Table 4

Grade 3 and grade 4 toxicities of CDK4/6 inhibitors

Reference Therapy Neutropenia (%) Febrile neutropenia (%) Leucopenia (%) Anaemia (%) Thromboctytopenia (%) Fatigue (%) Other (%) Discontinuation (%)
Slamon et al 13 Letrozole + palbociclib vs letrozole17(grade 4) (≈ 2 DLT)0Common--Common-8 (dose interruption)
Clark et al 14 Palbociclib + paclitaxel594 (DLT)----Grade 3 AST/ALT(DLT)67 (dose interruption)
DeMichele et al 49 Palbociclib513515220Lymphopenia 303
Finn et al 16 36 Letrozole + palbociclib
Letrozole
51
1
0
0
19
0
6
1
2
0
4
1
-13
2
Finn et al 17 Letrozole + palbociclib
Letrozole
All grades
79.5; grade 3: 56.1
All grades
6.3
37.4
27.5
Nausea 35.1
26.1
9.7
5.9
Turner et al 59, Cristofanilli et al 18 Palbociclib + fulvestrant
Placebo + fulvestrant ± goserelin
65.
1
1
1
28
2
3
2
2
0
2
1
-4
2
Tolaney et al 23 Abemaciclib +
(A) letrozole (B) anastrozole (C) tamoxifen (D) exemestane
(E) exemestane + everolimus (F) exemestane + trastuzumab
1714Diarrhoea 31
Nausea 6
Vomiting 3
Abdominal pain 3
Patnaik et al 22 Abemaciclib*
Abemaciclib + fulvestrant
11
31
232
8
Diarrhoea 5
Nausea 3
Vomiting 2
Diarrhoea 8
Dickler et al 24 AbemaciclibCommon (number NR)Common AE: diarrhoea, nausea, decreased appetite, abdominal pain number NR)6.8%
Juric et al 25 26 A1: ribociclib + letrozole.
A2: alpelisib + letrozole
A3: ribociclib + letrozole + BYL
43 (A1)
22 (A3)
2 (A1)--11 (A3)Lymphopenia 4 (A1) Hyperglycaemia, 17 (A3)
Nausea, 6 (A3)
NR (A1)
22(A3)
Bardia et al 27 Ribociclib + everolimus + exemestane
Ribociclib + exemestane
45.78.65.76 DLT: 1 febrile neutropenia, 2 ALT elevations,
2 thrombocytopenia,
1 mucositis
2.9
  • *Toxicity reported for 132 patients (47 with breast cancer).

  • AE, adverse event; ALT, alanine transaminase; AST, aspartate transaminase; DLT, dose limiting toxicity; NR, not reported.