Table 6.
Common adverse events (AEs) associated with everolimus in previous studies
| Study (year) | n | Regimen | AEs, all grade (grade 3/4), % |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Stomatitis | Rash | Diarrhea | Fatigue | Infection | Pneumonitis | Hyperglycemia | Plt decrease | Anemia | ||||
| Eve monotherapy | ||||||||||||
| Yao et al (2011)[22] | 207 | Eve | 64(7)* | 49(<1) * | 34(3)* | 31(2)* | 23(2)* | 17(2)* | 13(5) | 13(4)* | 17(6) * | |
| Yao et al (2016)[65] | 225 | Eve | 60(4) | 37(1) | 26(2) | 20(3) | 28(5) | 10(<1) | - | 10(4) | 14(0) | |
| Yao et al (2016)[23] | 205 | Eve | 63(9) * | 27(1) * | 31(7) * | 31(3) | 29(7) * | 16(1) * | 10(3) | -(<1) | 16(4) * | |
| Panzuto et al [91] | 169 | Eve | 22(2) | - | - | - | - | 19(8) | 17(1) | 22(8) | 20(5) | |
| Pavel et al (2016) [166] | 123 | Eve (panNET) | 19(3) | 7(2) | 32(9) | 15(8) | 39(19) | 5(2) | 5(3) | 5(2) | 11(3) | |
| 117 | Eve (non panNET) | 19(3) | 7(2) | 32(9) | 15(8) | 39(19) | 5(2) | 5(3) | 5(2) | 11(3) | ||
| Berardi et al (2017)[92] | 116 | Eve | -(4) | -(1) | -(3) | -(2) | - | -(2) | -(3) a | -(4) | -(1) | |
| Liu et al (2016) [93] | 53 | Eve | 36(2) | 19(0) | - | 15(2) | - | 9(2) | 23(9) | 9(0) | 13(8) | |
| Lee et al (2017) [94] | 47 | Eve | 85(0) | 57(0) | 21(6) | - | 53(21) | 15(4) | 34(4) | 28(9) | 34(6) | |
| Lee et al (2017) [95] | 40 | Eve | 48(5) | 33(3) | 10(3) | - | - | 3(0) | - | 8(0) | 13(3) | |
| Oh et al (2012)[87] | 32 | Eve | 18(6) | 29(0) | 27(3) | - | - | - | 12(6) | 15(15) | 12(6) | |
| Salazar et al (2017)[86] | 31 | Eve | 65(6) | 42(0) | 55(3) | 32(36) | - | 16(3) | 35(6) | 23(0) | 35(10) | |
| Angelousi et al
(2017)[98] |
20 11 |
Eve (1st line) Eve (2nd line) |
10(0) 9(0) |
25(0) 18(0) |
15(0) b 45(9) b |
10(0) 18(0) |
- - |
25(5) 18(9) |
25(5) 18(0) |
25(5)c 27(5)c |
25(5)c 27(5)c |
|
| Kamp et al (2013) [97] | 24 | Eve | 42(4) | 25(4) | 4(4) | 33(8) | 8(0) | 38(0) | 25(13) | 17(8) | 21(0) | |
| Yoo et al (2017) [99] | 17 | Eve | 59(6) | 41(0) | 29(0) | 29(0) | - | 18(12) | - | 12(6) | 29(0) | |
| Eve-combined therapy | ||||||||||||
| Pavel et al (2011)[21] | 216 | Eve + Oct | 62(7) * | 37(1) * | 27(6) * | 31(7) | 20(5) * | 12(2) * | 12(5) * | 14(5) * | 15(1) * | |
| Yao et al (2010)[72] | 115 45 |
Eve Eve + Oct |
45(4) 49(2) |
40(1) 44(0) |
39(4) 31(0) |
31(4) 36(2) |
- - |
6(0) 13(0) |
13(4) 13(4) |
8(3) 13(9) |
13(4) 16(4) |
|
| Yao et al (2008)[20] | 60 | Eve + Oct | 69(8) | 64(5) | - | -(11) | - | 7(2) | 70(9) | 35(5) | -(3) | |
| Bajetta et al (2014)[73] | 50 | Eve + Oct | 62(10) | 48(2) | 60(22) | - | - | 6(0) | 18(0) | 12(0) | 8(2) | |
| Dasari et al (2015)[78] | 19 | Eve + Oct + cixutumumab |
63(11) | 42(0) | 58(0) | 74(21) | 16(5) | - | 63(11) | 53(0) | 11(5) | |
| Kulke et al (2017)[75] | 79 81 |
Eve + Pas Eve |
59(9) 63(9) |
24(0) 30(0) |
63(5) 53(4) |
27(4) 35(4) |
15(0) 14(0 |
8(1) 12(1) |
76(37) 27(11) |
- - |
27(5) 26(5 |
|
| Dasari et al (2015)[76] | 42 41 |
Eve Eve + Pas |
72(10) 37(5) |
33(7) 12(0) |
50(7) 76(20) |
19(2) 34(10) |
9(2) 12(0) |
5(5) 15(5) |
46(17) 83(24) |
23(2) 17(0) |
31(2) 25(5) |
|
| Chan et al (2012)[77] | 22 | Eve + Pas | 48(5) | 48(5) | 62(5) | 76(0) | - | - | 90(38) | 76(14) | 76(0) | |
| Chan et al (2013)[83] | 43 | Eve + temozolomide |
63(2) | 53(5) | 51(2) | 77(2) | - | 7(0) | 72(19) | 67(16) | 65(0) | |
| Yao et al (2015)[96] | 39 | BV or Eve → Bv + Eve |
61(2) | 15(2) | 49(15) | 61(7) | 56(7) | - | 44(10) | 20(5) | 32(5) | |
| Chan et al (2013)[84] | 21 | Eve + sorafenib | 38(0) | 81(14) | 67(14) | 76(0) | 10(0) | 5(5) | 76(10) | 86(14) | 86(0) | |
Bv, bevacizumab; Eve, everolimus; Plt, platelet; panNET, pancreatic NET; Oct, octreotide; Pas, pasireotide.
*
Frequencies of all grade AEs more than 10% higher than control arm.
a
Reported as metabolic toxicities.
b
Reported as gastrointestinal intolerance.
c
Reported as haematologic toxicities.