Regorafenib Versus Nivolumab After Sorafenib Failure: Real‐World Data in Patients With Hepatocellular Carcinoma

Choi, Won‐Mook; Choi, Jonggi; Lee, Danbi; Shim, Ju Hyun; Lim, Young Suk; Lee, Han Chu; Chung, Young‐Hwa; Lee, Young-Sang; Park, Sook Ryun; Ryu, Min‐Hee; Ryoo, Baek‐Yeol; Lee, So Jung; Kim, Kang Mo

doi:10.1002/hep4.1523

Cited by 34 publications

(40 citation statements)

References 38 publications

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“…analyses [18]. Consequently, these real-world clinical experiences indicated that using nivolumab might produce consistent OS compared to using regorafenib for patients after sorafenib failure.…”

Section: Discussionmentioning

confidence: 98%

Nivolumab vesus Regorafenib in patients with hepatocellular carcinoma after Sorafenib failure

Kuo

Yen

Chen

et al. 2021

Preprint

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Nivolumab and regorafenib are approved second-line therapies for patients with hepatocellular carcinoma (HCC) after sorafenib failure. This study compared the effectiveness of nivolumab and regorafenib following sorafenib. We retrospectively enrolled HCC patients who had undergone nivolumab or regorafenib after sorafenib failure. Treatment response, treatment related adverse events (TRAE) and clinical outcomes of study patients were recorded and analyzed. A total of 90 patients (Male/Female: 67/23, mean age: 63 year) were enrolled, including 32 patients in the Nivolumab group and 58 patients in the Regorafenib group. The Nivolumab group had better objective response rates (16% vs 6.4%) and disease control rates (44% vs 31.9%) than the Regorafenib group, but there was no statistical difference. The comparison of time to progression (3.0 months vs 2.6 months, p=0.786) and overall survival (OS) (14 months vs 11 months, p=0.763) between Nivolumab and Regorafenib groups were also insignificant. Regarding TRAE incidence, the Nivolumab group was significantly lower than the Regorafenib group (37.5% vs 68%, p=0.006). After cession of nivolumab / regorafenib, 34 patients (37.8%) (Nivolumab group/ Regorafenib group: 11/23) could afford the following therapies. Concerning sequential systemic therapies, 17 patients (18.9%) received third-line therapy, whereas 6 patients (6.7%) could move to four-line therapy. In multivariable analysis, patients who achieved disease control were associated with improved OS (Hazard ratio, 0.18; 95% Confidence Interval, 0.07–0.46; p<0.001) after adjusting Child-Pugh class and Post-treatment. After sorafenib failure, using nivolumab had lower TRAE incidence and a trend of better treatment response than using regorafenib.

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Section: Discussionmentioning

confidence: 98%

Nivolumab vesus Regorafenib in patients with hepatocellular carcinoma after Sorafenib failure

Kuo

Yen

Chen

et al. 2021

Preprint

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“…The reason why cemiplimab, atezolizumab, avelumab, durvalumab have not been included in the guidelines for the treatment of HCC is that their efficacy and safety is not completely certain, and several trials are still ongoing (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). Nivolumab as a first-line treatment option compared with sorafenib is still under research, and nivolumab may become first-line treatment if the result is positive (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23); atezo+bev has potential as a first-line treatment for unresectable HCC; both avelumab and axitinib are known to be safe when administered as monotherapy; cemiplimab and durvalumab have also demonstrated effectiveness in ORR (30,33,35,37,40). With an increase in the number of clinical trails, cemiplimab, atezolizumab, avelumab and durvalumab may be added to the guidelines.…”

Section: Discussionmentioning

confidence: 99%

“…Nivolumab plus ipilimumab was evaluated in patients with advanced HCC pretreated with sorafenib. The ORR was 31%, disease control rate (DCR) was 49% and a median duration of response was 17 months ( 22 ). NCCN recommends nivolumab as a subsequent therapy following disease progression in patients with CPA (Child-Pugh class A) or CPB (Child-Pugh class B) disease (a category 2A recommendation) ( 23 ).…”

Section: Listed Drugsmentioning

confidence: 99%

Clinical outcomes and influencing factors of PD‑1/PD‑L1 in hepatocellular carcinoma (Review)

Wang

Tang

et al. 2021

Oncol Lett

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Hepatocellular carcinoma (HCC) has an increasing incidence worldwide, and the global 5-year survival rate ranges from 5-30%. In China, HCC seriously threatens the nation's health; the incidence of HCC ranks fourth among all theriomas, and the mortality rate is the third highest worldwide. The main therapies for HCC are surgical treatment or liver transplantation; however, most patients with HCC will experience postoperative recurrence or metastasis, eventually resulting in mortality. As for advanced or unresectable HCC, the current appropriate treatment strategy is transarterial chemoembolization; however, limited therapeutic effect and natural or acquired drug resistance affect the efficacy of this approach. Previous studies have demonstrated that PD-L1 expression on host cells and myeloid cells plays an important role in PD-L1 blocked-mediated tumor regression. Thus, further research on programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) is required. Countries including the United States, France, Britain and China have developed PD-1/PD-L1 blockers, including nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, toripalimab, sintilimab and camrelizumab. Notably, all of these blockers have therapeutic effect and influencing factors in HCC. Factors that influence the clinical outcome of PD-1 have also been discovered, such as inflammatory genes, specific receptors and signaling pathways. The discovery of these factors will help to identify novel methods, such as combination treatment, to decrease the influence of other factors on the efficacy of PD-1/PD-L1. Sorafenib and lenvatinib have been approved for first-line treatment for patients with advanced HCC. When first-line treatment frequently fails, pembrolizumab and ipilimumab plus nivolumab are used following sorafenib (but not lenvatinib) treatment in advanced HCC. Thus, tumor immunotherapy using PD-1/PD-L1 blockers exhibits promising outcomes for the treatment of HCC, and more novel PD-1/PD-L1 inhibitors are being developed to fight against this disease. The present review discusses the clinical results and influencing factors of PD-1/PD-L1 inhibitors in HCC to provide insight into the development and optimization of PD-1/PD-L1 inhibitors in the treatment of HCC. Contents 1. Introduction 2. Listed drugs 3. Listed drugs in China 4. Influencing factors 5. Discussion 6. Conclusions

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“… 25 Another real-world study compared the effectiveness of regorafenib (n=223) and nivolumab (n=150) after sorafenib failure and demonstrated that only one patient (0.7%) in the nivolumab group but none in the regorafenib group achieved a CR. 26 Joerger et al 27 presented the case of a sorafenib-refractory patient probably experiencing progressive disease during ICI combination treatment with the anti-PD-1 monoclonal antibody nivolumab and the anti-Glucocorticoid Induced Tumor Necrosis Factor Receptor (anti-GITR) monoclonal antibody BMS-986156 within a clinical phase-1 trial followed by a prolonged tumor response according to RECIST v 1.1 during third-line treatment with regorafenib. In this case, sorafenib-immunotherapy-regorafenib sequential treatment was applied and the last evaluation was documented as PR and the patient started taking regorafenib at a reduced dose of 80mg and later further reduced to 40mg per day.…”

Section: Discussionmentioning

confidence: 99%

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

Zhang¹,

Zhang²,

Li³

et al. 2020

OTT

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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.

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Regorafenib Versus Nivolumab After Sorafenib Failure: Real‐World Data in Patients With Hepatocellular Carcinoma

Cited by 34 publications

References 38 publications

Nivolumab vesus Regorafenib in patients with hepatocellular carcinoma after Sorafenib failure

Nivolumab vesus Regorafenib in patients with hepatocellular carcinoma after Sorafenib failure

Clinical outcomes and influencing factors of PD‑1/PD‑L1 in hepatocellular carcinoma (Review)

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

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