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) | 0.76 [0.67, 0.85] | | < 1 | | 70% | 13 studies (13/-) | 100.0 % | some concern | critical | moderate | crucial | - |
deaths (OS) (extension) | 0.68 [0.59, 0.79] | | < 1 | | 60% | 5 studies (5/-) | 100.0 % | some concern | not evaluable | moderate | important | - |
PFS (extension) | 0.66 [0.48, 0.91] | | < 1 | | 94% | 5 studies (5/-) | 99.5 % | some concern | serious | moderate | important | - |
progression or deaths (PFS) | 0.70 [0.58, 0.84] | | < 1 | | 88% | 12 studies (12/-) | 100.0 % | some concern | low | moderate | important | - |
objective responses (ORR) | 1.71 [1.25, 2.34] | | > 1 | | 86% | 12 studies (12/-) | 100.0 % | some concern | low | moderate | non important | - |
objective responses (ORR) (extension) | 1.87 [0.98, 3.57] | | > 1 | | 90% | 4 studies (4/-) | 97.1 % | some concern | not evaluable | moderate | non important | - |
safety endpoints 00 |
AE (any grade) | 0.52 [0.30, 0.90] | | < 1 | | 67% | 9 studies (9/-) | 99.0 % | some concern | serious | moderate | non important | - |
AE (grade 3-4) | 0.65 [0.44, 0.96] | | < 1 | | 89% | 9 studies (9/-) | 98.6 % | some concern | not evaluable | moderate | non important | - |
AE leading to death (grade 5) | 1.16 [0.81, 1.66] | | < 1 | | 37% | 9 studies (9/-) | 20.4 % | some concern | not evaluable | moderate | non important | - |
AE leading to treatment discontinuation (any grade) | 1.07 [0.70, 1.63] | | < 1 | | 80% | 9 studies (9/-) | 37.8 % | some concern | not evaluable | 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) | 1.28 [0.96, 1.69] | | < 1 | | 22% | 4 studies (4/-) | 4.4 % | some concern | not evaluable | moderate | non important | - |
STRAE (any grade) | 0.99 [0.65, 1.49] | | < 1 | | 80% | 7 studies (7/-) | 52.7 % | some concern | not evaluable | moderate | non important | - |
STRAE (grade 3-4) | 1.04 [0.64, 1.67] | | < 1 | | 80% | 5 studies (5/-) | 44.2 % | some concern | serious | moderate | non important | - |
TRAE (any grade) | 0.31 [0.21, 0.47] | | < 1 | | 86% | 9 studies (9/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
TRAE (grade 3-4) | 0.36 [0.22, 0.57] | | < 1 | | 93% | 9 studies (9/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
TRAE leading to death (grade 5) | 1.07 [0.67, 1.69] | | < 1 | | 0% | 9 studies (9/-) | 39.3 % | some concern | not evaluable | moderate | non important | - |
TRAE leading to discontinuation (any grade) | 1.11 [0.71, 1.73] | | < 1 | | 77% | 8 studies (8/-) | 32.5 % | some concern | not evaluable | moderate | non important | - |
TRAE leading to discontinuation (grade 3-4) | 1.62 [1.01, 2.61] | | < 1 | | 70% | 6 studies (6/-) | 2.3 % | some concern | not evaluable | moderate | non important | - |
TRAE (grade 3-4) endpoints 00 |
Acute kidney injury TRAE (grade 3-4) | 1.61 [0.14, 17.97] | | < 1 | | 0% | 2 studies (2/-) | 35.0 % | some concern | not evaluable | moderate | non important | - |
Adrenal insufficiency TRAE (grade 3-4) | 2.37 [0.73, 7.72] | | < 1 | | 0% | 7 studies (7/-) | 7.6 % | some concern | not evaluable | moderate | non important | - |
Alopecia TRAE (grade 3-4) | 0.35 [0.06, 2.07] | | < 1 | | 0% | 4 studies (4/-) | 87.6 % | some concern | not evaluable | moderate | non important | - |
Anaemia TRAE (grade 3-4) | 0.06 [0.02, 0.19] | | < 1 | | 76% | 8 studies (8/-) | 100.0 % | some concern | serious | moderate | non important | - |
Arthralgia TRAE (grade 3-4) | 0.97 [0.02, 48.81] | | < 1 | | 0% | 1 study (1/-) | 50.7 % | NA | not evaluable | | non important | - |
Asthenia TRAE (grade 3-4) | 0.25 [0.12, 0.52] | | < 1 | | 0% | 7 studies (7/-) | 100.0 % | some concern | not evaluable | moderate | non important | - |
Blood creatinine increased TRAE (grade 3-4) | 0.98 [0.09, 10.85] | | < 1 | | 0% | 2 studies (2/-) | 50.7 % | some concern | not evaluable | moderate | non important | - |
Colitis TRAE (grade 3-4) | 3.96 [1.54, 10.21] | | < 1 | | 0% | 10 studies (10/-) | 0.2 % | some concern | low | moderate | non important | - |
Constipation TRAE (grade 3-4) | 0.69 [0.17, 2.76] | | < 1 | | 0% | 7 studies (7/-) | 70.1 % | some concern | serious | moderate | non important | - |
Decreased appetite TRAE (grade 3-4) | 0.56 [0.31, 1.03] | | < 1 | | 0% | 8 studies (8/-) | 96.9 % | some concern | not evaluable | moderate | non important | - |
Dermatitis acneiform TRAE (grade 3-4) | 0.50 [0.02, 15.30] | | < 1 | | 0% | 1 study (1/-) | 65.1 % | NA | not evaluable | | non important | - |
Diabetes TRAE (grade 3-4) | 1.40 [0.24, 8.12] | | < 1 | | 0% | 4 studies (4/-) | 35.3 % | some concern | not evaluable | moderate | non important | - |
Diarrhoea TRAE (grade 3-4) | 2.24 [1.19, 4.20] | | < 1 | | 3% | 10 studies (10/-) | 0.6 % | some concern | low | moderate | non important | - |
Dysgeusia TRAE (grade 3-4) | 0.98 [0.06, 15.72] | | < 1 | | 0% | 2 studies (2/-) | 50.6 % | some concern | not evaluable | moderate | non important | - |
Dyspepsia TRAE (grade 3-4) | 0.50 [0.02, 15.30] | | < 1 | | 0% | 1 study (1/-) | 65.1 % | NA | not evaluable | | non important | - |
Dyspnoea TRAE (grade 3-4) | 2.56 [0.11, 57.33] | | < 1 | | 0% | 1 study (1/-) | 27.9 % | NA | not evaluable | | non important | - |
Fatigue TRAE (grade 3-4) | 0.65 [0.35, 1.22] | | < 1 | | 36% | 8 studies (8/-) | 90.9 % | some concern | not evaluable | moderate | non important | - |
Febrile neutropenia TRAE (grade 3-4) | 0.46 [0.03, 7.18] | | < 1 | | 71% | 2 studies (2/-) | 70.7 % | 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 | - |
Hepatitis TRAE (grade 3-4) | 4.95 [1.86, 13.14] | | < 1 | | 0% | 8 studies (8/-) | 0.1 % | some concern | not evaluable | moderate | non important | - |
Hypersensitivity TRAE (grade 3-4) | 1.27 [0.04, 38.28] | | < 1 | | 0% | 1 study (1/-) | 44.5 % | NA | not evaluable | | non important | - |
Hypertension TRAE (grade 3-4) | 1.27 [0.11, 14.23] | | < 1 | | 0% | 1 study (1/-) | 42.2 % | NA | not evaluable | | non important | - |
Hyperthyroidism TRAE (grade 3-4) | 0.97 [0.29, 3.23] | | < 1 | | 0% | 10 studies (10/-) | 51.8 % | some concern | critical | moderate | non important | - |
Hypophysitis TRAE (grade 3-4) | 1.76 [0.43, 7.22] | | < 1 | | 0% | 6 studies (6/-) | 21.8 % | some concern | serious | moderate | non important | - |
Hypothyroidism TRAE (grade 3-4) | 1.59 [0.57, 4.43] | | < 1 | | 0% | 12 studies (12/-) | 19.0 % | some concern | critical | moderate | non important | - |
Increase AST TRAE (grade 3-4) | 1.66 [0.45, 6.18] | | < 1 | | 0% | 4 studies (4/-) | 22.5 % | some concern | not evaluable | moderate | non important | - |
Increased ALT TRAE (grade 3-4) | 1.95 [0.94, 4.04] | | < 1 | | 0% | 6 studies (6/-) | 3.7 % | some concern | not evaluable | moderate | non important | - |
Increased lipase level TRAE (grade 3-4) | 5.43 [1.81, 16.31] | | < 1 | | 0% | 3 studies (3/-) | 0.1 % | some concern | not evaluable | moderate | non important | - |
Infusion-related reactions TRAE (grade 3-4) | 0.46 [0.12, 1.73] | | < 1 | | 0% | 6 studies (6/-) | 87.5 % | some concern | serious | moderate | non important | - |
Leucopenia TRAE (grade 3-4) | 0.08 [0.02, 0.34] | | < 1 | | 0% | 4 studies (4/-) | 100.0 % | 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) | 1.94 [0.06, 57.80] | | < 1 | | 0% | 1 study (1/-) | 35.4 % | NA | not evaluable | | 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) | 0.68 [0.07, 6.51] | | < 1 | | 0% | 3 studies (3/-) | 63.2 % | some concern | not evaluable | moderate | non important | - |
Nausea TRAE (grade 3-4) | 0.31 [0.12, 0.77] | | < 1 | | 12% | 8 studies (8/-) | 99.4 % | some concern | serious | moderate | non important | - |
Nephritis TRAE (grade 3-4) | 1.93 [0.46, 8.10] | | < 1 | | 0% | 6 studies (6/-) | 18.4 % | some concern | serious | moderate | non important | - |
Neutropenia TRAE (grade 3-4) | 0.04 [0.01, 0.22] | | < 1 | | 82% | 8 studies (8/-) | 100.0 % | some concern | serious | moderate | non important | - |
Pancreatitis TRAE (grade 3-4) | 1.87 [0.35, 9.94] | | < 1 | | 0% | 4 studies (4/-) | 23.2 % | some concern | not evaluable | moderate | non important | - |
Peripheral neuropathy TRAE (grade 3-4) | 0.44 [0.06, 3.02] | | < 1 | | 0% | 3 studies (3/-) | 79.7 % | some concern | not evaluable | moderate | non important | - |
Peripheral oedema TRAE (grade 3-4) | 1.14 [0.09, 14.91] | | < 1 | | 0% | 2 studies (2/-) | 46.0 % | some concern | not evaluable | moderate | non important | - |
Peripheral sensory neuropathy TRAE (grade 3-4) | 0.08 [0.00, 1.43] | | < 1 | | 0% | 1 study (1/-) | 95.5 % | NA | not evaluable | | non important | - |
Pneumonia TRAE (grade 3-4) | 0.87 [0.09, 8.46] | | < 1 | | 0% | 2 studies (2/-) | 54.8 % | some concern | not evaluable | moderate | non important | - |
Pneumonitis TRAE (grade 3-4) | 2.85 [1.42, 5.71] | | < 1 | | 1% | 10 studies (10/-) | 0.2 % | some concern | low | moderate | non important | - |
Pruritic rash TRAE (grade 3-4) | 1.27 [0.04, 38.28] | | < 1 | | 0% | 1 study (1/-) | 44.5 % | NA | not evaluable | | non important | - |
Pruritus TRAE (grade 3-4) | 1.41 [0.37, 5.37] | | < 1 | | 0% | 7 studies (7/-) | 30.6 % | some concern | serious | moderate | non important | - |
Pyrexia TRAE (grade 3-4) | 0.50 [0.06, 3.92] | | < 1 | | 0% | 3 studies (3/-) | 74.2 % | some concern | not evaluable | moderate | non important | - |
Rash TRAE (grade 3-4) | 1.36 [0.62, 2.97] | | < 1 | | 0% | 10 studies (10/-) | 22.2 % | 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 | - |
Severe skin reaction TRAE (grade 3-4) | 3.88 [0.61, 24.61] | | < 1 | | 62% | 3 studies (3/-) | 7.6 % | 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) | 0.74 [0.16, 3.42] | | < 1 | | 0% | 5 studies (5/-) | 65.0 % | some concern | not evaluable | moderate | non important | - |
Thrombocytopenia TRAE (grade 3-4) | 0.10 [0.02, 0.43] | | < 1 | | 70% | 7 studies (7/-) | 99.9 % | some concern | serious | moderate | non important | - |
Thyroiditis TRAE (grade 3-4) | 0.74 [0.10, 5.26] | | < 1 | | 0% | 4 studies (4/-) | 61.8 % | some concern | not evaluable | moderate | non important | - |
Vomiting TRAE (grade 3-4) | 0.36 [0.13, 1.01] | | < 1 | | 19% | 7 studies (7/-) | 97.4 % | some concern | serious | moderate | non important | - |
Weight decreased TRAE (grade 3-4) | 1.27 [0.04, 38.28] | | < 1 | | 0% | 1 study (1/-) | 44.5 % | NA | not evaluable | | non important | - |
AE (grade 3-4) endpoints 00 |
hepatitis (Autoimmune) AE (grade 3-4) | 5.05 [0.55, 46.09] | | < 1 | | 0% | 2 studies (2/-) | 7.7 % | low | not evaluable | high | 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 | - |
Alopecia AE (grade 3-4) | 0.42 [0.09, 1.95] | | < 1 | | 0% | 4 studies (4/-) | 86.4 % | some concern | not evaluable | moderate | non important | - |
Anaemia AE (grade 3-4) | 0.20 [0.08, 0.55] | | < 1 | | 92% | 6 studies (6/-) | 99.9 % | some concern | serious | moderate | non important | - |
Arthralgia AE (grade 3-4) | 1.52 [0.33, 6.97] | | < 1 | | 0% | 2 studies (2/-) | 29.6 % | low | not evaluable | high | non important | - |
Asthenia AE (grade 3-4) | 0.93 [0.61, 1.43] | | < 1 | | 0% | 6 studies (6/-) | 62.2 % | some concern | not evaluable | moderate | non important | - |
Back pain AE (grade 3-4) | 0.48 [0.13, 1.77] | | < 1 | | 0% | 3 studies (3/-) | 86.3 % | some concern | not evaluable | moderate | non important | - |
Blood creatinine increased AE (grade 3-4) | 0.48 [0.02, 14.38] | | < 1 | | 0% | 1 study (1/-) | 66.1 % | NA | not evaluable | | non important | - |
Colitis AE (grade 3-4) | 2.04 [0.50, 8.23] | | < 1 | | 0% | 1 study (1/-) | 16.0 % | NA | not evaluable | | non important | - |
Constipation AE (grade 3-4) | 1.21 [0.48, 3.01] | | < 1 | | 0% | 6 studies (6/-) | 34.5 % | some concern | not evaluable | moderate | non important | - |
Cough AE (grade 3-4) | 0.90 [0.25, 3.23] | | < 1 | | 0% | 5 studies (5/-) | 56.4 % | low | not evaluable | high | non important | - |
Decreased appetite AE (grade 3-4) | 1.49 [0.78, 2.85] | | < 1 | | 0% | 6 studies (6/-) | 11.3 % | some concern | not evaluable | moderate | non important | - |
Diarrhoea AE (grade 3-4) | 1.08 [0.51, 2.29] | | < 1 | | 44% | 6 studies (6/-) | 42.0 % | some concern | serious | moderate | non important | - |
Dyspnoea AE (grade 3-4) | 1.10 [0.66, 1.84] | | < 1 | | 0% | 6 studies (6/-) | 35.6 % | some concern | serious | moderate | non important | - |
Epistaxis AE (grade 3-4) | 1.01 [0.02, 50.94] | | < 1 | | 0% | 1 study (1/-) | 49.9 % | NA | not evaluable | | non important | - |