Table 5.
Comparison of individual AEs of any grade for dabrafenib plus trametinib versus vemurafenib plus cobimetinib
| Incidence, number (%) | ITC results | |||||||
|---|---|---|---|---|---|---|---|---|
| COMBI-v | coBRIM | |||||||
| AE type | D + T (n = 350) | V (n = 349) | V (n = 246) | V + C (n = 247) | RR | LCI | UCI | p value |
| Abdominal pain | 39(11.1) | 32(9.2) | 19(7.7) | 25(10.1) | 0.93 | 0.45 | 1.91 | 0.8378 |
| Alopecia | 23(6.6) | 136(39) | 73(29.7) | 37(15.0) | 0.33 | 0.19 | 0.58 | 0.0001 |
| Anemia | 26(7.4) | 21(6.0) | 20(8.1) | 32(13.0) | 0.77 | 0.36 | 1.67 | 0.5147 |
| Arthralgia | 93(26.6) | 182(52.2) | 99(40.2) | 89(36.0) | 0.57 | 0.42 | 0.77 | 0.0003 |
| Asthenia | 61(17.4) | 58(16.6) | 40(16.3) | 43(17.4) | 0.98 | 0.59 | 1.63 | 0.9368 |
| Blurred vision | 17(4.9) | 18(5.2) | 6(2.4) | 25(10.1) | 0.23 | 0.08 | 0.67 | 0.0075 |
| Increased blood creatinine | 15(4.3) | 37(10.6) | 20(8.1) | 34(13.8) | 0.24 | 0.11 | 0.52 | 0.0003 |
| Chills | 116(33.1) | 28(8.0) | 12(5.0)a | 20(7.9)# | 2.63 | 1.19 | 5.82 | 0.0167 |
| Chorioretinopathy | 2(<1) | 1(<1) | 1(<1) | 31(12.6) | 0.06 | 0.00 | 1.45 | 0.0843 |
| Constipation | 54(15.4) | 25(7.2) | 26(10.6) | 24(9.7) | 2.34 | 1.17 | 4.68 | 0.0160 |
| Cough | 77(22.0) | 40(11.5) | 30(12.2) | 19(7.7) | 3.04 | 1.59 | 5.83 | 0.0008 |
| Cutaneous squamous cell carcinoma | 5(1.4) | 63(18.1) | 27(11.3)a | 7(2.8)# | 0.32 | 0.10 | 1.09 | 0.0685 |
| Decreased appetite | 44(12.6) | 70(20.1) | 50(20.3) | 46(18.6) | 0.68 | 0.42 | 1.13 | 0.1361 |
| Dermatitis acneiform | 23(6.6) | 20(5.7) | 22(8.9) | 34(13.8) | 0.75 | 0.34 | 1.61 | 0.4539 |
| Diarrhea | 120(34.3) | 136(39.0) | 82(33.3) | 150(60.7) | 0.48 | 0.36 | 0.64 | <0.0001 |
| Dry skin | 33(9.4) | 67(19.2) | 39(15.9) | 35(14.2) | 0.55 | 0.31 | 0.97 | 0.0407 |
| Dysgeusia | 23(6.6) | 47(13.5) | 26(10.6) | 37(15.0) | 0.34 | 0.18 | 0.67 | 0.0018 |
| Edema peripheral | 48(13.7) | 42(12.0) | 28(11.4) | 31(12.6) | 1.03 | 0.56 | 1.91 | 0.9165 |
| Erythema | 35(10.0) | 42(12.0) | 33(13.4) | 24(9.7) | 1.15 | 0.60 | 2.20 | 0.6795 |
| Fatigue | 110(31.4) | 117(33.5) | 80(32.5) | 85(34.4) | 0.89 | 0.64 | 1.23 | 0.4697 |
| Headache | 112(32.0) | 84(24.1) | 39(15.9) | 41(16.6) | 1.27 | 0.80 | 2.03 | 0.3172 |
| Hyperkeratosis | 18(5.1) | 89(25.5) | 75(30.5) | 27(10.9) | 0.56 | 0.30 | 1.06 | 0.0734 |
| Hypertension | 103(29.4) | 82(23.5) | 19(7.7) | 37(15.0) | 0.65 | 0.36 | 1.15 | 0.1399 |
| Increased ALT | 49(14.0) | 61(17.5) | 44(17.9) | 65(26.3) | 0.54 | 0.34 | 0.88 | 0.013 |
| Increased AST | 42(12.0) | 46(13.2) | 31(12.6) | 60(24.3) | 0.47 | 0.27 | 0.82 | 0.008 |
| Increased blood ALP | 26(7.4) | 30(8.6) | 22(8.9) | 36(14.6) | 0.53 | 0.26 | 1.08 | 0.0799 |
| Increased blood CPK | 10(2.9) | 2(<1) | 7(2.9) | 80(32.4) | 0.44 | 0.08 | 2.37 | 0.3378 |
| Increased GGT | 38(10.9) | 33(9.5) | 44(17.9) | 54(21.9) | 0.94 | 0.53 | 1.66 | 0.8292 |
| Keratocanthoma | 2(<1) | 35(10.0) | 20(8.4)a | 2(<1)# | 0.61 | 0.08 | 4.58 | 0.6269 |
| Keratosis pilaris | 4(1.1) | 48(13.8) | 26(10.6) | 8(3.2) | 0.27 | 0.08 | 0.97 | 0.0442 |
| Myalgia | 66(18.8) | 56(16.1) | 30(12.2) | 28(11.3) | 1.26 | 0.71 | 2.26 | 0.4298 |
| Nausea | 126(36.0) | 130(37.3) | 62(25.2) | 102(41.3) | 0.59 | 0.43 | 0.82 | 0.0015 |
| Pain in extremity | 45(12.9) | 44(12.6) | 35(14.2) | 24(9.7) | 1.49 | 0.80 | 2.79 | 0.2079 |
| Photosensitivity reaction | 15(4.3) | 81(23.2) | 93(37.8) | 118(47.8) | 0.15 | 0.08 | 0.26 | <0.0001 |
| Pruritus | 36(10.3) | 78(22.4) | 46(18.7) | 48(19.4) | 0.44 | 0.26 | 0.74 | 0.0020 |
| Pyrexia | 193(55.1) | 74(21.2) | 56(22.8) | 69(27.9) | 2.12 | 1.45 | 3.09 | 0.0001 |
| Rash | 84(24.0) | 150(43.0) | 94(38.2) | 98(39.7) | 0.54 | 0.39 | 0.74 | 0.0001 |
| Rash maculopapular | 13(3.7) | 28(8.0) | 38(15.5) | 38(15.4) | 0.46 | 0.22 | 1.00 | 0.0490 |
| SCC of skin | 2(<1) | 21(6.0) | 31(12.6) | 8(3.2) | 0.37 | 0.07 | 1.88 | 0.2310 |
| Skin papilloma | 8(2.3) | 82(23.5) | 29(11.8) | 12(4.9) | 0.24 | 0.09 | 0.62 | 0.0033 |
| Sun burn | 3(<1) | 51(14.6) | 43(17.5) | 34(13.8) | 0.07 | 0.02 | 0.25 | <0.0001 |
| Vomiting | 107(30.6) | 55(15.8) | 31(12.6) | 60(24.3) | 1.01 | 0.62 | 1.64 | 0.9798 |
a N = 239; # N = 254
AE adverse event, ALP alkaline phosphatase, ALT alanine aminotransferase, AST aspartate aminotransferase, CI confidence interval, CPK creatine phosphokinase, GGT gamma-glutamyltransferase, LCI lower 95% CI, RR risk ratio, SCC squamous cell carcinoma, UCI upper 95% CI