| 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) | 0.69 [0.57, 0.83] | | < 1 | | 65% | 5 studies (5/-) | 100.0 % | low | not evaluable | high | crucial | - |
| deaths (OS) (extension) | 0.65 [0.50, 0.84] | | < 1 | | 79% | 3 studies (3/-) | 100.0 % | low | not evaluable | high | important | - |
| PFS (extension) | 0.52 [0.37, 0.71] | | < 1 | | 87% | 4 studies (4/-) | 100.0 % | low | not evaluable | high | important | - |
| progression or deaths (PFS) | 0.53 [0.39, 0.72] | | < 1 | | 75% | 4 studies (4/-) | 100.0 % | low | not evaluable | high | important | - |
| objective responses (ORR) | 3.55 [1.58, 8.01] | | > 1 | | 93% | 5 studies (5/-) | 99.9 % | low | not evaluable | high | non important | - |
| objective responses (ORR) (extension) | 5.60 [3.83, 8.17] | | > 1 | | 65% | 4 studies (4/-) | 100.0 % | low | not evaluable | high | non important | - |
safety endpoints 00 |
| AE (any grade) | 2.22 [1.12, 4.38] | | < 1 | | 0% | 1 study (1/-) | 1.1 % | NA | not evaluable | | non important | - |
| AE (grade 3-4) | 1.84 [1.35, 2.52] | | < 1 | | 0% | 1 study (1/-) | 0.0 % | NA | not evaluable | | non important | - |
| AE leading to death (grade 5) | 1.71 [0.85, 3.45] | | < 1 | | 0% | 1 study (1/-) | 6.8 % | NA | not evaluable | | non important | - |
| AE leading to treatment discontinuation (any grade) | 97.13 [5.95, 1585.40] | | < 1 | | 0% | 1 study (1/-) | 0.1 % | NA | not evaluable | | non important | - |
| SAE (any grade) | 3.19 [2.19, 4.65] | | < 1 | | 0% | 1 study (1/-) | 0.0 % | NA | not evaluable | | non important | - |
| TRAE (any grade) | 1.91 [0.84, 4.34] | | < 1 | | 82% | 4 studies (4/-) | 6.0 % | low | not evaluable | high | non important | - |
| TRAE (grade 3-4) | 2.63 [1.01, 6.84] | | < 1 | | 95% | 4 studies (4/-) | 2.4 % | 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) | 0.48 [0.11, 2.14] | | < 1 | | 0% | 4 studies (4/-) | 83.1 % | 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 | - |
| Arthralgia TRAE (grade 3-4) | 1.91 [0.41, 8.82] | | < 1 | | 0% | 4 studies (4/-) | 20.4 % | low | not evaluable | high | non important | - |
| Asthenia TRAE (grade 3-4) | 0.59 [0.15, 2.28] | | < 1 | | 0% | 4 studies (4/-) | 77.9 % | low | not evaluable | high | 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 | - |
| 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) | 0.98 [0.03, 29.71] | | < 1 | | 0% | 1 study (1/-) | 50.5 % | NA | not evaluable | | non important | - |
| Cough TRAE (grade 3-4) | 1.00 [0.15, 6.76] | | < 1 | | 0% | 3 studies (3/-) | 50.2 % | low | not evaluable | high | non important | - |
| Decreased appetite TRAE (grade 3-4) | 2.44 [0.57, 10.42] | | < 1 | | 0% | 4 studies (4/-) | 11.5 % | low | not evaluable | high | non important | - |
| Diarrhoea TRAE (grade 3-4) | 1.32 [0.58, 3.01] | | < 1 | | 76% | 4 studies (4/-) | 25.6 % | low | not evaluable | high | non important | - |
| Dry skin TRAE (grade 3-4) | 1.34 [0.62, 2.88] | | < 1 | | 0% | 3 studies (3/-) | 22.7 % | 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 | - |
| 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) | 3.23 [1.52, 6.88] | | < 1 | | 0% | 4 studies (4/-) | 0.1 % | 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) | 1.80 [0.42, 7.77] | | < 1 | | 0% | 4 studies (4/-) | 21.7 % | 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 | - |
| Hyperthyroidism TRAE (grade 3-4) | 2.72 [0.51, 14.70] | | < 1 | | 0% | 4 studies (4/-) | 12.3 % | low | not evaluable | 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) | 1.27 [0.21, 7.83] | | < 1 | | 0% | 4 studies (4/-) | 39.8 % | low | not evaluable | high | non important | - |
| Increase AST TRAE (grade 3-4) | 5.63 [2.53, 12.55] | | < 1 | | 0% | 4 studies (4/-) | 0.0 % | low | not evaluable | high | non important | - |
| Increased ALT TRAE (grade 3-4) | 3.93 [1.32, 11.74] | | < 1 | | 62% | 4 studies (4/-) | 0.7 % | low | not evaluable | high | non important | - |
| Increased lipase level TRAE (grade 3-4) | 2.26 [1.41, 3.63] | | < 1 | | 24% | 4 studies (4/-) | 0.0 % | low | not evaluable | high | non important | - |
| Maculopapular rash TRAE (grade 3-4) | 3.32 [1.15, 9.57] | | < 1 | | 0% | 4 studies (4/-) | 1.3 % | low | not evaluable | high | non important | - |
| Myalgia TRAE (grade 3-4) | 1.22 [0.23, 6.34] | | < 1 | | 0% | 4 studies (4/-) | 40.7 % | low | not evaluable | high | non important | - |
| Nausea TRAE (grade 3-4) | 1.87 [0.38, 9.32] | | < 1 | | 40% | 4 studies (4/-) | 22.3 % | low | not evaluable | high | 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 | - |
| Pneumonitis TRAE (grade 3-4) | 1.85 [0.55, 6.18] | | < 1 | | 0% | 4 studies (4/-) | 15.9 % | 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) | 3.36 [0.98, 11.50] | | < 1 | | 0% | 4 studies (4/-) | 2.7 % | low | not evaluable | high | non important | - |
| Pyrexia TRAE (grade 3-4) | 1.98 [0.46, 8.48] | | < 1 | | 0% | 4 studies (4/-) | 17.9 % | low | not evaluable | high | non important | - |
| Rash TRAE (grade 3-4) | 2.03 [0.45, 9.22] | | < 1 | | 59% | 4 studies (4/-) | 18.0 % | 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 | - |
| 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) | 0.85 [0.14, 5.26] | | < 1 | | 0% | 4 studies (4/-) | 56.7 % | low | not evaluable | high | non important | - |
| Vomiting TRAE (grade 3-4) | 3.76 [1.11, 12.79] | | < 1 | | 0% | 4 studies (4/-) | 1.7 % | 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) | 4.04 [1.13, 14.45] | | < 1 | | 0% | 1 study (1/-) | 1.6 % | NA | not evaluable | | non important | - |
| Asthenia AE (grade 3-4) | 0.10 [0.01, 1.78] | | < 1 | | 0% | 1 study (1/-) | 94.0 % | NA | not evaluable | | non important | - |
| Constipation AE (grade 3-4) | 0.98 [0.14, 7.01] | | < 1 | | 0% | 1 study (1/-) | 50.7 % | NA | not evaluable | | 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) | 14.32 [1.87, 109.52] | | < 1 | | 0% | 1 study (1/-) | 0.5 % | 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) | 3.90 [1.44, 10.57] | | < 1 | | 0% | 1 study (1/-) | 0.4 % | NA | not evaluable | | non important | - |
| Headache AE (grade 3-4) | 1.97 [0.18, 21.82] | | < 1 | | 0% | 1 study (1/-) | 29.2 % | NA | not evaluable | | non important | - |
| Nausea AE (grade 3-4) | 1.39 [0.61, 3.18] | | < 1 | | 0% | 1 study (1/-) | 21.7 % | NA | not evaluable | | 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) | 4.97 [0.58, 42.77] | | < 1 | | 0% | 1 study (1/-) | 7.3 % | NA | not evaluable | | non important | - |
| Pruritus AE (grade 3-4) | 5.93 [0.30, 118.96] | | < 1 | | 0% | 1 study (1/-) | 12.5 % | NA | not evaluable | | non important | - |
| Pyrexia AE (grade 3-4) | 7.94 [0.42, 150.76] | | < 1 | | 0% | 1 study (1/-) | 8.6 % | NA | not evaluable | | non important | - |
| Rash AE (grade 3-4) | 7.00 [0.86, 57.23] | | < 1 | | 0% | 1 study (1/-) | 3.6 % | NA | not evaluable | | non important | - |
| Thrombocytopenia AE (grade 3-4) | 0.03 [0.00, 0.26] | | < 1 | | 0% | 1 study (1/-) | 99.9 % | NA | not evaluable | | non important | - |
| Vomiting AE (grade 3-4) | 1.55 [0.66, 3.64] | | < 1 | | 0% | 1 study (1/-) | 15.7 % | NA | not evaluable | | non important | - |
| Weight decreased AE (grade 3-4) | 0.98 [0.06, 15.76] | | < 1 | | 0% | 1 study (1/-) | 50.5 % | NA | not evaluable | | non important | - |
