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) | 0.70 [0.61, 0.80] | | < 1 | | 57% | 12 studies (12/-) | 100.0 % | low | low | high | crucial | - |
deaths (OS) (extension) | 0.65 [0.54, 0.78] | | < 1 | | 69% | 5 studies (5/-) | 100.0 % | low | not evaluable | high | important | - |
MFS | 0.64 [0.47, 0.87] | | < 1 | | 48% | 2 studies (2/-) | 99.8 % | low | not evaluable | high | important | - |
PFS (extension) | 0.58 [0.48, 0.70] | | < 1 | | 77% | 5 studies (5/-) | 100.0 % | low | not evaluable | high | important | - |
progression or deaths (PFS) | 0.61 [0.52, 0.72] | | < 1 | | 79% | 11 studies (11/-) | 100.0 % | low | low | high | important | - |
RFS (extension) | 0.63 [0.50, 0.80] | | < 1 | | 69% | 2 studies (2/-) | 100.0 % | low | not evaluable | high | important | - |
RFS/DFS | 0.59 [0.50, 0.70] | | < 1 | | 0% | 4 studies (4/-) | 100.0 % | low | not evaluable | high | important | - |
DCR | 0.91 [0.63, 1.32] | | > 1 | | 0% | 1 study (1/-) | 31.6 % | NA | not evaluable | | non important | - |
DMFS | 0.60 [0.49, 0.73] | | < 1 | | 0% | 1 study (1/-) | 100.0 % | NA | not evaluable | | non important | - |
DOR | 0.41 [0.20, 0.83] | | < 1 | | 0% | 1 study (1/-) | 99.3 % | NA | not evaluable | | non important | - |
DOR (extension) | 3.45 [1.46, 8.18] | | > 1 | | 0% | 1 study (1/-) | 99.8 % | NA | not evaluable | | non important | - |
objective responses (ORR) | 2.58 [1.68, 3.97] | | > 1 | | 89% | 11 studies (11/-) | 100.0 % | low | low | high | non important | - |
objective responses (ORR) (extension) | 4.57 [3.31, 6.32] | | > 1 | | 50% | 3 studies (3/-) | 100.0 % | low | not evaluable | high | non important | - |
safety endpoints 00 |
AE (any grade) | 1.49 [0.61, 3.64] | | < 1 | | 76% | 5 studies (5/-) | 18.9 % | low | not evaluable | high | non important | - |
AE (grade 3-4) | 1.34 [0.47, 3.82] | | < 1 | | 97% | 5 studies (5/-) | 29.0 % | low | not evaluable | high | non important | - |
AE leading to death (grade 5) | 1.34 [0.65, 2.76] | | < 1 | | 0% | 6 studies (6/-) | 21.2 % | low | not evaluable | high | non important | - |
AE leading to treatment discontinuation (any grade) | 1.28 [0.36, 4.56] | | < 1 | | 95% | 6 studies (6/-) | 35.3 % | low | serious | high | non important | - |
AE leading to treatment discontinuation (grade 3-4) | 1.26 [0.15, 10.80] | | < 1 | | 96% | 4 studies (4/-) | 41.7 % | low | not evaluable | high | non important | - |
SAE (any grade) | 1.45 [0.55, 3.84] | | < 1 | | 85% | 3 studies (3/-) | 22.7 % | low | not evaluable | high | non important | - |
SAE (grade 3-4) | 1.77 [0.60, 5.28] | | < 1 | | 85% | 3 studies (3/-) | 15.2 % | low | not evaluable | high | non important | - |
STRAE (any grade) | 1.36 [0.75, 2.47] | | < 1 | | 82% | 6 studies (6/-) | 15.2 % | low | not evaluable | high | non important | - |
STRAE (grade 3-4) | 2.45 [0.78, 7.74] | | < 1 | | 55% | 5 studies (5/-) | 6.3 % | low | not evaluable | high | non important | - |
TRAE (any grade) | 1.21 [0.81, 1.80] | | < 1 | | 85% | 13 studies (13/-) | 17.8 % | low | low | high | non important | - |
TRAE (grade 3-4) | 1.32 [0.70, 2.51] | | < 1 | | 96% | 13 studies (13/-) | 19.4 % | low | low | high | non important | - |
TRAE leading to death (grade 5) | 1.09 [0.37, 3.25] | | < 1 | | 0% | 11 studies (11/-) | 43.9 % | low | low | high | non important | - |
TRAE leading to discontinuation (any grade) | 1.50 [0.57, 3.95] | | < 1 | | 96% | 10 studies (10/-) | 20.4 % | low | low | high | non important | - |
TRAE leading to discontinuation (grade 3-4) | 1.60 [0.40, 6.41] | | < 1 | | 95% | 9 studies (9/-) | 25.5 % | low | not evaluable | high | non important | - |
TRAE (grade 3-4) endpoints 00 |
Abdominal pain TRAE (grade 3-4) | 0.77 [0.21, 2.78] | | < 1 | | 0% | 8 studies (8/-) | 65.7 % | low | not evaluable | high | non important | - |
Acute kidney injury TRAE (grade 3-4) | 1.45 [0.11, 19.13] | | < 1 | | 0% | 2 studies (2/-) | 39.0 % | low | not evaluable | high | non important | - |
Adrenal insufficiency TRAE (grade 3-4) | 1.45 [0.57, 3.70] | | < 1 | | 0% | 6 studies (6/-) | 21.9 % | low | not evaluable | high | non important | - |
Alopecia TRAE (grade 3-4) | 0.95 [0.22, 4.21] | | < 1 | | 0% | 7 studies (7/-) | 52.5 % | some concern | not evaluable | moderate | non important | - |
Anaemia TRAE (grade 3-4) | 0.39 [0.12, 1.24] | | < 1 | | 8% | 7 studies (7/-) | 94.5 % | some concern | not evaluable | moderate | non important | - |
Arthralgia TRAE (grade 3-4) | 1.30 [0.64, 2.62] | | < 1 | | 0% | 12 studies (12/-) | 23.4 % | low | low | high | non important | - |
Asthenia TRAE (grade 3-4) | 0.73 [0.32, 1.67] | | < 1 | | 0% | 9 studies (9/-) | 77.0 % | low | not evaluable | high | non important | - |
Blood and lymphatic system disorders TRAE (grade 3-4) | 3.02 [0.28, 33.13] | | < 1 | | 0% | 2 studies (2/-) | 18.5 % | low | not evaluable | high | non important | - |
Blood creatinine increased TRAE (grade 3-4) | 0.72 [0.06, 9.49] | | < 1 | | 0% | 2 studies (2/-) | 59.7 % | low | not evaluable | high | non important | - |
Chills TRAE (grade 3-4) | 0.94 [0.13, 6.73] | | < 1 | | 0% | 4 studies (4/-) | 52.4 % | some concern | not evaluable | moderate | non important | - |
Chorioretinopathy TRAE (grade 3-4) | 0.61 [0.02, 18.27] | | < 1 | | 0% | 1 study (1/-) | 61.1 % | NA | not evaluable | | non important | - |
Colitis TRAE (grade 3-4) | 1.09 [0.30, 3.99] | | < 1 | | 82% | 9 studies (9/-) | 44.6 % | low | not evaluable | high | non important | - |
Constipation TRAE (grade 3-4) | 0.95 [0.16, 5.50] | | < 1 | | 0% | 5 studies (5/-) | 52.2 % | some concern | not evaluable | moderate | non important | - |
Cough TRAE (grade 3-4) | 0.97 [0.25, 3.82] | | < 1 | | 0% | 7 studies (7/-) | 51.8 % | low | not evaluable | high | non important | - |
Decreased appetite TRAE (grade 3-4) | 1.05 [0.33, 3.30] | | < 1 | | 0% | 10 studies (10/-) | 46.8 % | low | low | high | non important | - |
Diabetes TRAE (grade 3-4) | 2.27 [0.52, 9.86] | | < 1 | | 0% | 5 studies (5/-) | 13.8 % | low | serious | high | non important | - |
Diarrhoea TRAE (grade 3-4) | 0.76 [0.35, 1.62] | | < 1 | | 69% | 12 studies (12/-) | 76.4 % | low | low | high | non important | - |
Dizziness TRAE (grade 3-4) | 0.96 [0.06, 15.59] | | < 1 | | 0% | 2 studies (2/-) | 51.1 % | low | not evaluable | high | non important | - |
Dry skin TRAE (grade 3-4) | 1.23 [0.37, 4.12] | | < 1 | | 0% | 10 studies (10/-) | 36.7 % | low | critical | high | non important | - |
Dysgeusia TRAE (grade 3-4) | 0.96 [0.06, 15.59] | | < 1 | | 0% | 2 studies (2/-) | 51.1 % | low | not evaluable | high | non important | - |
Dyspepsia TRAE (grade 3-4) | 0.96 [0.06, 15.59] | | < 1 | | 0% | 2 studies (2/-) | 51.1 % | low | not evaluable | high | non important | - |
Dyspnoea TRAE (grade 3-4) | 1.42 [0.43, 4.65] | | < 1 | | 0% | 7 studies (7/-) | 28.1 % | low | not evaluable | high | non important | - |
Endocrine disorders TRAE (grade 3-4) | 6.23 [1.33, 29.21] | | < 1 | | 0% | 3 studies (3/-) | 1.0 % | low | not evaluable | high | non important | - |
Erythema TRAE (grade 3-4) | 7.41 [0.37, 148.78] | | < 1 | | 0% | 1 study (1/-) | 9.8 % | NA | not evaluable | | non important | - |
Eye disorders TRAE (grade 3-4) | 1.45 [0.11, 19.13] | | < 1 | | 0% | 2 studies (2/-) | 39.0 % | low | not evaluable | high | non important | - |
Fatigue TRAE (grade 3-4) | 0.76 [0.37, 1.58] | | < 1 | | 35% | 11 studies (11/-) | 77.0 % | low | low | high | non important | - |
Gastritis TRAE (grade 3-4) | 2.32 [0.20, 26.84] | | < 1 | | 0% | 2 studies (2/-) | 25.1 % | low | not evaluable | high | non important | - |
Gastrointestinal disorders TRAE (grade 3-4) | 1.57 [0.10, 24.07] | | < 1 | | 91% | 4 studies (4/-) | 37.4 % | low | not evaluable | high | non important | - |
General disorders and administration site conditions TRAE (grade 3-4) | 2.32 [0.20, 26.84] | | < 1 | | 0% | 2 studies (2/-) | 25.1 % | low | not evaluable | high | non important | - |
Headache TRAE (grade 3-4) | 0.60 [0.19, 1.92] | | < 1 | | 0% | 8 studies (8/-) | 80.4 % | low | serious | high | non important | - |
Hepatitis TRAE (grade 3-4) | 3.83 [1.67, 8.76] | | < 1 | | 0% | 9 studies (9/-) | 0.1 % | low | not evaluable | high | non important | - |
Hepatobiliary disorders TRAE (grade 3-4) | 1.42 [0.07, 29.90] | | < 1 | | 91% | 3 studies (3/-) | 41.2 % | low | not evaluable | high | non important | - |
Hypersensitivity TRAE (grade 3-4) | 1.49 [0.11, 19.39] | | < 1 | | 0% | 2 studies (2/-) | 38.2 % | low | not evaluable | high | non important | - |
Hypertension TRAE (grade 3-4) | 0.96 [0.06, 15.59] | | < 1 | | 0% | 2 studies (2/-) | 51.1 % | low | not evaluable | high | non important | - |
Hyperthyroidism TRAE (grade 3-4) | 1.67 [0.63, 4.40] | | < 1 | | 0% | 12 studies (12/-) | 15.1 % | low | low | high | non important | - |
Hypophysitis TRAE (grade 3-4) | 0.67 [0.27, 1.64] | | < 1 | | 17% | 10 studies (10/-) | 81.1 % | low | low | high | non important | - |
Hypothyroidism TRAE (grade 3-4) | 0.97 [0.33, 2.85] | | < 1 | | 0% | 11 studies (11/-) | 52.0 % | low | low | high | non important | - |
Increase AST TRAE (grade 3-4) | 1.14 [0.33, 3.90] | | < 1 | | 69% | 8 studies (8/-) | 41.9 % | low | not evaluable | high | non important | - |
Increased ALT TRAE (grade 3-4) | 1.32 [0.37, 4.69] | | < 1 | | 79% | 8 studies (8/-) | 33.6 % | low | not evaluable | high | non important | - |
Increased lipase level TRAE (grade 3-4) | 1.47 [0.89, 2.43] | | < 1 | | 48% | 5 studies (5/-) | 6.7 % | low | not evaluable | high | non important | - |
Infusion-related reactions TRAE (grade 3-4) | 0.97 [0.10, 9.43] | | < 1 | | 0% | 3 studies (3/-) | 50.9 % | low | not evaluable | high | non important | - |
Leucopenia TRAE (grade 3-4) | 0.16 [0.04, 0.65] | | < 1 | | 0% | 5 studies (5/-) | 99.4 % | low | serious | high | non important | - |
Maculopapular rash TRAE (grade 3-4) | 1.34 [0.84, 2.14] | | < 1 | | 0% | 11 studies (11/-) | 11.1 % | low | low | high | non important | - |
Metabolism and nutrition disorders TRAE (grade 3-4) | 1.29 [0.15, 11.24] | | < 1 | | 0% | 2 studies (2/-) | 40.9 % | low | not evaluable | high | non important | - |
Musculoskeletal and connective tissue disorders TRAE (grade 3-4) | 0.96 [0.03, 31.61] | | < 1 | | 63% | 2 studies (2/-) | 50.8 % | low | not evaluable | high | non important | - |
Myalgia TRAE (grade 3-4) | 1.18 [0.45, 3.05] | | < 1 | | 0% | 10 studies (10/-) | 36.9 % | low | critical | high | non important | - |
Myocarditis TRAE (grade 3-4) | 1.97 [0.07, 58.99] | | < 1 | | 0% | 1 study (1/-) | 34.9 % | NA | not evaluable | | non important | - |
Myositis TRAE (grade 3-4) | 0.95 [0.16, 5.51] | | < 1 | | 0% | 5 studies (5/-) | 52.2 % | low | not evaluable | high | non important | - |
Nausea TRAE (grade 3-4) | 0.56 [0.23, 1.37] | | < 1 | | 0% | 12 studies (12/-) | 89.8 % | low | low | high | non important | - |
Nephritis TRAE (grade 3-4) | 1.03 [0.15, 6.90] | | < 1 | | 0% | 3 studies (3/-) | 48.7 % | some concern | not evaluable | moderate | non important | - |
Nervous system disorders TRAE (grade 3-4) | 1.07 [0.16, 7.27] | | < 1 | | 0% | 2 studies (2/-) | 47.3 % | low | not evaluable | high | non important | - |
Neutropenia TRAE (grade 3-4) | 0.20 [0.06, 0.72] | | < 1 | | 0% | 7 studies (7/-) | 99.3 % | some concern | serious | moderate | non important | - |
Palmar-plantar erythrodysaesthesia syndrome TRAE (grade 3-4) | 0.96 [0.06, 15.59] | | < 1 | | 0% | 2 studies (2/-) | 51.1 % | low | not evaluable | high | non important | - |
Pancreatitis TRAE (grade 3-4) | 1.12 [0.24, 5.34] | | < 1 | | 0% | 5 studies (5/-) | 44.3 % | low | not evaluable | high | non important | - |
Pancytopenia TRAE (grade 3-4) | 0.16 [0.01, 3.29] | | < 1 | | 0% | 1 study (1/-) | 87.9 % | NA | not evaluable | | non important | - |
Paraesthesia TRAE (grade 3-4) | 0.75 [0.18, 3.09] | | < 1 | | 0% | 7 studies (7/-) | 65.6 % | some concern | serious | moderate | non important | - |
Peripheral neuropathy TRAE (grade 3-4) | 0.51 [0.10, 2.70] | | < 1 | | 0% | 4 studies (4/-) | 78.6 % | some concern | not evaluable | moderate | non important | - |
Peripheral oedema TRAE (grade 3-4) | 1.22 [0.02, 61.84] | | < 1 | | 0% | 1 study (1/-) | 46.1 % | NA | not evaluable | | non important | - |
Pneumonitis TRAE (grade 3-4) | 2.07 [0.79, 5.39] | | < 1 | | 0% | 10 studies (10/-) | 6.9 % | low | low | high | non important | - |
Pruritic rash TRAE (grade 3-4) | 0.96 [0.13, 6.82] | | < 1 | | 0% | 4 studies (4/-) | 51.7 % | low | not evaluable | high | non important | - |
Pruritus TRAE (grade 3-4) | 1.31 [0.52, 3.29] | | < 1 | | 0% | 12 studies (12/-) | 28.2 % | low | low | high | non important | - |
Pyrexia TRAE (grade 3-4) | 1.09 [0.41, 2.86] | | < 1 | | 0% | 9 studies (9/-) | 43.4 % | low | not evaluable | high | non important | - |
Rash TRAE (grade 3-4) | 0.86 [0.44, 1.66] | | < 1 | | 18% | 10 studies (10/-) | 67.6 % | low | low | high | non important | - |
Renal and urinary disorders TRAE (grade 3-4) | 1.00 [0.02, 50.62] | | < 1 | | 0% | 1 study (1/-) | 50.0 % | NA | not evaluable | | non important | - |
Respiratory, thoracic and mediastinal disorders TRAE (grade 3-4) | 0.98 [0.15, 6.59] | | < 1 | | 22% | 4 studies (4/-) | 50.8 % | low | not evaluable | high | non important | - |
Sarcoidosis TRAE (grade 3-4) | 0.97 [0.10, 9.40] | | < 1 | | 0% | 3 studies (3/-) | 51.0 % | low | not evaluable | high | non important | - |
Severe skin reaction TRAE (grade 3-4) | 5.95 [0.30, 119.02] | | < 1 | | 0% | 1 study (1/-) | 12.5 % | NA | not evaluable | | non important | - |
Skin and subcutaneous tissue disorders TRAE (grade 3-4) | 0.85 [0.14, 5.17] | | < 1 | | 59% | 4 studies (4/-) | 57.0 % | low | not evaluable | high | non important | - |
Stomatitis TRAE (grade 3-4) | 0.96 [0.06, 15.59] | | < 1 | | 0% | 2 studies (2/-) | 51.1 % | low | not evaluable | high | non important | - |
Thrombocytopenia TRAE (grade 3-4) | 0.23 [0.06, 0.85] | | < 1 | | 0% | 5 studies (5/-) | 98.6 % | some concern | not evaluable | moderate | non important | - |
Thyroiditis TRAE (grade 3-4) | 1.17 [0.21, 6.41] | | < 1 | | 0% | 5 studies (5/-) | 42.9 % | low | serious | high | non important | - |