Table 2.
Any grade | Grade ≥3 | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
AEs | Treatment | Included study | Event | Total patients | Pooled rate (95%Cl) | Model | P-value | Included study | Event | Total patients | Pooled rate (95%Cl) | Model | P-value |
GENERAL | |||||||||||||
Fatigue | Nivolumab | 4 | 40 | 202 | 0.2018 [0.1514; 0.2636] | Fixed | 0.007 | 4 | 0 | 202 | 0.0121 [0.0030; 0.0471] | Fixed | 0.2200 |
Pembrolizumab | 4 | 28 | 284 | 0.1024 [0.0715; 0.1445] | Fixed | 3 | 3 | 253 | 0.0280 [0.0044; 0.1595] | Random | |||
Overall | 8 | 68 | 486 | 0.1491 [0.1027; 0.2113] | Random | 7 | 3 | 455 | 0.0245 [0.0113; 0.0524] | Fixed | |||
Pyrexia | Nivolumab | 3 | 16 | 122 | 0.1675 [0.0486; 0.4422] | Random | 0.442 | 3 | 1 | 122 | 0.0367 [0.0105; 0.1199] | Fixed | 0.49 |
Pembrolizumab | 3 | 26 | 253 | 0.1030 [0.0711; 0.1471] | Fixed | 3 | 2 | 253 | 0.0208 [0.0073; 0.0579] | Fixed | |||
Overall | 6 | 42 | 375 | 0.1300 [0.0728; 0.2213] | Random | 6 | 3 | 375 | 0.0263 [0.0118; 0.0575] | Fixed | |||
Chills | Pembrolizumab | 3 | 9 | 266 | 0.0386 [0.0202; 0.0727] | Fixed | 2 | 0 | 235 | 0.0067 [0.0009; 0.0463] | Fixed | ||
Asthenia | Pembrolizumab | 2 | 5 | 241 | 0.0288 [0.0064; 0.1199] | Random | 1 | 1 | 33 | 0.0303 | |||
RESPIRATORY | |||||||||||||
Pneumonitis | Nivolumab | 2 | 12 | 162 | 0.0629 [0.0129; 0.2571] | Random | 0.859 | 2 | 5 | 162 | 0.0370 [0.0155; 0.0860] | Fixed | 0.853 |
Pembrolizumab | 2 | 4 | 49 | 0.0840 [0.0319; 0.2037] | Fixed | 1 | 1 | 33 | 0.0303 | ||||
Overall | 4 | 15 | 211 | 0.0942 [0.0574; 0.1508] | Fixed | 3 | 6 | 195 | 0.0358 [0.0161; 0.0775] | Fixed | |||
Embolism | Nivolumab | 2 | 1 | 162 | 0.0138 [0.0035; 0.0535] | Fixed | 2 | 1 | 162 | 0.0138 [0.0035; 0.0535] | Fixed | ||
Cough | Nivolumab | 1 | 2 | 23 | 0.0879 | 1 | 0 | 23 | 0 | ||||
Pembrolizumab | 2 | 19 | 235 | 0.1297 [0.0236; 0.4793] | Random | 2 | 1 | 235 | 0.0091 [0.0023; 0.0357] | Fixed | |||
Overall | 3 | 21 | 258 | 0.1156 [0.0346; 0.3226] | Random | 3 | 1 | 258 | 0.0107 [0.0031; 0.0364] | Fixed | |||
Upper respiratory tract infection | Nivolumab | 2 | 5 | 97 | 0.0603 [0.0010; 0.8038] | Random | 2 | 0 | 97 | 0.0130 [0.0018; 0.0871] | Fixed | ||
Pembrolizumab | 1 | 13 | 210 | 0.0619 | 1 | 0 | 210 | 0 | |||||
Overall | 3 | 18 | 307 | 0.0780 [0.0147; 0.3243] | Random | 3 | 0 | 307 | 0.0074 [0.0015; 0.0358] | Fixed | |||
Dyspnea | Nivolumab | 1 | 3 | 80 | 0.0375 | 1 | 1 | 80 | 0.0125 | ||||
Pembrolizumab | 3 | 17 | 266 | 0.0951 [0.0172; 0.3873] | Random | 2 | 6 | 235 | 0.0424 [0.0024; 0.4524] | Random | |||
Overall | 4 | 20 | 346 | 0.0764 [0.0202; 0.2489] | Random | 3 | 7 | 315 | 0.0298 [0.0036; 0.2068] | Random | |||
SKIN | |||||||||||||
Rash | Nivolumab | 4 | 35 | 202 | 0.1927 [0.1146; 0.3057] | Random | 0.008 | 4 | 5 | 202 | 0.0366 [0.0175; 0.0749] | Fixed | 0.651 |
Pembrolizumab | 2 | 18 | 235 | 0.0766 [0.0488; 0.1183] | Fixed | 2 | 1 | 235 | 0.0145 [0.0006; 0.2577] | Random | |||
Overall | 6 | 53 | 437 | 0.1480 [0.0869; 0.2408] | Random | 6 | 6 | 437 | 0.0338 [0.0176; 0.0639] | Fixed | |||
Pruritus | Nivolumab | 4 | 24 | 202 | 0.1403 [0.0707; 0.2593] | Random | 4 | 0 | 202 | 0.0121 [0.0030; 0.0471] | Fixed | ||
Pembrolizumab | 1 | 8 | 210 | 0.0381 | 1 | 0 | 210 | 0 | |||||
Overall | 5 | 32 | 412 | 0.1081 [0.0509; 0.2152] | Random | 5 | 0 | 412 | 0.0087 [0.0025; 0.0296] | Fixed | |||
GASTROINTESTINAL | |||||||||||||
Decreased appetite | Nivolumab | 2 | 9 | 162 | 0.0532 [0.0160; 0.1621] | Random | 0.645 | 2 | 0 | 162 | 0.0061 [0.0009; 0.0420] | Fixed | |
Pembrolizumab | 2 | 4 | 49 | 0.0844 [0.0320; 0.2045] | Fixed | 1 | 0 | 18 | 0 | ||||
Overall | 4 | 13 | 211 | 0.0701 [0.0410; 0.1172] | Fixed | 3 | 0 | 180 | 0.0099 [0.0020; 0.0476] | Fixed | |||
Diarrhea | Nivolumab | 4 | 19 | 202 | 0.0959 [0.0620; 0.1455] | Fixed | 0.9710 | 4 | 0 | 202 | 0.0121 [0.0030; 0.0471] | Fixed | 0.853 |
Pembrolizumab | 4 | 26 | 284 | 0.0969 [0.0667; 0.1387] | Fixed | 3 | 2 | 253 | 0.0142 [0.0050; 0.0398] | Fixed | |||
Overall | 8 | 45 | 486 | 0.0965 [0.0727; 0.1269] | Fixed | 7 | 2 | 455 | 0.0134 [0.0058; 0.0306] | Fixed | |||
Nausea | Nivolumab | 2 | 13 | 103 | 0.1262 [0.0747; 0.2054] | Fixed | 0.305 | 2 | 0 | 103 | 0.0113 [0.0016; 0.0761] | Fixed | 0.958 |
Pembrolizumab | 4 | 23 | 284 | 0.1069 [0.0547; 0.1983] | Random | 3 | 0 | 253 | 0.0106 [0.0021; 0.0509] | Fixed | |||
Overall | 6 | 36 | 387 | 0.1016 [0.0741; 0.1380] | Fixed | 5 | 0 | 356 | 0.0109 [0.0031; 0.0369] | Fixed | |||
Vomiting | Nivolumab | 1 | 6 | 80 | 0.0750 | 1 | 0 | 80 | 0 | ||||
Pembrolizumab | 3 | 13 | 266 | 0.0533 [0.0311; 0.0899] | Fixed | 2 | 0 | 235 | 0.0067 [0.0009; 0.0463] | Fixed | |||
Overall | 4 | 19 | 346 | 0.0594 [0.0381; 0.0913] | Fixed | 3 | 0 | 315 | 0.0065 [0.0013; 0.0318] | Fixed | |||
Constipation | Nivolumab | 2 | 7 | 97 | 0.0746 [0.0359; 0.1484] | Fixed | 0.134 | 2 | 0 | 97 | 0.0130 [0.0018; 0.0871] | Fixed | |
Pembrolizumab | 2 | 8 | 241 | 0.0349 [0.0175; 0.0683] | Fixed | 1 | 0 | 210 | 0 | ||||
Overall | 4 | 15 | 338 | 0.0495 [0.0300; 0.0807] | Fixed | 3 | 0 | 307 | 0.0074 [0.0015; 0.0358] | Fixed | |||
Stomatitis | Nivolumab | 2 | 4 | 105 | 0.0456 [0.0171; 0.1157] | Fixed | 2 | 2 | 105 | 0.0229 [0.0057; 0.0873] | Fixed | ||
HEPATIC | |||||||||||||
Lipase increased | Nivolumab | 2 | 5 | 105 | 0.0514 [0.0215; 0.1179] | Fixed | 4 | 18 | 428 | 0.0454 [0.0288; 0.0710] | Fixed | ||
AST increased | Nivolumab | 1 | 4 | 80 | 0.0500 | 1 | 2 | 80 | 0.0250 | ||||
Pembrolizumab | 1 | 2 | 31 | 0.0645 | 1 | 1 | 31 | 0.0323 | |||||
Overall | 2 | 6 | 111 | 0.0544 [0.0246; 0.1159] | Fixed | 2 | 3 | 111 | 0.0272 [0.0088; 0.0810] | Fixed | |||
ALT increased | Nivolumab | 1 | 3 | 80 | 0.0375 | 2 | 9 | 323 | 0.0279 [0.0146; 0.0528] | Fixed | |||
Pembrolizumab | 1 | 2 | 31 | 0.0645 | 1 | 1 | 31 | 0.0323 | |||||
Overall | 2 | 5 | 111 | 0.0465 [0.0195; 0.1070] | Fixed | 3 | 10 | 354 | 0.0283 [0.0153; 0.0518] | Fixed | |||
ENDOCRINE | |||||||||||||
Hypothyroidism | Nivolumab | 2 | 7 | 40 | 0.1789 [0.0493; 0.4780] | Random | 0.251 | 2 | 0 | 40 | 0.0241 [0.0034; 0.1520] | Fixed | 0.463 |
Pembrolizumab | 3 | 33 | 259 | 0.1279 [0.0924; 0.1745] | Fixed | 2 | 1 | 228 | 0.0098 [0.0025; 0.0385] | Fixed | |||
Overall | 5 | 40 | 299 | 0.1377 [0.1025; 0.1826] | Fixed | 4 | 1 | 268 | 0.0132 [0.0043; 0.0403] | Fixed | |||
NEURAL | |||||||||||||
Headache | Nivolumab | 2 | 6 | 97 | 0.0844 [0.0080; 0.5126] | Random | 2 | 0 | 97 | 0.0130 [0.0018; 0.0871] | Fixed | ||
Pembrolizumab | 1 | 13 | 210 | 0.0619 | 1 | 0 | 210 | 0 | |||||
Overall | 3 | 19 | 307 | 0.0768 [0.0246; 0.2155] | Random | 3 | 0 | 307 | 0.0074 [0.0015; 0.0358] | Fixed | |||
Back pain | Nivolumab | 2 | 4 | 97 | 0.0544 [0.0113; 0.2244] | Random | 2 | 0 | 97 | 0.0130 [0.0018; 0.0871] | Fixed | 0.669 | |
Pembrolizumab | 1 | 4 | 210 | 0.0190 | 2 | 1 | 241 | 0.0132 [0.0007; 0.2022] | Random | ||||
Overall | 3 | 8 | 307 | 0.0358 [0.0119; 0.1026] | Random | 4 | 1 | 338 | 0.0184 [0.0059; 0.0559] | Fixed | |||
Myalgia | Nivolumab | 2 | 8 | 97 | 0.0838 [0.0424; 0.1587] | Fixed | 2 | 0 | 97 | 0.0130 [0.0018; 0.0871] | Fixed | ||
Pembrolizumab | 1 | 5 | 210 | 0.0238 | 1 | 0 | 210 | 0 | |||||
Overall | 3 | 13 | 307 | 0.0552 [0.0216; 0.1343] | Random | 3 | 0 | 307 | 0.0074 [0.0015; 0.0358] | Fixed | |||
Arthralgia | Nivolumab | 1 | 11 | 80 | 0.1375 | 1 | 0 | 80 | 0.0062 | ||||
Pembrolizumab | 1 | 8 | 210 | 0.0381 | 1 | 1 | 210 | 0.0048 | |||||
Overall | 2 | 19 | 290 | 0.0742 [0.0201; 0.2388] | Random | 2 | 1 | 290 | 0.0069 [0.0017; 0.0270] | Fixed | |||
HEMATOLOGIC | |||||||||||||
Anemia | Nivolumab | 2 | 8 | 162 | 0.0507 [0.0256; 0.0982] | Fixed | 0.955 | 2 | 3 | 162 | 0.0331 [0.0124; 0.0850] | Fixed | 0.945 |
Pembrolizumab | 2 | 11 | 235 | 0.0579 [0.0005; 0.8856] | Random | 2 | 5 | 235 | 0.0296 [0.0003; 0.7551] | Random | |||
Overall | 3 | 16 | 317 | 0.0576 [0.0098; 0.2741] | Random | 3 | 8 | 317 | 0.0292 [0.0046; 0.1631] | Random | |||
Neutropenia | Nivolumab | 2 | 10 | 162 | 0.0670 [0.0364; 0.1203] | Fixed | 0.649 | 3 | 12 | 405 | 0.0322 [0.0183; 0.0558] | Fixed | 0.243 |
Pembrolizumab | 3 | 14 | 253 | 0.0558 [0.0333; 0.0921] | Fixed | 4 | 14 | 286 | 0.0685 [0.0216; 0.1969] | Random | |||
Overall | 5 | 24 | 415 | 0.0602 [0.0407; 0.0883] | Fixed | 7 | 26 | 691 | 0.0479 [0.0234; 0.0953] | Random | |||
Lymphopenia | Nivolumab | 3 | 8 | 185 | 0.0474 [0.0239; 0.0921] | Fixed | 3 | 5 | 185 | 0.0276 [0.0115; 0.0647] | Fixed | ||
Platelet count decreased | Nivolumab | 2 | 5 | 103 | 0.0553 [0.0038; 0.4766] | Random | 2 | 0 | 103 | 0.0113 [0.0016; 0.0761] | Fixed | ||
Pembrolizumab | 1 | 11 | 25 | 0.4400 | 1 | 5 | 25 | 0.2000 | |||||
Overall | 3 | 16 | 128 | 0.1354 [0.0225; 0.5159] | Random | 3 | 5 | 128 | 0.0414 [0.0034; 0.3530] | Random | |||
Leukopenia | Nivolumab | 2 | 6 | 162 | 0.0390 [0.0176; 0.0841] | Fixed | 2 | 3 | 162 | 0.0331 [0.0124; 0.0850] | Fixed |
Bold values indicates the classification of the adverse events.