O-7 LIVER TOXICITY OF TYROSINE KINASE INHIBITORS: A DESCRIPTIVE ANALYSIS FROM SLATINDILI NETWORK

Introduction and Objectives

Tyrosine kinases (TKs) are a family of proteins with a critical role in controlling cancer phenotypes, and many TK inhibitors (TKI) as anti-cancer agents are available. Mandatory black box warning has been issued for some TKI since 2012, and DILI is the most frequent adverse event quoted. This study aimed to describe the most crucial aspects of DILI linked to TKI in the SLATINDILI registry.

Materials and Methods

We revised data concerning liver injury related to any TKI in the SLATINIDLI registry and consigned epidemiological information, latency, implied drug, biochemical, severity, and evolution.

Results

From thirteen cases identified, imatinib and pazopanib represented four and three cases each. The mean age was 58 years, and eleven were female. Median latency was 64 days, with median ALT and ALP at the onset of 452 U/L (range 233-941) and 199 U/L (range 85-1621), respectively; a hepatocellular pattern was seen in ten cases. Autoimmune/Allergic features were present in seven patients. Resolution of liver injury occurred on an average of 183 days. No death was consigned. Liver function tests (LFTs) worsened during an initial period (>7 days) after drug withdrawal in six patients (cases 1,2,3,5,9 and 12), and two of them were treated with corticoids. Table 1 resumes data.

Conclusions

Hepatocellular acute liver injury with/without jaundice is the most common presentation of DILI linked to TKI. Clinicians should be aware that LFTs may worsen after drug withdrawal and monitor these patients before making a treatment decision.

Age /Sex

Table

	Age /Sex	TKI /Likelihood Score*	Indication	Latency (days)	Pattern	TB onset/peak	ALT U/L onset/peak	Resolution (days)
r1*	61/F	IMATINIB/B	Leukemia	92	HC	1/11	791/880	510
2*	73/F	IMATINIB/B	Renal cancer	124	HC	1.85/3.19	941/988	138
3*	58/M	MASITINIB/-	ALS	14	HC	0.4/0.4	351/436	230
4	50/F	BOSUTINIB/D	Leukemia	43	HC	0.3/0.3	233/233	169
5*	28/F	IMATINIB/B	Leukemia	176	HC	3.6/24	658/658	217
6	68/M	PAZOPANIB/C	Renal cancer	64	M	3.7/3.7	775/445	-
7	75/F	PAZOPANIB/C	Renal cancer	44	M	11/11	508/508	203
8	75/F	PAZOPANIB/C	Renal cancer	-	HC	3.8/3.8	403/403	204
9*	40/F	LENVATINIB/D	HCC	42	HC	2.5/12.6	750/750	120
10	65/F	IMATINIB/B	Breast cancer	150	HC	0.89/0.89	452/452	62
11	70/F	BOSUTINIB/D	Leukemia	112	-	0.3/0.3	341/341	83
12*	49/F	PALBOCICLIB/	Breast cancer	28	HC	0.37/0.96	281/1796	76
13	41/F	CABOZANTINIB/E	Renal cancer	84	HC	0.34/0.34	247/247	-

*Likelihood of association with DILI, based upon the known potential of the drug to cause such injury. HCC hepatocellular carcinoma; ALS amyotrophic lateral sclerosis; HC hepatocellular pattern; M mixed pattern; M male; F: female.