorders TRAE (grade 3-4) | 12.07 [0.67, 217.19] | | < 1 | | 0% | 1 study (1/-) | 4.7 % | NA | not evaluable | | non important | - |
Sepsis TRAE (grade 3-4) | 2.06 [0.19, 22.93] | | < 1 | | 0% | 2 studies (2/-) | 27.9 % | some concern | not evaluable | moderate | non important | - |
Severe skin reaction TRAE (grade 3-4) | 2.45 [0.73, 8.21] | | < 1 | | 30% | 5 studies (5/-) | 7.3 % | some concern | not evaluable | moderate | non important | - |
Skin and subcutaneous tissue disorders TRAE (grade 3-4) | 5.00 [0.58, 43.09] | | < 1 | | 0% | 1 study (1/-) | 7.3 % | NA | not evaluable | | non important | - |
Stomatitis TRAE (grade 3-4) | 1.04 [0.27, 4.02] | | < 1 | | 0% | 5 studies (5/-) | 47.6 % | some concern | not evaluable | moderate | non important | - |
Thrombocytopenia TRAE (grade 3-4) | 0.44 [0.21, 0.91] | | < 1 | | 73% | 10 studies (10/-) | 98.6 % | some concern | critical | moderate | non important | - |
Thyroiditis TRAE (grade 3-4) | 0.78 [0.08, 7.49] | | < 1 | | 0% | 3 studies (3/-) | 58.6 % | some concern | not evaluable | moderate | non important | - |
Vomiting TRAE (grade 3-4) | 0.63 [0.32, 1.23] | | < 1 | | 33% | 13 studies (13/-) | 91.2 % | some concern | critical | moderate | non important | - |
AE (grade 3-4) endpoints 00 |
hepatitis (Autoimmune) AE (grade 3-4) | 3.10 [0.49, 19.80] | | < 1 | | 0% | 3 studies (3/-) | 11.7 % | some concern | not evaluable | moderate | non important | - |
Abdominal pain AE (grade 3-4) | 1.23 [0.24, 6.38] | | < 1 | | 0% | 1 study (1/-) | 40.4 % | NA | not evaluable | | non important | - |
Acute kidney injury AE (grade 3-4) | 0.24 [0.01, 5.34] | | < 1 | | 0% | 1 study (1/-) | 81.4 % | NA | not evaluable | | non important | - |
Agranulocytosis (AE grade 3-4) | 0.24 [0.01, 7.31] | | < 1 | | 0% | 1 study (1/-) | 78.8 % | NA | not evaluable | | non important | - |
Alopecia AE (grade 3-4) | 0.43 [0.10, 1.79] | | < 1 | | 0% | 5 studies (5/-) | 87.6 % | some concern | not evaluable | moderate | non important | - |
Anaemia AE (grade 3-4) | 0.33 [0.15, 0.74] | | < 1 | | 92% | 8 studies (8/-) | 99.6 % | some concern | serious | moderate | non important | - |
Arthralgia AE (grade 3-4) | 2.12 [0.74, 6.09] | | < 1 | | 0% | 4 studies (4/-) | 8.2 % | low | not evaluable | high | non important | - |
Asthenia AE (grade 3-4) | 0.97 [0.66, 1.43] | | < 1 | | 0% | 8 studies (8/-) | 56.4 % | some concern | not evaluable | moderate | non important | - |
Back pain AE (grade 3-4) | 0.79 [0.29, 2.15] | | < 1 | | 0% | 5 studies (5/-) | 67.7 % | some concern | not evaluable | moderate | non important | - |
Blood creatinine increased AE (grade 3-4) | 1.04 [0.10, 10.25] | | < 1 | | 0% | 2 studies (2/-) | 48.8 % | some concern | not evaluable | moderate | non important | - |
Colitis AE (grade 3-4) | 2.18 [0.61, 7.72] | | < 1 | | 0% | 2 studies (2/-) | 11.5 % | low | not evaluable | high | non important | - |
Constipation AE (grade 3-4) | 1.30 [0.58, 2.88] | | < 1 | | 0% | 8 studies (8/-) | 26.1 % | some concern | not evaluable | moderate | non important | - |
Cough AE (grade 3-4) | 0.99 [0.33, 3.02] | | < 1 | | 0% | 7 studies (7/-) | 50.4 % | low | not evaluable | high | non important | - |
Decreased appetite AE (grade 3-4) | 1.41 [0.81, 2.43] | | < 1 | | 0% | 8 studies (8/-) | 11.1 % | some concern | serious | moderate | non important | - |