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Encouraging efficacy of a comprehensive therapy consisting of sintilimab, bevacizumab biosimilar IBI305, hypo-fractionated intensity-modulated radiotherapy, and oxaliplatin for a maxillary metastasis from hepatocellular carcinoma: A case report and literature review.

ABSTRACT: Oro-maxillo-facial metastasis from hepatocellular carcinoma (HCC) is very rare, and reports on treating maxillary metastasis from HCC are unavailable. Anti-angiogenesis therapy combined with immunotherapy represented by programmed cell death 1 (PD-1) or its ligand (PD-L1) inhibitor has become the standard treatment of advanced HCC. However, integrating chemoradiotherapy into immunotherapy-bevacizumab combination therapy has not been reported. Here, we presented a Chinese woman with maxillary metastasis from HCC who achieved a nearly complete response (CR) to a quadruple treatment scheme consisting of a PD-1 monoclonal antibody (sintilimab), bevacizumab biosimilar IBI305, hypo-fractionated intensity-modulated radiotherapy (hfIMRT), and concurrent oxaliplatin. This comprehensive treatment is an innovative and effective therapy for advanced HCC.

SUBMITTER: Liang X

PROVIDER: S-EPMC9727184 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Encouraging efficacy of a comprehensive therapy consisting of sintilimab, bevacizumab biosimilar IBI305, hypo-fractionated intensity-modulated radiotherapy, and oxaliplatin for a maxillary metastasis from hepatocellular carcinoma: A case report and literature review.

Liang Xuexia X Liu Qiaodan Q Yao Wei W Zhu Shuqin S

Frontiers in oncology 20221123

Oro-maxillo-facial metastasis from hepatocellular carcinoma (HCC) is very rare, and reports on treating maxillary metastasis from HCC are unavailable. Anti-angiogenesis therapy combined with immunotherapy represented by programmed cell death 1 (PD-1) or its ligand (PD-L1) inhibitor has become the standard treatment of advanced HCC. However, integrating chemoradiotherapy into immunotherapy-bevacizumab combination therapy has not been reported. Here, we presented a Chinese woman with maxillary met ...[more]

PMID: 36505782

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Project description:Abstract High-producing cell line could improve the affordability and availability of biotherapeutic products. A post-approval production cell line change, low-titer CHO-K1S to high-titer CHO-K1SV GS-KO, was performed for a China marketed bevacizumab biosimilar IBI305. Currently, there is no regulatory guideline specifically addressing the requirements for comparability study of post-approval cell line change, which is generally regarded as the most complex process change for biological products. Following the quality by design principle and risk assessment, an extensive analytical characterization and three-way comparison was performed by using a panel of advanced analytical methods. Orthogonal and state-of-the-art techniques including nuclear magnetic resonance and high-resolution mass spectrometry were applied to mitigate the potential uncertainties of higher-order structures and to exclude any new sequence variants, scrambled disulfide bonds, glycan moiety and undesired process-related impurities such as host cell proteins. Nonclinical and clinical pharmacokinetics (PK) studies were conducted subsequently to further confirm the comparability. The results demonstrated that the post-change IBI305 was analytically comparable to the pre-change one and similar to the reference product in physicochemical and biological properties, as well as the degradation behaviors in accelerated stability and forced degradation studies. The comparability was further confirmed by comparable PK, pharmacodynamics, toxicological and immunogenicity profiles of nonclinical and clinical studies. The comparability strategy presented here might extend to cell line changes of other post-approval biological products, and particularly set a precedent in China for post-approval cell line change of commercialized biosimilars. Statement of Significance: Our work represents the first report of comparability exercise for the post-approval production cell line change, following a QbD approach with tier-based quality attribute evaluation and risk assessment. The state-of-the-art and orthogonal techniques were applied and demonstrated the comparable structural and functional characterizations, which were further confirmed by nonclinical and clinical PK profiles.

Project description:BackgroundProgrammed cell death protein 1 (PD-1) or its ligand (PD-L1) monoclonal antibody combined with bevacizumab (a monoclonal antibody targeting vascular endothelial growth factor) has been established as first-line systemic treatment for advanced hepatocellular carcinoma (HCC). Radiotherapy is a crucial local treatment for HCC. Mutual efficacy enhancement has been reported between radiotherapy, anti-angiogenesis therapy and immunotherapy in preclinical researches, but not been validated in clinical practice. Whether radiotherapy can enhance efficacy of anti-PD-1 immunotherapy plus bevacizumab for HCC remains unclear. This retrospective observational study aimed to appraise efficacy and safety of the combination of radiotherapy with pembrolizumab (a PD-1 monoclonal antibody) and bevacizumab for advanced HCC for the first time.MethodsPatients with advanced HCC treated by intrahepatic tumor-directed moderately hypo-fractionated radiotherapy combined with pembrolizumab and bevacizumab were consecutively included. Clinicopathological characteristics, therapeutic outcomes and treatment-related adverse events (TRAEs) were recorded and evaluated.ResultsA total of 23 patients were eventually enrolled. Median cycles of pembrolizumab and bevacizumab were 4 (median, 1-8) and 4 (median, 1-9) cycles. The objective response rates and disease control rates of irradiated intrahepatic HCC and non-irradiated extrahepatic HCC were 34.8% [95% confidence interval (CI), 16.4-57.3%] vs. 10.0% (95% CI, 1.2-31.7%), and 91.3% (95% CI, 72.0-98.9%) vs. 70.0% (95% CI, 45.7-88.1%), respectively. The median progression-free survival (PFS) and overall survival (OS) were 6.6 (95% CI, 4.7-8.5) and 18.3 (95% CI, 8.2-33.6) months, and 12-month PFS and OS rates were 17.5% (95% CI, 7.0-28.0%) and 60.9% (95% CI, 50.7-71.1%). Two patients (8.7%) with locally advanced, unresectable HCC eventually underwent curative resection of tumors after this trimodal treatment. Eighteen patients (78.3%) had ≥ grade 3 TRAEs, with myelosuppression and transaminase increase as the most common.ConclusionsThis study firstly reported that combining radiotherapy with pembrolizumab and bevacizumab was preliminarily a feasible and effective therapeutic choice for advanced HCC in despite of more TRAEs. This tri-modal regimen may be a potential conversion therapy for unresectable, locally advanced HCC. The limitations of this study are its retrospective nature and small sample size; therefore, big-sample prospective studies are warranted to further investigate this tri-modal regimen.

Project description:BackgroundIn recent years, programmed cell death protein-1 inhibitors, including sintilimab, have significantly prolonged the overall survival time of patients with unresectable or metastatic hepatocellular carcinoma (HCC); however, the cost-effectiveness of sintilimab is unclear. The aim of this study was to assess the cost-effectiveness of sintilimab plus bevacizumab biosimilar compared with lenvatinib as first-line treatment in patients with unresectable or metastatic HCC.MethodsA lifetime partitioned survival model was developed to conduct a cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar vs. lenvatinib for advanced HCC from a Chinese healthcare system perspective. The clinical and safety data were derived from two recent randomized clinical trials, the ORIENT-32 and REFLECT studies. Utility data were obtained from previous studies. Long-term direct medical costs and quality-adjusted life-years (QALYs) were predicted. Deterministic and probabilistic sensitivity analyses were performed to verify the robustness of the model.ResultsCompared with lenvatinib, combination therapy with sintilimab and bevacizumab biosimilar yielded an additional 0.493 QALYs at a higher cost ($33,102 vs. $21,037) (2021 US dollars). This resulted in a deterministic incremental cost-effectiveness ratio (ICER) of $24,462 per QALY in the base-case analysis. The ICERs were sensitive to the utility of post-progression and the cost of bevacizumab biosimilar. A lower ICER was estimated when the dose of bevacizumab biosimilar decreased from 15 mg to 7.5 mg per kilogram in the scenario analysis. In the probabilistic sensitivity analysis, the probability of being cost-effective for sintilimab treatment at willingness-to-pay (WTP) thresholds of one ($12,516) and three times the gross domestic product per capita in China ($37,547) were 11.6% and 88.6%, respectively.ConclusionSintilimab plus bevacizumab biosimilar is likely to be a cost-effective treatment option as a first-line treatment for unresectable or metastatic HCC in China when WTP threshold is over $23,650.

Dataset Information

Encouraging efficacy of a comprehensive therapy consisting of sintilimab, bevacizumab biosimilar IBI305, hypo-fractionated intensity-modulated radiotherapy, and oxaliplatin for a maxillary metastasis from hepatocellular carcinoma: A case report and literature review.

Publications

Encouraging efficacy of a comprehensive therapy consisting of sintilimab, bevacizumab biosimilar IBI305, hypo-fractionated intensity-modulated radiotherapy, and oxaliplatin for a maxillary metastasis from hepatocellular carcinoma: A case report and literature review.

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