Safety and Efficacy of Low-Dose Regorafenib Combined with Nivolumab in Patients with Advanced HCC in Progression Beyond Two or More Lines of Tyrosine Kinase Inhibitors: Case Reportsand Short Review of the Literature
DOI:
https://doi.org/10.47363/JDCRS/2024(5)146Keywords:
Hepatocellular Carcinoma, Checkpoint Inhibitor, Tyrosine Kinase Inhibitor, Nivolumab, RegorafenibAbstract
Background and Aims: A few clinical studies have suggested that low doses of anti-angiogenic molecules might enhance the therapeutic effects of anti-PD1 in HCC and may improve their tolerance. Here, we present case reports of patients treated with low-dose regorafenib combined with nivolumab after the failure of at least two lines of oral chemotherapy.
Design: We report 12 observations of patients with advanced HCC in progression after at least two lines of tyrosine kinase inhibitor (TKI) therapy who received regorafenib (starting with 80 mg/day) combined with nivolumab (3 mg/kg/14 days/IV) until progression or unacceptable toxicity.The safety based on NCI-CTCAE 4 and the clinical efficacy (progression free survival, overall response rate, disease control rate, time to treatment response and median duration of response) were retropectively assessed.
Results: Median age was 68 years (IQR [64; 71.5]), and 75% had BCLC-C. The median follow-up was 18.8 months (IQR [11.5; 23.4]) and the median duration of treatment was 10 months (IQR [3.8 ;17]). Because of the frequent early adverse events associated with regorafenib, this treatment remained at an initial dose of 80 mg/day in all patients. Of note, most grade III adverse events (AEs) occurred later after a median duration of combined treatment of 10.5 months (IQR ), were also mainly due to regorafenib, but allowed the pursuit of nivolumab alone [5,11,5]. The therapeutic combination led to a partial response in three patients (30 %) and a stable disease in two patients (20 %), corresponding to a disease control rate of 50% at 12 months in the 10 patients who were trated more than 2 months. The median TTR was 2 months (IQR) [1-9]. The median duration of disease control and response was 22 (IQR [21;
24] ) and 24 months (IQR), respectively [23-25].
Conclusion: Combination of low-dose regorafenib and nivolumab might be associated with an interesting disease control rate and manageable safety profile in patients with progressive advanced HCC beyond the second-line treatment with tyrosine kinase inhibitors.
