| 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) | 0.67 [0.56, 0.80] | | < 1 | | 42% | 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) | 0.61 [0.42, 0.89] | | < 1 | | 87% | 5 studies (5/-) | 99.5 % | low | not evaluable | high | important | - |
| DCR | 0.91 [0.63, 1.32] | | > 1 | | 0% | 1 study (1/-) | 31.6 % | NA | not evaluable | | non important | - |
| objective responses (ORR) | 3.28 [1.32, 8.18] | | > 1 | | 95% | 5 studies (5/-) | 99.5 % | 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) | 14.27 [3.34, 61.03] | | < 1 | | 0% | 1 study (1/-) | 0.0 % | NA | not evaluable | | non important | - |
| AE (grade 3-4) | 4.03 [2.70, 6.00] | | < 1 | | 0% | 1 study (1/-) | 0.0 % | NA | not evaluable | | non important | - |
| AE leading to death (grade 5) | 1.39 [0.43, 4.44] | | < 1 | | 0% | 1 study (1/-) | 29.1 % | 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) | 1.00 [0.10, 9.59] | | < 1 | | 0% | 3 studies (3/-) | 50.1 % | low | not evaluable | high | 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) | 1.98 [0.57, 6.89] | | < 1 | | 30% | 4 studies (4/-) | 14.3 % | 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 | - |
| 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) | 5.06 [1.06, 24.09] | | < 1 | | 0% | 4 studies (4/-) | 2.1 % | low | not evaluable | 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 | - |
| 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) | 0.98 [0.14, 7.03] | | < 1 | | 0% | 1 study (1/-) | 50.7 % | NA | not evaluable | | 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) | 1.74 [0.50, 6.04] | | < 1 | | 0% | 1 study (1/-) | 19.1 % | NA | not evaluable | | non important | - |
| Constipation AE (grade 3-4) | 0.98 [0.02, 49.71] | | < 1 | | 0% | 1 study (1/-) | 50.4 % | NA | not evaluable | | non important | - |
| Decreased appetite AE (grade 3-4) | 1.97 [0.07, 58.97] | | < 1 | | 0% | 1 study (1/-) | 35.0 % | NA | not evaluable | | 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 | - |
| Fatigue AE (grade 3-4) | 1.65 [0.39, 7.00] | | < 1 | | 0% | 1 study (1/-) | 24.9 % | NA | not evaluable | | non important | - |
| Headache AE (grade 3-4) | 1.97 [0.07, 58.97] | | < 1 | | 0% | 1 study (1/-) | 35.0 % | NA | not evaluable | | 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 | - |
| 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) | 10.02 [0.54, 184.60] | | < 1 | | 0% | 1 study (1/-) | 6.3 % | NA | not evaluable | | non important | - |
| Peripheral oedema AE (grade 3-4) | 0.98 [0.06, 15.80] | | < 1 | | 0% | 1 study (1/-) | 50.5 % | NA | not evaluable | | non important | - |
| Pruritus AE (grade 3-4) | 0.98 [0.02, 49.71] | | < 1 | | 0% | 1 study (1/-) | 50.4 % | NA | not evaluable | | non important | - |
| Pyrexia AE (grade 3-4) | 6.03 [0.72, 50.50] | | < 1 | | 0% | 1 study (1/-) | 5.0 % | NA | not evaluable | | non important | - |
| Rash AE (grade 3-4) | 7.83 [1.77, 34.66] | | < 1 | | 0% | 1 study (1/-) | 0.3 % | NA | not evaluable | | non important | - |
| Rash maculopapular AE (grade 3-4) | 7.98 [0.42, 151.89] | | < 1 | | 0% | 1 study (1/-) | 8.6 % | NA | not evaluable | | non important | - |
| Sepsis AE (grade 3-4) | 12.08 [0.67, 217.70] | | < 1 | | 0% | 1 study (1/-) | 4.7 % | NA | not evaluable | | non important | - |
| Vomiting AE (grade 3-4) | 2.49 [0.48, 12.97] | | < 1 | | 0% | 1 study (1/-) | 14.0 % | NA | not evaluable | | non important | - |
