| 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) | 0.66 [0.55, 0.81] | | < 1 | | 73% | 9 studies (9/-) | 100.0 % | low | not evaluable | high | crucial | - |
| deaths (OS) (extension) | 0.60 [0.47, 0.76] | | < 1 | | 80% | 4 studies (4/-) | 100.0 % | low | not evaluable | high | important | - |
| PFS (extension) | 0.50 [0.38, 0.65] | | < 1 | | 85% | 5 studies (5/-) | 100.0 % | low | not evaluable | high | important | - |
| progression or deaths (PFS) | 0.58 [0.45, 0.75] | | < 1 | | 87% | 8 studies (8/-) | 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 | - |
| DOR (extension) | 3.45 [1.46, 8.18] | | > 1 | | 0% | 1 study (1/-) | 99.8 % | NA | not evaluable | | non important | - |
| objective responses (ORR) | 2.71 [1.55, 4.72] | | > 1 | | 93% | 9 studies (9/-) | 100.0 % | low | serious | high | non important | - |
| objective responses (ORR) (extension) | 5.31 [3.93, 7.17] | | > 1 | | 55% | 5 studies (5/-) | 100.0 % | low | not evaluable | high | non important | - |
safety endpoints 00 |
| AE (any grade) | 2.55 [0.68, 9.53] | | < 1 | | 84% | 3 studies (3/-) | 8.3 % | some concern | not evaluable | moderate | non important | - |
| AE (grade 3-4) | 1.84 [0.81, 4.18] | | < 1 | | 93% | 3 studies (3/-) | 7.3 % | some concern | not evaluable | moderate | non important | - |
| AE leading to death (grade 5) | 1.50 [0.89, 2.52] | | < 1 | | 0% | 4 studies (4/-) | 6.3 % | some concern | not evaluable | moderate | non important | - |
| AE leading to treatment discontinuation (any grade) | 1.37 [0.38, 5.00] | | < 1 | | 84% | 3 studies (3/-) | 31.7 % | low | not evaluable | high | non important | - |
| AE leading to treatment discontinuation (grade 3-4) | 0.61 [0.29, 1.28] | | < 1 | | 0% | 1 study (1/-) | 90.5 % | NA | not evaluable | | non important | - |
| SAE (any grade) | 1.53 [0.36, 6.48] | | < 1 | | 96% | 2 studies (2/-) | 28.1 % | some concern | not evaluable | moderate | non important | - |
| SAE (grade 3-4) | 0.74 [0.47, 1.17] | | < 1 | | 0% | 1 study (1/-) | 90.4 % | NA | not evaluable | | non important | - |
| STRAE (any grade) | 1.20 [0.86, 1.66] | | < 1 | | 0% | 2 studies (2/-) | 14.4 % | low | not evaluable | high | non important | - |
| STRAE (grade 3-4) | 0.99 [0.44, 2.27] | | < 1 | | 0% | 1 study (1/-) | 50.5 % | NA | not evaluable | | non important | - |
| TRAE (any grade) | 1.55 [0.83, 2.88] | | < 1 | | 78% | 6 studies (6/-) | 8.2 % | low | not evaluable | high | non important | - |
| TRAE (grade 3-4) | 1.87 [0.89, 3.92] | | < 1 | | 95% | 6 studies (6/-) | 5.0 % | low | not evaluable | high | non important | - |
| TRAE leading to death (grade 5) | 2.84 [0.61, 13.25] | | < 1 | | 0% | 4 studies (4/-) | 9.3 % | some concern | not evaluable | moderate | non important | - |
| TRAE leading to discontinuation (any grade) | 2.73 [1.08, 6.91] | | < 1 | | 93% | 4 studies (4/-) | 1.7 % | low | not evaluable | high | non important | - |
| TRAE leading to discontinuation (grade 3-4) | 2.30 [0.82, 6.41] | | < 1 | | 93% | 4 studies (4/-) | 5.6 % | low | not evaluable | high | non important | - |
TRAE (grade 3-4) endpoints 00 |
| Abdominal pain TRAE (grade 3-4) | 0.53 [0.13, 2.13] | | < 1 | | 0% | 5 studies (5/-) | 81.5 % | low | not evaluable | high | non important | - |
| Adrenal insufficiency TRAE (grade 3-4) | 2.30 [0.79, 6.68] | | < 1 | | 15% | 5 studies (5/-) | 6.3 % | low | not evaluable | high | non important | - |
| Alopecia TRAE (grade 3-4) | 1.00 [0.02, 50.40] | | < 1 | | 0% | 1 study (1/-) | 50.1 % | NA | not evaluable | | non important | - |
| Anaemia TRAE (grade 3-4) | 1.00 [0.02, 50.40] | | < 1 | | 0% | 1 study (1/-) | 50.1 % | NA | not evaluable | | non important | - |
| Arthralgia TRAE (grade 3-4) | 1.55 [0.65, 3.71] | | < 1 | | 0% | 6 studies (6/-) | 16.3 % | low | not evaluable | high | non important | - |
| Asthenia TRAE (grade 3-4) | 0.96 [0.35, 2.65] | | < 1 | | 0% | 6 studies (6/-) | 53.1 % | low | serious | high | non important | - |
| Blood creatinine increased TRAE (grade 3-4) | 0.61 [0.02, 18.27] | | < 1 | | 0% | 1 study (1/-) | 61.1 % | NA | not evaluable | | non important | - |
| Chills TRAE (grade 3-4) | 0.49 [0.01, 24.92] | | < 1 | | 0% | 1 study (1/-) | 63.7 % | NA | not evaluable | | 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) | 1.35 [0.29, 6.37] | | < 1 | | 89% | 4 studies (4/-) | 35.3 % | low | not evaluable | high | non important | - |
| Constipation TRAE (grade 3-4) | 0.99 [0.08, 12.95] | | < 1 | | 0% | 2 studies (2/-) | 50.4 % | low | not evaluable | high | non important | - |
| Cough TRAE (grade 3-4) | 1.00 [0.18, 5.57] | | < 1 | | 0% | 4 studies (4/-) | 50.2 % | low | not evaluable | high | non important | - |
| Decreased appetite TRAE (grade 3-4) | 1.59 [0.46, 5.54] | | < 1 | | 0% | 6 studies (6/-) | 23.4 % | low | not evaluable | high | non important | - |
| Diarrhoea TRAE (grade 3-4) | 1.18 [0.59, 2.36] | | < 1 | | 67% | 6 studies (6/-) | 31.6 % | low | not evaluable | high | non important | - |
| Dry skin TRAE (grade 3-4) | 1.42 [0.69, 2.95] | | < 1 | | 0% | 5 studies (5/-) | 17.1 % | low | not evaluable | high | non important | - |
| Dyspnoea TRAE (grade 3-4) | 3.27 [0.80, 13.40] | | < 1 | | 0% | 4 studies (4/-) | 5.0 % | low | not evaluable | high | non important | - |
| Endocrine disorders TRAE (grade 3-4) | 1.24 [0.23, 6.63] | | < 1 | | 0% | 1 study (1/-) | 40.3 % | NA | not evaluable | | 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) | 0.98 [0.02, 49.62] | | < 1 | | 0% | 1 study (1/-) | 50.4 % | NA | not evaluable | | non important | - |
| Fatigue TRAE (grade 3-4) | 2.84 [1.39, 5.84] | | < 1 | | 4% | 6 studies (6/-) | 0.2 % | low | not evaluable | high | non important | - |
| Gastrointestinal disorders TRAE (grade 3-4) | 2.22 [0.77, 6.34] | | < 1 | | 0% | 1 study (1/-) | 6.9 % | NA | not evaluable | | non important | - |
| Headache TRAE (grade 3-4) | 1.67 [0.42, 6.59] | | < 1 | | 0% | 5 studies (5/-) | 23.2 % | low | not evaluable | high | non important | - |
| Hepatitis TRAE (grade 3-4) | 4.81 [1.19, 19.40] | | < 1 | | 0% | 5 studies (5/-) | 1.4 % | low | serious | high | non important | - |
| Hepatobiliary disorders TRAE (grade 3-4) | 15.93 [0.93, 273.74] | | < 1 | | 0% | 1 study (1/-) | 3.0 % | NA | not evaluable | | non important | - |
| Hypersensitivity TRAE (grade 3-4) | 1.00 [0.02, 50.40] | | < 1 | | 0% | 1 study (1/-) | 50.1 % | NA | not evaluable | | non important | - |
| Hyperthyroidism TRAE (grade 3-4) | 2.90 [0.75, 11.29] | | < 1 | | 0% | 6 studies (6/-) | 6.2 % | low | serious | high | non important | - |
| Hypophysitis TRAE (grade 3-4) | 0.84 [0.27, 2.68] | | < 1 | | 38% | 4 studies (4/-) | 61.2 % | low | not evaluable | high | non important | - |
| Hypothyroidism TRAE (grade 3-4) | 1.22 [0.23, 6.34] | | < 1 | | 0% | 5 studies (5/-) | 40.8 % | low | serious | high | non important | - |
| Increase AST TRAE (grade 3-4) | 4.87 [2.20, 10.77] | | < 1 | | 4% | 5 studies (5/-) | 0.0 % | low | not evaluable | high | non important | - |
| Increased ALT TRAE (grade 3-4) | 3.64 [1.41, 9.42] | | < 1 | | 52% | 5 studies (5/-) | 0.4 % | low | not evaluable | high | non important | - |
| Increased lipase level TRAE (grade 3-4) | 1.80 [1.02, 3.16] | | < 1 | | 66% | 5 studies (5/-) | 2.1 % | low | not evaluable | high | non important | - |
| Infusion-related reactions TRAE (grade 3-4) | 1.00 [0.02, 50.40] | | < 1 | | 0% | 1 study (1/-) | 50.1 % | NA | not evaluable | | non important | - |
| Leucopenia TRAE (grade 3-4) | 0.12 [0.01, 2.33] | | < 1 | | 0% | 1 study (1/-) | 91.7 % | NA | not evaluable | | non important | - |
| Maculopapular rash TRAE (grade 3-4) | 1.65 [1.02, 2.69] | | < 1 | | 0% | 6 studies (6/-) | 2.2 % | low | serious | high | non important | - |
| Myalgia TRAE (grade 3-4) | 1.46 [0.40, 5.27] | | < 1 | | 0% | 6 studies (6/-) | 28.4 % | low | not evaluable | high | non important | - |
| Nausea TRAE (grade 3-4) | 1.06 [0.25, 4.41] | | < 1 | | 47% | 6 studies (6/-) | 47.1 % | low | not evaluable | high | non important | - |
| Neutropenia TRAE (grade 3-4) | 0.05 [0.00, 0.92] | | < 1 | | 0% | 1 study (1/-) | 97.7 % | NA | not evaluable | | non important | - |
| Pancreatitis TRAE (grade 3-4) | 5.93 [0.30, 118.96] | | < 1 | | 0% | 1 study (1/-) | 12.5 % | NA | not evaluable | | 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) | 1.00 [0.02, 50.40] | | < 1 | | 0% | 1 study (1/-) | 50.1 % | NA | not evaluable | | 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) | 2.10 [0.68, 6.47] | | < 1 | | 0% | 5 studies (5/-) | 9.8 % | low | not evaluable | high | non important | - |
| Pruritic rash TRAE (grade 3-4) | 0.83 [0.12, 5.93] | | < 1 | | 0% | 4 studies (4/-) | 57.2 % | low | not evaluable | high | non important | - |
| Pruritus TRAE (grade 3-4) | 3.01 [1.06, 8.55] | | < 1 | | 0% | 6 studies (6/-) | 1.9 % | low | serious | high | non important | - |
| Pyrexia TRAE (grade 3-4) | 1.43 [0.51, 4.01] | | < 1 | | 0% | 6 studies (6/-) | 24.6 % | low | not evaluable | high | non important | - |
| Rash TRAE (grade 3-4) | 1.56 [0.64, 3.79] | | < 1 | | 46% | 6 studies (6/-) | 16.5 % | low | not evaluable | high | non important | - |
| Renal and urinary disorders TRAE (grade 3-4) | 0.98 [0.03, 29.71] | | < 1 | | 0% | 1 study (1/-) | 50.5 % | NA | not evaluable | | non important | - |
| Respiratory, thoracic and mediastinal disorders TRAE (grade 3-4) | 1.48 [0.15, 14.67] | | < 1 | | 0% | 1 study (1/-) | 36.9 % | NA | not evaluable | | non important | - |
| Skin and subcutaneous tissue disorders TRAE (grade 3-4) | 9.64 [0.55, 170.02] | | < 1 | | 0% | 1 study (1/-) | 6.3 % | NA | not evaluable | | non important | - |
| Thrombocytopenia TRAE (grade 3-4) | 0.05 [0.00, 0.82] | | < 1 | | 0% | 1 study (1/-) | 98.1 % | NA | not evaluable | | non important | - |
| Thyroiditis TRAE (grade 3-4) | 1.65 [0.21, 12.81] | | < 1 | | 0% | 3 studies (3/-) | 31.7 % | low | not evaluable | high | non important | - |
| Vitiligo TRAE (grade 3-4) | 0.88 [0.17, 4.57] | | < 1 | | 0% | 5 studies (5/-) | 56.1 % | low | not evaluable | high | non important | - |
| Vomiting TRAE (grade 3-4) | 1.75 [0.61, 5.02] | | < 1 | | 19% | 6 studies (6/-) | 14.9 % | low | not evaluable | high | non important | - |
| Weight decreased TRAE (grade 3-4) | 0.60 [0.08, 4.66] | | < 1 | | 0% | 3 studies (3/-) | 68.6 % | low | not evaluable | high | non important | - |
AE (grade 3-4) endpoints 00 |
| Abdominal pain AE (grade 3-4) | 2.45 [0.65, 9.22] | | < 1 | | 28% | 2 studies (2/-) | 9.3 % | some concern | not evaluable | moderate | non important | - |
| Anaemia AE (grade 3-4) | 1.74 [0.50, 6.04] | | < 1 | | 0% | 1 study (1/-) | 19.1 % | NA | not evaluable | | non important | - |
| Arthralgia AE (grade 3-4) | 0.98 [0.02, 49.71] | | < 1 | | 0% | 1 study (1/-) | 50.4 % | NA | not evaluable | | non important | - |
| Asthenia AE (grade 3-4) | 0.56 [0.04, 8.91] | | < 1 | | 69% | 2 studies (2/-) | 65.8 % | some concern | not evaluable | moderate | non important | - |
| Constipation AE (grade 3-4) | 0.98 [0.17, 5.69] | | < 1 | | 0% | 2 studies (2/-) | 50.8 % | some concern | not evaluable | moderate | non important | - |
| Cough AE (grade 3-4) | 1.97 [0.07, 58.81] | | < 1 | | 0% | 1 study (1/-) | 35.0 % | NA | not evaluable | | non important | - |
| Decreased appetite AE (grade 3-4) | 8.48 [1.48, 48.62] | | < 1 | | 0% | 2 studies (2/-) | 0.8 % | some concern | not evaluable | moderate | non important | - |
| Dermatitis acneiform AE (grade 3-4) | 22.68 [1.32, 388.47] | | < 1 | | 0% | 1 study (1/-) | 1.7 % | NA | not evaluable | | non important | - |
| Diarrhoea AE (grade 3-4) | 4.44 [1.47, 13.42] | | < 1 | | 0% | 1 study (1/-) | 0.4 % | NA | not evaluable | | non important | - |
| Dyspnoea AE (grade 3-4) | 4.00 [0.84, 18.98] | | < 1 | | 0% | 1 study (1/-) | 4.1 % | NA | not evaluable | | non important | - |
| Fatigue AE (grade 3-4) | 2.95 [1.30, 6.71] | | < 1 | | 0% | 2 studies (2/-) | 0.5 % | some concern | not evaluable | moderate | non important | - |
| Headache AE (grade 3-4) | 1.97 [0.28, 14.03] | | < 1 | | 0% | 2 studies (2/-) | 25.1 % | some concern | not evaluable | moderate | non important | - |
| Hypertension AE (grade 3-4) | 1.77 [0.73, 4.30] | | < 1 | | 0% | 1 study (1/-) | 10.5 % | NA | not evaluable | | non important | - |
| Hypothyroidism AE (grade 3-4) | 1.22 [0.02, 61.84] | | < 1 | | 0% | 1 study (1/-) | 46.1 % | NA | not evaluable | | non important | - |
| Increase AST AE (grade 3-4) | 3.00 [0.60, 15.03] | | < 1 | | 0% | 1 study (1/-) | 9.1 % | NA | not evaluable | | non important | - |
| Increased ALT AE (grade 3-4) | 1.99 [0.49, 8.06] | | < 1 | | 0% | 1 study (1/-) | 16.8 % | NA | not evaluable | | non important | - |
| Increased Lipase Level AE (grade 3-4) | 2.00 [0.59, 6.74] | | < 1 | | 0% | 1 study (1/-) | 13.2 % | NA | not evaluable | | non important | - |
| Nausea AE (grade 3-4) | 2.23 [0.43, 11.65] | | < 1 | | 39% | 2 studies (2/-) | 17.1 % | some concern | not evaluable | moderate | non important | - |
| Neutropenia AE (grade 3-4) | 0.03 [0.00, 0.19] | | < 1 | | 0% | 1 study (1/-) | 100.0 % | NA | not evaluable | | non important | - |
| Peripheral oedema AE (grade 3-4) | 2.70 [0.49, 14.83] | | < 1 | | 0% | 2 studies (2/-) | 12.7 % | some concern | not evaluable | moderate | non important | - |
