| 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) | 0.88 [0.81, 0.97] | | < 1 | | 0% | 5 studies (5/-) | 99.6 % | low | not evaluable | high | crucial | - |
| deaths (OS) (extension) | 0.24 [0.03, 2.28] | | < 1 | | 0% | 1 study (1/-) | 89.2 % | NA | not evaluable | | important | - |
| PFS (extension) | 0.80 [0.69, 0.92] | | < 1 | | 0% | 1 study (1/-) | 99.9 % | NA | not evaluable | | important | - |
| progression or deaths (PFS) | 0.92 [0.64, 1.31] | | < 1 | | 93% | 4 studies (4/-) | 68.1 % | low | not evaluable | high | important | - |
| DCR | 0.60 [0.39, 0.94] | | > 1 | | 0% | 1 study (1/-) | 1.3 % | NA | not evaluable | | non important | - |
| DOR | 0.78 [0.63, 0.97] | | < 1 | | 0% | 1 study (1/-) | 98.6 % | NA | not evaluable | | non important | - |
| events or deaths (EFS) | 0.66 [0.48, 0.92] | | < 1 | | 0% | 2 studies (2/-) | 99.3 % | low | not evaluable | high | non important | - |
| objective responses (ORR) | 0.85 [0.31, 2.31] | | > 1 | | 97% | 4 studies (4/-) | 37.2 % | low | not evaluable | high | non important | - |
| pCR | 3.30 [0.99, 11.04] | | > 1 | | 93% | 3 studies (3/-) | 97.4 % | low | not evaluable | high | non important | - |
safety endpoints 00 |
| AE (any grade) | 1.47 [0.63, 3.40] | | < 1 | | 5% | 4 studies (4/-) | 18.6 % | low | not evaluable | high | non important | - |
| AE (grade 3-4) | 1.28 [1.09, 1.50] | | < 1 | | 0% | 4 studies (4/-) | 0.1 % | low | not evaluable | high | non important | - |
| AE leading to death (grade 5) | 1.61 [0.49, 5.27] | | < 1 | | 0% | 3 studies (3/-) | 21.7 % | low | not evaluable | high | non important | - |
| AE leading to treatment discontinuation (any grade) | 1.66 [0.89, 3.11] | | < 1 | | 71% | 2 studies (2/-) | 5.6 % | low | not evaluable | high | non important | - |
| SAE (any grade) | 1.25 [0.91, 1.70] | | < 1 | | 48% | 4 studies (4/-) | 8.1 % | low | not evaluable | high | non important | - |
| STRAE (any grade) | 1.72 [1.21, 2.45] | | < 1 | | 0% | 2 studies (2/-) | 0.1 % | low | not evaluable | high | non important | - |
| TRAE (any grade) | 1.38 [0.84, 2.27] | | < 1 | | 11% | 4 studies (4/-) | 10.3 % | low | not evaluable | high | non important | - |
| TRAE (grade 3-4) | 0.93 [0.56, 1.56] | | < 1 | | 92% | 5 studies (5/-) | 60.3 % | low | not evaluable | high | non important | - |
| TRAE leading to death (grade 5) | 1.13 [0.51, 2.49] | | < 1 | | 0% | 4 studies (4/-) | 38.0 % | some concern | not evaluable | moderate | non important | - |
| TRAE leading to discontinuation (any grade) | 1.72 [0.89, 3.31] | | < 1 | | 52% | 2 studies (2/-) | 5.4 % | low | not evaluable | high | non important | - |
TRAE (grade 3-4) endpoints 00 |
| Abdominal pain TRAE (grade 3-4) | 0.94 [0.06, 15.18] | | < 1 | | 0% | 1 study (1/-) | 51.6 % | NA | not evaluable | | non important | - |
| Acute kidney injury TRAE (grade 3-4) | 0.47 [0.02, 14.11] | | < 1 | | 0% | 1 study (1/-) | 66.5 % | NA | not evaluable | | non important | - |
| Adrenal insufficiency TRAE (grade 3-4) | 3.47 [0.52, 23.34] | | < 1 | | 0% | 3 studies (3/-) | 10.2 % | low | not evaluable | high | non important | - |
| Alopecia TRAE (grade 3-4) | 0.86 [0.41, 1.80] | | < 1 | | 0% | 3 studies (3/-) | 65.4 % | low | not evaluable | high | non important | - |
| Anaemia TRAE (grade 3-4) | 1.03 [0.65, 1.65] | | < 1 | | 60% | 3 studies (3/-) | 44.8 % | low | not evaluable | high | non important | - |
| Asthenia TRAE (grade 3-4) | 1.37 [0.69, 2.72] | | < 1 | | 0% | 2 studies (2/-) | 18.6 % | low | not evaluable | high | non important | - |
| Colitis TRAE (grade 3-4) | 2.02 [0.49, 8.26] | | < 1 | | 0% | 4 studies (4/-) | 16.5 % | low | not evaluable | high | non important | - |
| Constipation TRAE (grade 3-4) | 0.48 [0.04, 6.30] | | < 1 | | 0% | 2 studies (2/-) | 70.9 % | some concern | not evaluable | moderate | non important | - |
| Cough TRAE (grade 3-4) | 1.89 [0.06, 56.64] | | < 1 | | 0% | 1 study (1/-) | 35.8 % | NA | not evaluable | | non important | - |
| Decreased appetite TRAE (grade 3-4) | 2.02 [0.34, 12.03] | | < 1 | | 0% | 2 studies (2/-) | 22.2 % | low | not evaluable | high | non important | - |
| Diabetes TRAE (grade 3-4) | 1.25 [0.20, 7.77] | | < 1 | | 0% | 3 studies (3/-) | 40.7 % | low | not evaluable | high | non important | - |
| Diarrhoea TRAE (grade 3-4) | 0.69 [0.10, 4.85] | | < 1 | | 78% | 2 studies (2/-) | 64.5 % | low | not evaluable | high | non important | - |
| Dysgeusia TRAE (grade 3-4) | 0.50 [0.01, 25.13] | | < 1 | | 0% | 1 study (1/-) | 63.4 % | NA | not evaluable | | non important | - |
| Dyspnoea TRAE (grade 3-4) | 1.89 [0.06, 56.64] | | < 1 | | 0% | 1 study (1/-) | 35.8 % | NA | not evaluable | | non important | - |
| Fatigue TRAE (grade 3-4) | 1.51 [0.84, 2.72] | | < 1 | | 0% | 3 studies (3/-) | 8.6 % | low | not evaluable | high | non important | - |
| Febrile neutropenia TRAE (grade 3-4) | 0.31 [0.01, 6.85] | | < 1 | | 79% | 2 studies (2/-) | 76.6 % | low | not evaluable | high | non important | - |
| Guillain-Barré syndrome TRAE (grade 3-4) | 0.51 [0.02, 15.24] | | < 1 | | 0% | 1 study (1/-) | 65.0 % | NA | not evaluable | | non important | - |
| Headache TRAE (grade 3-4) | 1.89 [0.06, 56.64] | | < 1 | | 0% | 1 study (1/-) | 35.8 % | NA | not evaluable | | non important | - |
| Hepatitis TRAE (grade 3-4) | 4.26 [0.42, 42.77] | | < 1 | | 0% | 2 studies (2/-) | 11.1 % | low | not evaluable | high | non important | - |
| Hyperthyroidism TRAE (grade 3-4) | 1.24 [0.21, 7.26] | | < 1 | | 0% | 4 studies (4/-) | 40.6 % | low | not evaluable | high | non important | - |
| Hypophysitis TRAE (grade 3-4) | 8.04 [0.46, 140.38] | | < 1 | | 0% | 1 study (1/-) | 7.9 % | NA | not evaluable | | non important | - |
| Hypothyroidism TRAE (grade 3-4) | 1.98 [0.38, 10.33] | | < 1 | | 0% | 4 studies (4/-) | 20.9 % | low | not evaluable | high | non important | - |
| Increase AST TRAE (grade 3-4) | 3.49 [0.75, 16.21] | | < 1 | | 45% | 2 studies (2/-) | 5.6 % | some concern | not evaluable | moderate | non important | - |
| Increased ALT TRAE (grade 3-4) | 1.69 [1.05, 2.73] | | < 1 | | 0% | 3 studies (3/-) | 1.6 % | low | not evaluable | high | non important | - |
| Infusion-related reactions TRAE (grade 3-4) | 2.24 [0.82, 6.15] | | < 1 | | 0% | 2 studies (2/-) | 5.8 % | low | not evaluable | high | non important | - |
| Leucopenia TRAE (grade 3-4) | 0.78 [0.61, 1.00] | | < 1 | | 8% | 3 studies (3/-) | 97.5 % | low | not evaluable | high | non important | - |
| Maculopapular rash TRAE (grade 3-4) | 1.89 [0.06, 56.64] | | < 1 | | 0% | 1 study (1/-) | 35.8 % | NA | not evaluable | | non important | - |
| Myalgia TRAE (grade 3-4) | 0.47 [0.02, 14.11] | | < 1 | | 0% | 1 study (1/-) | 66.5 % | NA | not evaluable | | non important | - |
| Myocarditis TRAE (grade 3-4) | 1.99 [0.09, 44.34] | | < 1 | | 0% | 1 study (1/-) | 33.3 % | NA | not evaluable | | non important | - |
| Myositis TRAE (grade 3-4) | 2.23 [0.32, 15.67] | | < 1 | | 0% | 3 studies (3/-) | 21.2 % | low | not evaluable | high | non important | - |
| Nausea TRAE (grade 3-4) | 1.77 [0.85, 3.67] | | < 1 | | 0% | 3 studies (3/-) | 6.4 % | low | not evaluable | high | non important | - |
| Nephritis TRAE (grade 3-4) | 3.49 [0.34, 35.41] | | < 1 | | 0% | 2 studies (2/-) | 14.7 % | low | not evaluable | high | non important | - |
| Neutropenia TRAE (grade 3-4) | 0.81 [0.42, 1.55] | | < 1 | | 83% | 3 studies (3/-) | 74.1 % | low | not evaluable | high | non important | - |
| Palmar-plantar erythrodysaesthesia syndrome TRAE (grade 3-4) | 0.13 [0.02, 1.08] | | < 1 | | 0% | 1 study (1/-) | 97.0 % | NA | not evaluable | | non important | - |
| Pancreatitis TRAE (grade 3-4) | 4.00 [0.21, 75.85] | | < 1 | | 0% | 1 study (1/-) | 18.1 % | NA | not evaluable | | non important | - |
| Pancytopenia TRAE (grade 3-4) | 0.24 [0.01, 5.23] | | < 1 | | 0% | 1 study (1/-) | 81.7 % | NA | not evaluable | | non important | - |
| Peripheral neuropathy TRAE (grade 3-4) | 1.88 [0.62, 5.72] | | < 1 | | 0% | 1 study (1/-) | 13.2 % | NA | not evaluable | | non important | - |
| Peripheral sensory neuropathy TRAE (grade 3-4) | 0.72 [0.13, 4.06] | | < 1 | | 37% | 2 studies (2/-) | 64.7 % | low | not evaluable | high | non important | - |
| Pneumonia TRAE (grade 3-4) | 0.24 [0.01, 5.23] | | < 1 | | 0% | 1 study (1/-) | 81.7 % | NA | not evaluable | | non important | - |
| Pneumonitis TRAE (grade 3-4) | 2.93 [0.72, 11.83] | | < 1 | | 0% | 4 studies (4/-) | 6.7 % | low | not evaluable | high | non important | - |
| Pruritus TRAE (grade 3-4) | 1.89 [0.06, 56.64] | | < 1 | | 0% | 1 study (1/-) | 35.8 % | NA | not evaluable | | non important | - |
| Pyrexia TRAE (grade 3-4) | 2.39 [0.45, 12.62] | | < 1 | | 0% | 2 studies (2/-) | 15.4 % | low | not evaluable | high | non important | - |
| Rash TRAE (grade 3-4) | 1.37 [0.49, 3.84] | | < 1 | | 2% | 2 studies (2/-) | 27.6 % | low | not evaluable | high | non important | - |
| Sarcoidosis TRAE (grade 3-4) | 0.50 [0.01, 25.13] | | < 1 | | 0% | 1 study (1/-) | 63.4 % | NA | not evaluable | | non important | - |
| Sepsis TRAE (grade 3-4) | 0.94 [0.02, 47.78] | | < 1 | | 0% | 1 study (1/-) | 51.1 % | NA | not evaluable | | non important | - |
| Severe skin reaction TRAE (grade 3-4) | 5.90 [1.64, 21.16] | | < 1 | | 0% | 4 studies (4/-) | 0.3 % | low | not evaluable | high | non important | - |
| Stomatitis TRAE (grade 3-4) | 2.64 [0.12, 57.65] | | < 1 | | 49% | 2 studies (2/-) | 27.1 % | low | not evaluable | high | non important | - |
| Thrombocytopenia TRAE (grade 3-4) | 0.94 [0.06, 15.18] | | < 1 | | 0% | 1 study (1/-) | 51.6 % | NA | not evaluable | | non important | - |
| Thyroiditis TRAE (grade 3-4) | 1.50 [0.13, 17.05] | | < 1 | | 0% | 2 studies (2/-) | 37.4 % | low | not evaluable | high | non important | - |
| Urticaria TRAE (grade 3-4) | 1.89 [0.06, 56.64] | | < 1 | | 0% | 1 study (1/-) | 35.8 % | NA | not evaluable | | non important | - |
| Uveitis TRAE (grade 3-4) | 0.50 [0.01, 25.13] | | < 1 | | 0% | 1 study (1/-) | 63.4 % | NA | not evaluable | | non important | - |
| Vomiting TRAE (grade 3-4) | 1.51 [0.59, 3.82] | | < 1 | | 0% | 1 study (1/-) | 19.5 % | NA | not evaluable | | non important | - |
| Weight decreased TRAE (grade 3-4) | 0.47 [0.04, 5.22] | | < 1 | | 0% | 1 study (1/-) | 72.9 % | NA | not evaluable | | non important | - |
AE (grade 3-4) endpoints 00 |
| hepatitis (Autoimmune) AE (grade 3-4) | 1.23 [0.14, 10.62] | | < 1 | | 0% | 2 studies (2/-) | 42.4 % | low | not evaluable | high | non important | - |
| Abdominal pain AE (grade 3-4) | 1.16 [0.20, 6.72] | | < 1 | | 0% | 3 studies (3/-) | 43.5 % | low | not evaluable | high | non important | - |
| Acute kidney injury AE (grade 3-4) | 1.93 [0.06, 57.72] | | < 1 | | 0% | 1 study (1/-) | 35.4 % | NA | not evaluable | | non important | - |
| Adrenal insufficiency AE (grade 3-4) | 1.93 [0.06, 57.72] | | < 1 | | 0% | 1 study (1/-) | 35.4 % | NA | not evaluable | | non important | - |
| Alopecia AE (grade 3-4) | 1.43 [0.23, 8.79] | | < 1 | | 0% | 3 studies (3/-) | 35.1 % | low | not evaluable | high | non important | - |
| Anaemia AE (grade 3-4) | 1.10 [0.64, 1.87] | | < 1 | | 0% | 3 studies (3/-) | 36.6 % | low | not evaluable | high | non important | - |
| Arthralgia AE (grade 3-4) | 1.30 [0.25, 6.81] | | < 1 | | 0% | 3 studies (3/-) | 37.7 % | low | not evaluable | high | non important | - |
| Asthenia AE (grade 3-4) | 0.98 [0.31, 3.12] | | < 1 | | 0% | 2 studies (2/-) | 51.1 % | low | not evaluable | high | non important | - |
| Back pain AE (grade 3-4) | 1.90 [0.49, 7.43] | | < 1 | | 0% | 3 studies (3/-) | 17.8 % | low | not evaluable | high | non important | - |
| Blood creatinine increased AE (grade 3-4) | 0.05 [0.00, 0.89] | | < 1 | | 0% | 1 study (1/-) | 97.8 % | NA | not evaluable | | non important | - |
| Cardiomyopathy AE (grade 3-4) | 1.93 [0.06, 57.72] | | < 1 | | 0% | 1 study (1/-) | 35.4 % | NA | not evaluable | | non important | - |
| Chills AE (grade 3-4) | 1.93 [0.06, 57.72] | | < 1 | | 0% | 1 study (1/-) | 35.4 % | NA | not evaluable | | non important | - |
| Colitis AE (grade 3-4) | 0.96 [0.06, 15.47] | | < 1 | | 0% | 1 study (1/-) | 51.0 % | NA | not evaluable | | non important | - |
| Constipation AE (grade 3-4) | 1.39 [0.29, 6.62] | | < 1 | | 0% | 3 studies (3/-) | 34.1 % | low | not evaluable | high | non important | - |
| Cough AE (grade 3-4) | 0.96 [0.10, 9.23] | | < 1 | | 0% | 3 studies (3/-) | 51.5 % | low | not evaluable | high | non important | - |
| Decreased appetite AE (grade 3-4) | 0.97 [0.22, 4.30] | | < 1 | | 0% | 2 studies (2/-) | 51.5 % | low | not evaluable | high | non important | - |
| Diarrhoea AE (grade 3-4) | 1.58 [0.48, 5.16] | | < 1 | | 25% | 3 studies (3/-) | 22.5 % | low | not evaluable | high | non important | - |
| Dizziness AE (grade 3-4) | 0.96 [0.02, 48.73] | | < 1 | | 0% | 1 study (1/-) | 50.7 % | NA | not evaluable | | non important | - |
| Dry skin AE (grade 3-4) | 1.43 [0.11, 18.75] | | < 1 | | 0% | 2 studies (2/-) | 39.3 % | low | not evaluable | high | non important | - |
| Dysgeusia AE (grade 3-4) | 0.99 [0.06, 15.89] | | < 1 | | 0% | 2 studies (2/-) | 50.2 % | low | not evaluable | high | non important | - |
| Dyspepsia AE (grade 3-4) | 1.02 [0.02, 51.63] | | < 1 | | 0% | 1 study (1/-) | 49.6 % | NA | not evaluable | | non important | - |
| Dysphonia AE (grade 3-4) | 1.93 [0.06, 57.72] | | < 1 | | 0% | 1 study (1/-) | 35.4 % | NA | not evaluable | | non important | - |
| Dyspnoea AE (grade 3-4) | 0.98 [0.30, 3.20] | | < 1 | | 0% | 3 studies (3/-) | 51.6 % | low | not evaluable | high | non important | - |
| Epistaxis AE (grade 3-4) | 0.95 [0.06, 15.32] | | < 1 | | 0% | 2 studies (2/-) | 51.4 % | low | not evaluable | high | non important | - |
| Fatigue AE (grade 3-4) | 0.93 [0.54, 1.59] | | < 1 | | 0% | 3 studies (3/-) | 60.9 % | low | not evaluable | high | non important | - |
| Febrile neutropenia AE (grade 3-4) | 1.32 [0.68, 2.57] | | < 1 | | 0% | 2 studies (2/-) | 20.6 % | low | not evaluable | high | non important | - |
| Headache AE (grade 3-4) | 0.60 [0.15, 2.42] | | < 1 | | 0% | 3 studies (3/-) | 76.1 % | low | not evaluable | high | non important | - |
| Hypertension AE (grade 3-4) | 0.59 [0.25, 1.38] | | < 1 | | 31% | 2 studies (2/-) | 89.0 % | low | not evaluable | high | non important | - |
