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) | 0.86 [0.80, 0.93] | | < 1 | | 35% | 9 studies (9/-) | 100.0 % | some concern | not evaluable | moderate | crucial | - |
deaths (OS) (extension) | 0.77 [0.70, 0.85] | | < 1 | | 0% | 3 studies (3/-) | 100.0 % | some concern | not evaluable | moderate | important | - |
PFS (extension) | 0.72 [0.41, 1.26] | | < 1 | | 95% | 2 studies (2/-) | 87.4 % | some concern | not evaluable | moderate | important | - |
progression or deaths (PFS) | 0.87 [0.71, 1.06] | | < 1 | | 84% | 7 studies (7/-) | 91.8 % | some concern | not evaluable | moderate | important | - |
RFS/DFS | 0.72 [0.59, 0.88] | | < 1 | | 0% | 1 study (1/-) | 99.9 % | NA | not evaluable | | important | - |
CRR | 1.96 [1.21, 3.17] | | > 1 | | 0% | 1 study (1/-) | 99.7 % | NA | not evaluable | | non important | - |
DCR | 1.85 [1.35, 2.54] | | > 1 | | 0% | 1 study (1/-) | 100.0 % | NA | not evaluable | | non important | - |
DMFS | 0.75 [0.59, 0.95] | | < 1 | | 0% | 1 study (1/-) | 99.2 % | NA | not evaluable | | non important | - |
DOR | 0.50 [0.20, 1.24] | | < 1 | | 91% | 5 studies (5/-) | 93.3 % | some concern | not evaluable | moderate | non important | - |
events or deaths (EFS) | 0.80 [0.63, 1.01] | | < 1 | | 57% | 2 studies (2/-) | 96.9 % | some concern | not evaluable | moderate | non important | - |
objective responses (ORR) | 0.99 [0.60, 1.62] | | > 1 | | 94% | 8 studies (8/-) | 47.8 % | some concern | not evaluable | moderate | non important | - |
objective responses (ORR) (extension) | 2.16 [1.34, 3.48] | | > 1 | | 0% | 1 study (1/-) | 99.9 % | NA | not evaluable | | non important | - |
safety endpoints 00 |
AE (any grade) | 0.85 [0.13, 5.43] | | < 1 | | 94% | 5 studies (5/-) | 56.7 % | some concern | not evaluable | moderate | non important | - |
AE (grade 3-4) | 0.65 [0.27, 1.56] | | < 1 | | 98% | 6 studies (6/-) | 83.1 % | some concern | not evaluable | moderate | non important | - |
AE (grade 3-5) | 0.76 [0.19, 3.00] | | < 1 | | 96% | 2 studies (2/-) | 65.4 % | some concern | not evaluable | moderate | non important | - |
AE leading to death (grade 5) | 1.80 [1.18, 2.75] | | < 1 | | 50% | 7 studies (7/-) | 0.3 % | some concern | not evaluable | moderate | non important | - |
AE leading to treatment discontinuation (any grade) | 0.76 [0.40, 1.45] | | < 1 | | 94% | 8 studies (8/-) | 79.6 % | some concern | not evaluable | moderate | non important | - |
AE leading to treatment discontinuation (grade 3-4) | 0.85 [0.44, 1.65] | | < 1 | | 0% | 1 study (1/-) | 68.1 % | NA | not evaluable | | non important | - |
SAE (any grade) | 1.03 [0.84, 1.27] | | < 1 | | 58% | 5 studies (5/-) | 38.3 % | some concern | not evaluable | moderate | non important | - |
STRAE (any grade) | 0.73 [0.45, 1.18] | | < 1 | | 89% | 7 studies (7/-) | 89.9 % | some concern | not evaluable | moderate | non important | - |
TRAE (any grade) | 0.61 [0.16, 2.31] | | < 1 | | 98% | 8 studies (8/-) | 76.4 % | some concern | not evaluable | moderate | non important | - |
TRAE (grade 3-4) | 0.39 [0.16, 0.97] | | < 1 | | 98% | 9 studies (9/-) | 97.9 % | some concern | not evaluable | moderate | non important | - |
TRAE leading to death (grade 5) | 0.71 [0.36, 1.42] | | < 1 | | 42% | 8 studies (8/-) | 83.2 % | some concern | not evaluable | moderate | non important | - |
TRAE leading to discontinuation (any grade) | 0.57 [0.22, 1.47] | | < 1 | | 84% | 4 studies (4/-) | 87.8 % | some concern | not evaluable | moderate | non important | - |
TRAE (grade 3-4) endpoints 00 |
Abdominal pain TRAE (grade 3-4) | 3.64 [0.16, 81.12] | | < 1 | | 0% | 1 study (1/-) | 21.0 % | NA | not evaluable | | non important | - |
Acute kidney injury TRAE (grade 3-4) | 1.48 [0.15, 14.66] | | < 1 | | 0% | 2 studies (2/-) | 36.9 % | low | not evaluable | high | non important | - |
Adrenal insufficiency TRAE (grade 3-4) | 1.31 [0.29, 5.98] | | < 1 | | 0% | 6 studies (6/-) | 36.5 % | some concern | serious | moderate | non important | - |
Alopecia TRAE (grade 3-4) | 0.60 [0.06, 5.94] | | < 1 | | 0% | 2 studies (2/-) | 66.8 % | some concern | not evaluable | moderate | non important | - |
Anaemia TRAE (grade 3-4) | 0.17 [0.06, 0.49] | | < 1 | | 93% | 7 studies (7/-) | 99.9 % | some concern | serious | moderate | non important | - |
Arthralgia TRAE (grade 3-4) | 1.43 [0.11, 18.64] | | < 1 | | 0% | 2 studies (2/-) | 39.4 % | some concern | not evaluable | moderate | non important | - |
Arthritis TRAE (grade 3-4) | 0.95 [0.06, 15.28] | | < 1 | | 0% | 2 studies (2/-) | 51.3 % | some concern | not evaluable | moderate | non important | - |
Asthenia TRAE (grade 3-4) | 0.61 [0.31, 1.17] | | < 1 | | 47% | 9 studies (9/-) | 93.1 % | some concern | not evaluable | moderate | non important | - |
Blood creatinine increased TRAE (grade 3-4) | 0.95 [0.09, 10.48] | | < 1 | | 0% | 2 studies (2/-) | 51.7 % | low | not evaluable | high | non important | - |
Chills TRAE (grade 3-4) | 1.00 [0.02, 50.69] | | < 1 | | 0% | 1 study (1/-) | 49.9 % | NA | not evaluable | | non important | - |
Colitis TRAE (grade 3-4) | 2.50 [0.91, 6.91] | | < 1 | | 0% | 6 studies (6/-) | 3.8 % | some concern | not evaluable | moderate | non important | - |
Constipation TRAE (grade 3-4) | 0.21 [0.04, 1.05] | | < 1 | | 38% | 5 studies (5/-) | 97.1 % | some concern | not evaluable | moderate | non important | - |
Decreased appetite TRAE (grade 3-4) | 0.80 [0.34, 1.85] | | < 1 | | 0% | 7 studies (7/-) | 70.1 % | some concern | not evaluable | moderate | non important | - |
Dermatitis acneiform TRAE (grade 3-4) | 0.99 [0.02, 50.11] | | < 1 | | 0% | 1 study (1/-) | 50.2 % | NA | not evaluable | | non important | - |
Diabetes TRAE (grade 3-4) | 1.40 [0.27, 7.25] | | < 1 | | 0% | 5 studies (5/-) | 34.7 % | some concern | serious | moderate | non important | - |
Diarrhoea TRAE (grade 3-4) | 1.06 [0.54, 2.06] | | < 1 | | 0% | 6 studies (6/-) | 43.2 % | some concern | not evaluable | moderate | non important | - |
Dry skin TRAE (grade 3-4) | 1.00 [0.02, 50.69] | | < 1 | | 0% | 1 study (1/-) | 49.9 % | NA | not evaluable | | non important | - |
Dyspnoea TRAE (grade 3-4) | 3.64 [0.16, 81.12] | | < 1 | | 0% | 1 study (1/-) | 21.0 % | NA | not evaluable | | non important | - |
Eczema TRAE (grade 3-4) | 0.99 [0.02, 50.11] | | < 1 | | 0% | 1 study (1/-) | 50.2 % | NA | not evaluable | | non important | - |
Endocrine disorders TRAE (grade 3-4) | 1.99 [0.07, 59.38] | | < 1 | | 0% | 1 study (1/-) | 34.8 % | NA | not evaluable | | non important | - |
Erythema TRAE (grade 3-4) | 0.99 [0.02, 50.11] | | < 1 | | 0% | 1 study (1/-) | 50.2 % | NA | not evaluable | | non important | - |
Fatigue TRAE (grade 3-4) | 0.59 [0.33, 1.07] | | < 1 | | 33% | 9 studies (9/-) | 95.8 % | some concern | not evaluable | moderate | non important | - |
Febrile neutropenia TRAE (grade 3-4) | 0.06 [0.01, 0.30] | | < 1 | | 0% | 2 studies (2/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
Gastritis TRAE (grade 3-4) | 0.91 [0.02, 45.86] | | < 1 | | 0% | 1 study (1/-) | 51.9 % | NA | not evaluable | | non important | - |
Gastrointestinal disorders TRAE (grade 3-4) | 2.00 [0.50, 8.06] | | < 1 | | 0% | 1 study (1/-) | 16.5 % | NA | not evaluable | | non important | - |
Guillain-Barré syndrome TRAE (grade 3-4) | 1.91 [0.17, 21.12] | | < 1 | | 0% | 2 studies (2/-) | 30.0 % | some concern | not evaluable | moderate | non important | - |
Hepatitis TRAE (grade 3-4) | 3.07 [0.47, 19.99] | | < 1 | | 0% | 3 studies (3/-) | 12.2 % | some concern | not evaluable | moderate | non important | - |
Hypersensitivity TRAE (grade 3-4) | 0.45 [0.02, 13.55] | | < 1 | | 0% | 1 study (1/-) | 67.4 % | NA | not evaluable | | non important | - |
Hyperthyroidism TRAE (grade 3-4) | 1.18 [0.22, 6.46] | | < 1 | | 0% | 5 studies (5/-) | 42.4 % | some concern | serious | moderate | non important | - |
Hypophysitis TRAE (grade 3-4) | 2.72 [0.39, 19.09] | | < 1 | | 0% | 3 studies (3/-) | 15.9 % | some concern | not evaluable | moderate | non important | - |
Hypothyroidism TRAE (grade 3-4) | 2.19 [0.40, 12.08] | | < 1 | | 0% | 4 studies (4/-) | 18.6 % | some concern | not evaluable | moderate | non important | - |
Increase AST TRAE (grade 3-4) | 1.10 [0.20, 6.05] | | < 1 | | 0% | 2 studies (2/-) | 45.5 % | some concern | not evaluable | moderate | non important | - |
Increased ALT TRAE (grade 3-4) | 3.12 [0.50, 19.47] | | < 1 | | 0% | 2 studies (2/-) | 11.3 % | some concern | not evaluable | moderate | non important | - |
Increased lipase level TRAE (grade 3-4) | 9.73 [1.80, 52.75] | | < 1 | | 0% | 2 studies (2/-) | 0.4 % | some concern | not evaluable | moderate | non important | - |
Infusion-related reactions TRAE (grade 3-4) | 2.21 [0.29, 16.94] | | < 1 | | 0% | 3 studies (3/-) | 22.4 % | some concern | not evaluable | moderate | non important | - |
Leucopenia TRAE (grade 3-4) | 0.07 [0.00, 1.54] | | < 1 | | 84% | 3 studies (3/-) | 95.2 % | some concern | not evaluable | moderate | non important | - |
Maculopapular rash TRAE (grade 3-4) | 3.98 [0.18, 88.64] | | < 1 | | 0% | 1 study (1/-) | 19.4 % | NA | not evaluable | | non important | - |
Myocarditis TRAE (grade 3-4) | 2.19 [0.30, 15.87] | | < 1 | | 0% | 3 studies (3/-) | 21.9 % | some concern | not evaluable | moderate | non important | - |
Myositis TRAE (grade 3-4) | 1.41 [0.29, 6.75] | | < 1 | | 0% | 5 studies (5/-) | 33.5 % | some concern | not evaluable | moderate | non important | - |
Nausea TRAE (grade 3-4) | 0.59 [0.30, 1.14] | | < 1 | | 0% | 8 studies (8/-) | 94.2 % | some concern | not evaluable | moderate | non important | - |
Nephritis TRAE (grade 3-4) | 2.39 [0.61, 9.40] | | < 1 | | 0% | 6 studies (6/-) | 10.7 % | some concern | serious | moderate | non important | - |
Neutropenia TRAE (grade 3-4) | 0.08 [0.02, 0.34] | | < 1 | | 91% | 7 studies (7/-) | 100.0 % | some concern | serious | moderate | non important | - |
Pancreatitis TRAE (grade 3-4) | 2.68 [0.50, 14.20] | | < 1 | | 0% | 4 studies (4/-) | 12.4 % | some concern | not evaluable | moderate | non important | - |
Pancytopenia TRAE (grade 3-4) | 0.11 [0.01, 2.13] | | < 1 | | 0% | 1 study (1/-) | 92.5 % | NA | not evaluable | | non important | - |
Peripheral neuropathy TRAE (grade 3-4) | 0.15 [0.03, 0.83] | | < 1 | | 0% | 2 studies (2/-) | 98.5 % | some concern | not evaluable | moderate | non important | - |
Pneumonitis TRAE (grade 3-4) | 3.73 [1.22, 11.44] | | < 1 | | 0% | 6 studies (6/-) | 1.1 % | some concern | not evaluable | moderate | non important | - |
Pruritic rash TRAE (grade 3-4) | 0.95 [0.06, 15.19] | | < 1 | | 0% | 2 studies (2/-) | 51.5 % | low | not evaluable | high | non important | - |
Pruritus TRAE (grade 3-4) | 1.60 [0.46, 5.52] | | < 1 | | 0% | 8 studies (8/-) | 22.8 % | some concern | serious | moderate | non important | - |
Pyrexia TRAE (grade 3-4) | 0.40 [0.04, 4.57] | | < 1 | | 0% | 2 studies (2/-) | 76.8 % | some concern | not evaluable | moderate | non important | - |
Rash TRAE (grade 3-4) | 2.58 [0.82, 8.15] | | < 1 | | 0% | 7 studies (7/-) | 5.3 % | some concern | not evaluable | moderate | non important | - |
Renal and urinary disorders TRAE (grade 3-4) | 8.01 [0.42, 152.12] | | < 1 | | 0% | 1 study (1/-) | 8.5 % | NA | not evaluable | | non important | - |
Respiratory, thoracic and mediastinal disorders TRAE (grade 3-4) | 5.99 [0.30, 120.06] | | < 1 | | 0% | 1 study (1/-) | 12.4 % | NA | not evaluable | | non important | - |
Sarcoidosis TRAE (grade 3-4) | 1.05 [0.07, 16.88] | | < 1 | | 0% | 2 studies (2/-) | 48.5 % | some concern | not evaluable | moderate | non important | - |
Sepsis TRAE (grade 3-4) | 0.91 [0.06, 14.56] | | < 1 | | 0% | 1 study (1/-) | 52.7 % | NA | not evaluable | | non important | - |
Severe skin reaction TRAE (grade 3-4) | 1.36 [0.32, 5.68] | | < 1 | | 41% | 3 studies (3/-) | 33.8 % | some concern | not evaluable | moderate | non important | - |
Stevens-Johnson syndrome TRAE (grade 3-4) | 1.82 [0.06, 54.35] | | < 1 | | 0% | 1 study (1/-) | 36.7 % | NA | not evaluable | | non important | - |
Stomatitis TRAE (grade 3-4) | 0.91 [0.02, 45.86] | | < 1 | | 0% | 1 study (1/-) | 51.9 % | NA | not evaluable | | non important | - |
Thrombocytopenia TRAE (grade 3-4) | 0.20 [0.05, 0.71] | | < 1 | | 85% | 5 studies (5/-) | 99.4 % | some concern | serious | moderate | non important | - |
Thyroiditis TRAE (grade 3-4) | 1.16 [0.24, 5.50] | | < 1 | | 0% | 6 studies (6/-) | 42.7 % | some concern | serious | moderate | non important | - |
Urticaria TRAE (grade 3-4) | 0.99 [0.02, 50.11] | | < 1 | | 0% | 1 study (1/-) | 50.2 % | NA | not evaluable | | non important | - |
Uveitis TRAE (grade 3-4) | 1.00 [0.02, 50.69] | | < 1 | | 0% | 1 study (1/-) | 49.9 % | NA | not evaluable | | non important | - |
Vitiligo TRAE (grade 3-4) | 1.00 [0.02, 50.69] | | < 1 | | 0% | 1 study (1/-) | 49.9 % | NA | not evaluable | | non important | - |
Vomiting TRAE (grade 3-4) | 0.34 [0.06, 1.92] | | < 1 | | 60% | 3 studies (3/-) | 88.9 % | some concern | not evaluable | moderate | non important | - |
AE (grade 3-4) endpoints 00 |
hepatitis (Autoimmune) AE (grade 3-4) | 2.01 [0.07, 60.08] | | < 1 | | 0% | 1 study (1/-) | 34.6 % | NA | not evaluable | | non important | - |
Abdominal pain AE (grade 3-4) | 0.40 [0.10, 1.58] | | < 1 | | 0% | 1 study (1/-) | 90.3 % | NA | not evaluable | | non important | - |
Acute kidney injury AE (grade 3-4) | 2.27 [0.58, 8.88] | | < 1 | | 0% | 1 study (1/-) | 12.0 % | NA | not evaluable | | non important | - |
Alopecia AE (grade 3-4) | 0.16 [0.01, 3.17] | | < 1 | | 0% | 1 study (1/-) | 88.3 % | NA | not evaluable | | non important | - |
Anaemia AE (grade 3-4) | 0.51 [0.14, 1.84] | | < 1 | | 96% | 4 studies (4/-) | 84.7 % | some concern | not evaluable | moderate | non important | - |
Arthralgia AE (grade 3-4) | 0.78 [0.03, 18.57] | | < 1 | | 54% | 2 studies (2/-) | 56.1 % | some concern | not evaluable | moderate | non important | - |
Asthenia AE (grade 3-4) | 0.48 [0.16, 1.41] | | < 1 | | 75% | 4 studies (4/-) | 90.9 % | some concern | not evaluable | moderate | non important | - |
Back pain AE (grade 3-4) | 0.65 [0.22, 1.92] | | < 1 | | 0% | 2 studies (2/-) | 78.1 % | some concern | not evaluable | moderate | non important | - |
Blood and lymphatic system disorders AE (grade 3-4) | 0.24 [0.15, 0.40] | | < 1 | | 0% | 1 study (1/-) | 100.0 % | NA | not evaluable | | non important | - |
Blood creatinine increased AE (grade 3-4) | 1.92 [0.17, 21.35] | | < 1 | | 0% | 1 study (1/-) | 29.8 % | NA | not evaluable | | non important | - |
Cardiac disorders AE (grade 3-4) | 0.72 [0.16, 3.23] | | < 1 | | 0% | 1 study (1/-) | 66.8 % | NA | not evaluable | | non important | - |