TABLE 3.
Overview of hepatotoxicity in PKIs (combination) therapy. Total number of PKIs combination therapy N = 8.
| PKI | Incidence of AST elevations (%) | Incidence of ALT elevations (%) | Latency to onset of hepatotoxicity (weeks) | Time to recovery (weeks) | Cases of hepatitis or hepatic failure? | Fatal cases due to hepatotoxicity | ||
|---|---|---|---|---|---|---|---|---|
| All grades | Grade 3–4 | All grades | Grade 3–4 | |||||
| Abemaciclib + endocrine therapy | 14.2 | 4.2 | 15.1 | 6.1 | 8.5 | 2.0 | Yes a | Yes a |
| Alpelisib + fulvestrant | 10.9 a | 2.8 a | 44.0 | 4.2 b | – | – | – | – |
| Cobimetinib + vemurafenib | 71.0 | 7.0 | 67.0 | 11.0 | – | – | – | – |
| Lenvatinib (Kisplyx®) + everolimus | 4.8 | – | 9.7 | – | 12.1 | – | Yes | Yes |
| Nintedanib + docetaxel | 31.3 a | – | 38.8 a | – | 2.0 a | 2.0 a | Yes a | Yes |
| Palbociclib + letrozole or fulvestrant | 55.5 | 3.9 b | 46.1 | 2.5 | – | – | Yes a | Yes a |
| Ribociclib + endocrine therapy | – | 6.7 | – | 9.7 | 12.1 | 3.1 | Yes a | Yes a |
| Tucatinib + trastuzumab and capecitabine | – | 5.0 | – | 6.0 | 5.2 | 3.0 | – | – |
Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase.
a
Not sufficient data in SmPC, data extracted from EPAR.
b
Only grade 3 no grade 4.