Table 3 Summary results of the all-grade and grade ≥ 3 adverse events (AEs) in combination therapies
adverse events | All-grade | Grade ≥ 3 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
No. of Studies | No. of Patients | model | Event rate with 95% CI | Z value | p value | No. of Studies | No. of Patients | model | Event rate with 95% CI | Z value | p value | |
Hematologic | ||||||||||||
 Anaemia | 2 | 53 | Random | 0.687 (0.017–0.996) | 0.319 | 0.750 |  |  |  |  |  |  |
 Lymphopenia | 2 | 119 | Random | 0.619 (0.007–0.997) | 0.176 | 0.861 | 2 | 119 | Random | 0.568 (0.004–0.998) | 0.092 | 0.927 |
 Thrombocytopenia | 3 | 143 | Random | 0.248 (0.006–0.951) | −0.534 | 0.593 |  |  |  |  |  |  |
 Neutropenia | 2 | 42 | Random | 0.812 (0.035–0.998) | 0.600 | 0.549 |  |  |  |  |  |  |
Gastrointestinal disorders | ||||||||||||
 Gastrointestinal disorder | 2 | 53 | Random | 0.599 (0.001–0.999) | 0.112 | 0.911 |  |  |  |  |  |  |
 Nausea | 3 | 127 | Random | 0.159 (0.046–0.425) | −2.393 | 0.017 |  |  |  |  |  |  |
 Vomiting | 3 | 127 | Random | 0.093 (0.032–0.242) | −3.945 | 0.000 |  |  |  |  |  |  |
 Diarrhea | 2 | 103 | Fixed | 0.148 (0.091–0.231) | −6.240 | 0.000 |  |  |  |  |  |  |
 Stomatitis | 3 | 143 | Random | 0.185 (0.035–0.585) | −1.592 | 0.111 | 2 | 119 | Random | 0.046 (0.004–0.393) | −2.290 | 0.022 |
General disorders | ||||||||||||
 Fatigue | 3 | 127 | Random | 0.278 (0.072–0.659) | −1.159 | 0.246 |  |  |  |  |  |  |
 Pyrexia | 3 | 143 | Random | 0.234 (0.017–0.844) | −0.810 | 0.418 |  |  |  |  |  |  |
 Chills | 2 | 37 | Fixed | 0.110 (0.042–0.260) | − 3.930 | 0.000 |  |  |  |  |  |  |
 Oedema peripheral | 2 | 37 | Fixed | 0.056 (0.014–0.200) | −3.863 | 0.000 |  |  |  |  |  |  |
Injury, poisoning and procedural complications | ||||||||||||
 Infusion related reaction | 2 | 37 | Fixed | 0.110 (0.042–0.260) | −3.930 | 0.000 |  |  |  |  |  |  |
Metabolism and nutrition disorders /investigations | ||||||||||||
 AST increased | 2 | 119 | Random | 0.163 (0.036–0.501) | −1.956 | 0.050 | 2 | 119 | Fixed | 0.059 (0.028–0.119 | −7.103 | 0.000 |
 ALT increased | 2 | 119 | Random | 0.197 (0.030–0.663) | −1.325 | 0.185 | 2 | 119 | Fixed | 0.044 (0.019–0.102) | −6.696 | 0.000 |
 Hyponatraemia | 2 | 119 | Random | 0.060 (0.009–0.301) | −2.825 | 0.005 | 2 | 119 | Random | 0.032 (0.005–0.170) | −3.659 | 0.000 |
 Hyperuricaemia | 2 | 37 | Fixed | 0.056 (0.014–0.200) | −3.863 | 0.000 |  |  |  |  |  |  |
 Hypomagnesaemia | 2 | 37 | Fixed | 0.056 (0.014–0.200) | −3.863 | 0.000 |  |  |  |  |  |  |
 Hypophosphataemia | 2 | 53 | Fixed | 0.116 (0.053–0.236) | − 4.663 | 0.000 |  |  |  |  |  |  |
 Weight decreased | 2 | 37 | Fixed | 0.113 (0.043–0.265) | − 3.878 | 0.000 |  |  |  |  |  |  |
 Platelet count decreased | 2 | 103 | Fixed | 0.050 (0.021–0.114) | −6.436 | 0.000 |  |  |  |  |  |  |
 Decreased appetite | 3 | 143 | Random | 0.275 (0.031–0.817) | −0.769 | 0.442 |  |  |  |  |  |  |
 Dehydration | 2 | 37 | Fixed | 0.204 (0.099–0.373) | −3.166 | 0.002 |  |  |  |  |  |  |
 Hypotension | 2 | 114 | Fixed | 0.021 (0.005–0.082) | −5.334 | 0.000 |  |  |  |  |  |  |
Musculoskeletal and connective tissue disorders | ||||||||||||
 Arthralgia | 2 | 37 | Fixed | 0.113 (0.043–0.265) | −3.878 | 0.000 |  |  |  |  |  |  |
 Musculoskeletal chest pain | 2 | 37 | Fixed | 0.056 (0.014–0.200) | −3.863 | 0.000 |  |  |  |  |  |  |
 Myalgia | 3 | 127 | Fixed | 0.041 (0.017–0.095) | −6.889 | 0.000 |  |  |  |  |  |  |
 Abdominal pain | 2 | 37 | Fixed | 0.081 (0.026–0.223) | − 4.029 | 0.000 |  |  |  |  |  |  |
 Neck pain | 2 | 37 | Fixed | 0.081 (0.026–0.223) | −4.029 | 0.000 |  |  |  |  |  |  |
 Back pain | 2 | 37 | Fixed | 0.056 (0.014–0.200) | −3.863 | 0.000 |  |  |  |  |  |  |
 Chest pain | 2 | 37 | Fixed | 0.056 (0.014–0.200) | − 3.863 | 0.000 |  |  |  |  |  |  |
Skin and subcutaneous tissue disorders | ||||||||||||
 Rash | 2 | 114 | Fixed | 0.370 (0.286–0.462) | −2.741 | 0.006 |  |  |  |  |  |  |
 Rash maculo-papular | 2 | 114 | Fixed | 0.182 (0.121–0.266) | −6.046 | 0.000 |  |  |  |  |  |  |
 Skin exfoliation | 2 | 114 | Fixed | 0.035 (0.013–0.090) | − 6.501 | 0.000 |  |  |  |  |  |  |
 Dry skin | 2 | 114 | Fixed | 0.070 (0.036–0.135) | −7.033 | 0.000 |  |  |  |  |  |  |
Infections and infestations | ||||||||||||
 Sepsis | 2 | 37 | Random | 0.139 (0.017–0.607) | −1.584 | 0.113 |  |  |  |  |  |  |
 Pneumonia | 2 | 53 | Fixed | 0.116 (0.053–0.236) | −4.663 | 0.000 |  |  |  |  |  |  |
 Pneumonitis | 2 | 114 | Fixed | 0.021 (0.005–0.082) | −5.334 | 0.000 |  |  |  |  |  |  |
 Urinary tract infection | 2 | 37 | Fixed | 0.056 (0.014–0.200) | −3.863 | 0.000 |  |  |  |  |  |  |
Nervous system and psychiatric disorders | ||||||||||||
 Dysgeusia | 2 | 114 | Fixed | 0.044 (0.018–0.101) | −6.738 | 0.000 |  |  |  |  |  |  |
 Headache | 2 | 37 | Fixed | 0.142 (0.060–0.300) | −3.712 | 0.000 |  |  |  |  |  |  |
 Insomnia | 2 | 37 | Fixed | 0.110 (0.042–0.260) | −3.930 | 0.000 |  |  |  |  |  |  |
 Malaise | 2 | 114 | Fixed | 0.048 (0.020–0.110) | −6.509 | 0.000 |  |  |  |  |  |  |