| 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) | 0.64 [0.49, 0.82] | | < 1 | | 73% | 6 studies (6/-) | 100.0 % | low | not evaluable | high | crucial | - |
| deaths (OS) (extension) | 0.63 [0.46, 0.85] | | < 1 | | 84% | 3 studies (3/-) | 99.8 % | low | not evaluable | high | important | - |
| PFS (extension) | 0.56 [0.40, 0.80] | | < 1 | | 88% | 3 studies (3/-) | 99.9 % | low | not evaluable | high | important | - |
| progression or deaths (PFS) | 0.64 [0.48, 0.86] | | < 1 | | 89% | 6 studies (6/-) | 99.8 % | 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) | 2.09 [1.23, 3.55] | | > 1 | | 90% | 6 studies (6/-) | 99.7 % | low | not evaluable | high | non important | - |
| objective responses (ORR) (extension) | 4.57 [3.31, 6.32] | | > 1 | | 50% | 3 studies (3/-) | 100.0 % | low | not evaluable | high | non important | - |
safety endpoints 00 |
| AE (any grade) | 3.12 [0.18, 53.89] | | < 1 | | 91% | 2 studies (2/-) | 21.9 % | low | not evaluable | high | non important | - |
| AE (grade 3-4) | 1.84 [0.39, 8.56] | | < 1 | | 97% | 2 studies (2/-) | 22.0 % | some concern | not evaluable | moderate | non important | - |
| AE leading to death (grade 5) | 1.29 [0.60, 2.77] | | < 1 | | 0% | 3 studies (3/-) | 26.2 % | low | not evaluable | high | non important | - |
| AE leading to treatment discontinuation (any grade) | 0.69 [0.46, 1.04] | | < 1 | | 0% | 2 studies (2/-) | 96.4 % | 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) | 0.73 [0.49, 1.10] | | < 1 | | 0% | 1 study (1/-) | 93.1 % | NA | not evaluable | | 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) | 1.37 [0.70, 2.68] | | < 1 | | 77% | 4 studies (4/-) | 18.0 % | low | not evaluable | high | non important | - |
| TRAE (grade 3-4) | 1.33 [0.50, 3.54] | | < 1 | | 96% | 4 studies (4/-) | 28.6 % | low | not evaluable | high | non important | - |
| TRAE leading to death (grade 5) | 1.00 [0.06, 15.97] | | < 1 | | 0% | 2 studies (2/-) | 50.1 % | low | not evaluable | high | non important | - |
| TRAE leading to discontinuation (any grade) | 1.87 [0.29, 12.18] | | < 1 | | 97% | 2 studies (2/-) | 25.7 % | low | not evaluable | high | non important | - |
| TRAE leading to discontinuation (grade 3-4) | 1.63 [0.17, 15.32] | | < 1 | | 98% | 2 studies (2/-) | 33.6 % | low | not evaluable | high | non important | - |
TRAE (grade 3-4) endpoints 00 |
| Abdominal pain TRAE (grade 3-4) | 0.72 [0.10, 5.18] | | < 1 | | 0% | 3 studies (3/-) | 62.9 % | low | not evaluable | high | non important | - |
| Adrenal insufficiency TRAE (grade 3-4) | 2.67 [0.70, 10.16] | | < 1 | | 0% | 2 studies (2/-) | 7.6 % | 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) | 1.52 [0.60, 3.87] | | < 1 | | 0% | 4 studies (4/-) | 19.1 % | low | not evaluable | high | non important | - |
| Asthenia TRAE (grade 3-4) | 1.19 [0.37, 3.83] | | < 1 | | 0% | 4 studies (4/-) | 38.5 % | low | not evaluable | 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 | - |
| 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) | 1.04 [0.01, 77.14] | | < 1 | | 96% | 2 studies (2/-) | 49.3 % | low | not evaluable | high | non important | - |
| Constipation TRAE (grade 3-4) | 1.00 [0.02, 50.40] | | < 1 | | 0% | 1 study (1/-) | 50.1 % | NA | not evaluable | | non important | - |
| Cough TRAE (grade 3-4) | 1.00 [0.15, 6.76] | | < 1 | | 0% | 3 studies (3/-) | 50.1 % | low | not evaluable | high | non important | - |
| Decreased appetite TRAE (grade 3-4) | 1.16 [0.23, 6.02] | | < 1 | | 0% | 4 studies (4/-) | 42.8 % | low | not evaluable | high | non important | - |
| Diarrhoea TRAE (grade 3-4) | 1.10 [0.33, 3.62] | | < 1 | | 79% | 4 studies (4/-) | 43.7 % | low | not evaluable | high | non important | - |
| Dry skin TRAE (grade 3-4) | 1.74 [0.28, 10.82] | | < 1 | | 0% | 4 studies (4/-) | 27.8 % | low | not evaluable | high | non important | - |
| Dyspnoea TRAE (grade 3-4) | 2.66 [0.40, 17.52] | | < 1 | | 0% | 2 studies (2/-) | 15.6 % | low | not evaluable | high | 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 | - |
| Fatigue TRAE (grade 3-4) | 1.99 [0.66, 6.02] | | < 1 | | 30% | 4 studies (4/-) | 11.3 % | low | not evaluable | high | non important | - |
| Headache TRAE (grade 3-4) | 1.39 [0.19, 10.03] | | < 1 | | 0% | 3 studies (3/-) | 37.4 % | low | not evaluable | high | non important | - |
| Hepatitis TRAE (grade 3-4) | 4.45 [0.43, 46.06] | | < 1 | | 0% | 2 studies (2/-) | 10.7 % | low | not evaluable | high | 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) | 3.19 [0.61, 16.63] | | < 1 | | 0% | 4 studies (4/-) | 8.5 % | low | not evaluable | high | non important | - |
| Hypophysitis TRAE (grade 3-4) | 1.00 [0.04, 24.12] | | < 1 | | 77% | 2 studies (2/-) | 50.1 % | low | not evaluable | high | non important | - |
| Hypothyroidism TRAE (grade 3-4) | 1.32 [0.15, 11.29] | | < 1 | | 0% | 3 studies (3/-) | 40.2 % | low | not evaluable | high | non important | - |
| Increase AST TRAE (grade 3-4) | 3.07 [0.94, 10.04] | | < 1 | | 26% | 3 studies (3/-) | 3.2 % | low | not evaluable | high | non important | - |
| Increased ALT TRAE (grade 3-4) | 2.40 [0.50, 11.63] | | < 1 | | 70% | 3 studies (3/-) | 13.9 % | low | not evaluable | high | non important | - |
| Increased lipase level TRAE (grade 3-4) | 1.41 [0.76, 2.62] | | < 1 | | 67% | 3 studies (3/-) | 13.5 % | 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) | 1.51 [0.91, 2.51] | | < 1 | | 0% | 4 studies (4/-) | 5.6 % | low | not evaluable | high | non important | - |
| Myalgia TRAE (grade 3-4) | 1.60 [0.36, 7.08] | | < 1 | | 0% | 4 studies (4/-) | 26.7 % | low | not evaluable | high | non important | - |
| Nausea TRAE (grade 3-4) | 0.80 [0.09, 6.69] | | < 1 | | 53% | 4 studies (4/-) | 58.3 % | 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 | - |
| 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) | 2.43 [0.53, 11.19] | | < 1 | | 0% | 3 studies (3/-) | 12.9 % | low | not evaluable | high | non important | - |
| Pruritic rash TRAE (grade 3-4) | 1.00 [0.06, 15.97] | | < 1 | | 0% | 2 studies (2/-) | 50.1 % | low | not evaluable | high | non important | - |
| Pruritus TRAE (grade 3-4) | 2.74 [0.76, 9.84] | | < 1 | | 0% | 4 studies (4/-) | 6.2 % | low | not evaluable | high | non important | - |
| Pyrexia TRAE (grade 3-4) | 1.17 [0.34, 3.98] | | < 1 | | 0% | 4 studies (4/-) | 40.4 % | low | not evaluable | high | non important | - |
| Rash TRAE (grade 3-4) | 1.29 [0.31, 5.36] | | < 1 | | 59% | 4 studies (4/-) | 36.2 % | low | not evaluable | high | 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) | 1.48 [0.11, 19.35] | | < 1 | | 0% | 2 studies (2/-) | 38.3 % | low | not evaluable | high | non important | - |
| Vitiligo TRAE (grade 3-4) | 1.00 [0.13, 7.74] | | < 1 | | 0% | 3 studies (3/-) | 50.1 % | low | not evaluable | high | non important | - |
| Vomiting TRAE (grade 3-4) | 1.29 [0.36, 4.65] | | < 1 | | 24% | 4 studies (4/-) | 34.7 % | low | not evaluable | high | non important | - |
| Weight decreased TRAE (grade 3-4) | 0.67 [0.05, 8.74] | | < 1 | | 0% | 2 studies (2/-) | 61.9 % | 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 | - |
| 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) | 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 | - |
