<p>Complete Response to the Sequential Treatment with Regorafenib Followed by PD-1 Inhibitor in a Sorafenib-Refractory Hepatocellular Carcinoma Patient</p>

Abstract

Most patients diagnosed with hepatocellular carcinoma (HCC) have advanced diseases, and many are not eligible for curative therapies. There is growing evidence suggesting that the combination treatment of PD-1/PD-L1 inhibitors and tyrosine kinase inhibitors (TKIs) is becoming a prospective trend for advanced HCC. For those HCC patients with sorafenib resistance, the efficacy of regorafenib combined with PD-1/PD-L1 inhibitors remains unclear. Herein, we represent a case of HCC with lung metastasis in the setting of Hepatitis B virus (HBV)-induced liver cirrhosis responding dramatically to the sequential treatment with regorafenib followed by PD-1 inhibitor after initial liver resection. A 51-yearold man diagnosed with alpha fetoprotein (AFP)-negative HCC underwent liver resection in September 2015 and was found to have solitary liver recurrence and multiple lung metastases in March 2017. He received microwave coagulation therapy (MCT) and trans-arterial chemoembolization (TACE) for liver tumor and treatment was started with sorafenib 400 mg twice daily for controlling lung metastases. In December 2018, an abdominal computerized tomography (CT) scan showed two new lesions in the liver. In March 2019, disease progression of lung metastases was measured and he received 160 mg regorafenib once daily. After a short period of partial response, in December 2019, due to the progression of the disease, he started treatment with regorafenib 160 mg in combination with sintilimab (PD-1 inhibitor) (200 mg, 3 weeks as a cycle). Surprisingly, after five cycles of sintilimab injection, he showed complete response in target lesions. There was no clinical evidence of disease progression, and the side-effects were mild. The current overall survival (OS) is 58 months. Data from this clinical case report suggest that sequential treatment with regorafenib followed by PD-1 inhibitor is a promising therapeutic option for sorafenib-refractory cases of HCCs.

Optimal timing of combining sorafenib with trans-arterial chemoembolization in patients with hepatocellular carcinoma: A meta-analysis

“…Nevertheless, there is more evidence to suggest that combination therapy with PD-1/PD-L1 inhibitors and tyrosine kinase inhibitors (TKIs) is becoming a future trend in advanced HCC [34] . We think that combination loco-regional therapy with systemic therapy in unresectable HCC patients will more mature and become standardized in the next 5 years, and we believe that more studies will be conducted in the future to compare the safety and efficacy of loco-regional therapy combined with immunosuppressive agents versus sorafenib in order to maximize the clinical benefit .…”

Long-term survival of a patient with microsatellite-stable refractory colorectal cancer with regorafenib and PD-1 inhibitor sintilimab: a case report and review of literature

“…Also, Zhang et al showed that the sequential treatment with regorafenib followed by sintilimab in a Sorafenib-Refractory hepatocellular carcinoma patient achieved a CR in their case report [ 22 ]. The significant highlight of the present case study is that it demonstrates that the combination of regorafenib plus sintilimab administered in an MSS stable CRC patient refractory to previous lines of treatment achieved CR and stable disease culminating antitumor activity.…”

Response of Scalp and Skull Metastasis to Anti-PD-1 Antibody Combined with Regorafenib Treatment in a Sorafenib-Resistant Hepatocellular Carcinoma Patient and a Literature Review

“…Previously, we reported an advanced HCC case with liver recurrence and lung metastasis 18 months after radical resection, which was completely relieved after treatment with sorafenib followed by regorafenib plus sintilimab. 21 Based on our experience of using TKIs and ICIs, we describe a special case with skull and lung metastasis, and portal vein invasion, classified as IIIb in CNLC system and stage C in BCLC system, which was successfully managed by systemic therapy, with a review of the related literature. These findings will hopefully contribute to the therapeutic options available for treatment of advanced HCC, particularly for skull metastasis.…”