Abstract 999P
Background
Cabozantinib (CABO) has been approved by the European Medicine Agency (EMA) as a second or third-line therapy for hepatocellular carcinoma (HCC) previously treated with sorafenib. CABO is also being tested in combination with immune checkpoint inhibitors in the frontline setting. Real-life clinical data of CABO for HCC are lacking, as its approval by most national drugs agencies is still pending. In Italy, the manufacturing company can currently provide CABO for HCC patients with no therapeutic alternatives, after an individual request by physicians, in the legal context of named patient use.
Methods
We evaluated clinical data and outcome of HCC patients who received CABO in the mentioned context in different Italian centres.
Results
Fifty-two patients from 7 centres received CABO according to EMA recommendations (median follow-up: 7.1 months). All patients had preserved liver function (Child-Pugh A), mostly advanced HCC (80.8%) and in a third-line setting (88.0%). Rates of PS>0, macrovascular invasion, extrahepatic spread, and alfa-fetoprotein>400 ng/ml were 42.3%, 34.6%, 75.0%, and 38.5%, respectively. Median OS was 12.9 months (95% CI 8.7-17.1). Median PFS was 5.1 months (95% CI 2.7-7.5). Disease control rate was 59.2%. Most common treatment-related adverse events (AEs) were: fatigue (75.0%), diarrhoea (59.6%), anorexia (44.2%), HFSR (42.3%), weight loss (28.8%), hypertension (26.9%), abdominal pain (23.1%), dysphonia (17.3%), ALT increase (17.3%), hypothyroidism (13.5%), nausea (13.5%), mucositis (13.5%), thrombocytopenia (11.5%). Most common treatment-related Grade 3-4 AEs were: fatigue (9.6%), HFSR (7.7%), hypertension (5.8%), ALT increase (5.8%). No treatment-related deaths were observed. Serious AEs included: liver failure (n=1), pulmonary embolism (n=1), cerebral haemorrhage (n=1). Most patients (78.8%) required temporary drug interruptions. Permanent dose reduction from 60 mg to 40 or 20 mg/day was needed in 46.2% and 17.3% of patients, respectively. Rate of permanent discontinuation for intolerance was 17.3%.
Conclusions
In a real-life scenario (mostly in a third-line setting) CABO maintained efficacy data comparable with those reported in its registrative trial. Also, the safety profile was acceptable with no new signals.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
F. Tovoli: Advisory/Consultancy: Bayer AG.F. Trevisani: Advisory/Consultancy: Bayer AG; Advisory/Consultancy: Sirtex; Advisory/Consultancy: Alfasigma; Advisory/Consultancy: BMS. G. Brandi: Advisory/Consultancy: Eli Lilly. F. Piscaglia: Advisory/Consultancy: Alkermes; Advisory/Consultancy: Astrazeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer AG; Speaker Bureau/Expert testimony: Bracco; Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Speaker Bureau/Expert testimony: Ipsen; Speaker Bureau/Expert testimony: LaForce; Advisory/Consultancy: Roche; Speaker Bureau/Expert testimony: Tiziana Life Sciences. All other authors have declared no conflicts of interest.