Objective Response by mRECIST Is an Independent Prognostic Factor of Overall Survival in Systemic Therapy for Hepatocellular Carcinoma

Kudo, Masatoshi

doi:10.1159/000497460

Cited by 15 publications

(16 citation statements)

References 11 publications

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“…However, to date, criteria for their selection based on patients' characteristics have not been established. The response to multikinase inhibitors determines the prognosis of patients with unresectable HCC [8][9][10] ; optimizing drug selection is therefore of particular importance. We speculated that, because these two multikinase inhibitors have different kinase affinity profiles, it is possible that certain factors may be identified to aid in individualizing treatment.…”

Section: Discussionmentioning

confidence: 99%

“…According to recent reports, OR based on mRECIST is an independent prognostic factor for OS in patients receiving systemic therapy for unresectable HCC. 9 Therefore, in the lenvatinib group, those with OR (CR and PR) were defined as responders. As OR rates with sorafenib are lower than those with lenvatinib, 7 and the impact of long-SD on OS in those receiving sorafenib is similar to that of OR with sorafenib, 8 patients with SD for >6 months (long-SD) and PR/CR with sorafenib were considered responders; other patients were defined as nonresponders (nonresponder).…”

Section: Methodsmentioning

confidence: 99%

“…Reports suggest that the objective response (OR), evaluated by modified Response Evaluation Criteria in Solid Tumors (mRECIST), is an independent prognostic factor for OS with systemic therapy in these cases. [8][9][10] In addition, in patients receiving sorafenib for unresectable HCC, the impact of long-term stable disease (long-SD) on OS is similar to that of complete response (CR) and partial response (PR). 8 Various studies have analyzed the predictive factors of the treatment response to sorafenib in unresectable HCC.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, either multikinase inhibitor may be selected as first‐line therapy; however, criteria for their selection based on patient and tumor characteristics are unavailable. Reports suggest that the objective response (OR), evaluated by modified Response Evaluation Criteria in Solid Tumors (mRECIST), is an independent prognostic factor for OS with systemic therapy in these cases . In addition, in patients receiving sorafenib for unresectable HCC, the impact of long‐term stable disease (long‐SD) on OS is similar to that of complete response (CR) and partial response (PR) …”

Section: Introductionmentioning

confidence: 99%

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Baseline angiopoietin‐2 and FGF19 levels predict treatment response in patients receiving multikinase inhibitors for hepatocellular carcinoma

et al. 2020

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Background: Sorafenib and lenvatinib are first-line systemic therapies for unresectable hepatocellular carcinoma (HCC). However, the criteria for their selection remain unclear. Methods: We identified patients with unresectable HCC who were treated with sorafenib or lenvatinib between August 2009 and January 2019 at the Hokkaido University Hospital. Patients who continued treatment for >2 months, underwent evaluation by computed tomography every 2-3 months, and had complete clinical data were included. Responders were patients with objective response (OR) for lenvatinib and patients with stable disease (SD) exceeding 6 months (long-SD) or OR for sorafenib. The predictive factors for treatment response, including fibroblast growth factor (FGF)19 and 21, angiopoietin 2 (ANG2), hepatocyte growth factor, and vascular endothelial growth factor, were evaluated. Results: Overall, 27 and 29 patients treated with lenvatinib and sorafenib, respectively, were included. The responders for lenvatinib and sorafenib were 63% (17/27) and 38% (11/29), respectively. No significant predictive factors for treatment response were identified in patients treated with sorafenib. However, baseline serum FGF19 and ANG2 levels were significantly associated with treatment response to lenvatinib. All (9/9) patients with low baseline ANG2 and FGF19 levels who received lenvatinib achieved OR. Conversely, the OR was low (13%; 1/9) in patients with high baseline ANG2 and FGF19 levels. Responder rate was 40% (2/5) in patients with high baseline ANG2 and FGF19 levels who received sorafenib. Conclusion: This study is, to our knowledge, the first to demonstrate that baseline ANG2 and FGF19 levels may aid in selecting optimal systemic therapy for patients with unresectable HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Baseline angiopoietin‐2 and FGF19 levels predict treatment response in patients receiving multikinase inhibitors for hepatocellular carcinoma

et al. 2020

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“…Therefore, even after PD following anti-PD-1/PD-L1 therapy, subsequent treatment with an MTA will change the tumor microenvironment (TME) from immune suppressive to immune permissive, resulting in a favorable TME similar to that Table 10. Age distribution in patients with unresectable HCC in positive phase 3 trials Trial SHARP [4] Asia-Pacific [5] REFLECT [16] RESORCE [25] REACH [22] REACH (Japanese) [ All cohort: 32 (14) 208 (44) 193 (41) Overall 258 (45) 133 (47) 120 4324 5326 (54) Trial REACH-2 [29] REACH-2 (Japan) [66] CELESTIAL [28] IMbrave150 [19] CheckMate 459 [17] KEYNOTE-240 [30] ramucirumab 113 (48) 158 4787 (53) 186 (50) 196 (53) All cohort: 240 (58) HCC, hepatocellular carcinoma; na, not available. * Median (range).…”

Section: Possible Sequential Systemic Therapymentioning

confidence: 99%

Recent Advances in Systemic Therapy for Hepatocellular Carcinoma in an Aging Society: 2020 Update

Kudo¹

2020

Liver Cancer

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Systemic therapy for hepatocellular carcinoma (HCC) has changed markedly since the introduction of the molecular targeted agent sorafenib in 2007. Sorafenib increased the available treatment options for patients with extrahepatic spread and vascular invasion and improved survival in patients with advanced HCC; however, various shortcomings such as low response rates and relatively high toxicity (e.g., hand-foot skin reaction) prompted concerted efforts aimed at developing new molecular targeted agents to provide more treatment options and second-line agents for patients with disease progression or intolerance to sorafenib. Despite many attempts to develop new drugs between 2007 and 2016, all first-line and second-line clinical trials conducted during this period failed. However, between 2017 and 2019, 4 drugs (lenvatinib as a first-line agent and regorafenib, cabozantinib, and ramucirumab as second-line agents) emerged in quick succession from clinical trials and became available for clinical use. In addition, nivolumab and pembrolizumab were approved as second-line agents after sorafenib. A recent phase III trial (IMbrave150) showed that combination immunotherapy with atezolizumab plus bevacizumab increases overall survival compared with sorafenib therapy; Food and Drug Agency already approved this combination therapy, and worldwide approval is expected soon. This review describes the recent advances in systemic therapy and the use of tyrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib, and cabozantinib), monoclonal antibodies (ramucirumab and bevacizumab), and immune checkpoint inhibitors (nivolumab, pembrolizumab, and atezolizumab) in elderly patients and the similarity of their efficacy and safety profiles to those in the general population.

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Assessment of pegylated arginine deiminase and modified FOLFOX6 in patients with advanced hepatocellular carcinoma: Results of an international, single‐arm, phase 2 study

Harding

Yang

Chen

et al. 2021

Cancer

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BACKGROUND: Arginine starvation depletes the micronutrients required for DNA synthesis and interferes with both thymidylate synthetase activity and DNA repair pathways in preclinical models of hepatocellular carcinoma (HCC). Pegylated arginine deiminase (ADI-PEG 20), an arginine degrader, potentiates the cytotoxic activity of platinum and pyrimidine antimetabolites in HCC cellular and murine models. METHODS: This was a global, multicenter, open-label, single-arm, phase 2 trial of ADI-PEG 20 and modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) in patients who had HCC with Child-Pugh A cirrhosis and disease progression on ≥2 prior lines of treatment. The primary objective was the objective response rate assessed according to Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary objectives were to estimate progression-free survival, overall survival, safety, and tolerability. Eligible patients were treated with mFOLFOX6 intravenously biweekly at standard doses and ADI-PEG-20 intramuscularly weekly at 36 mg/m 2 . RESULTS: In total, 140 patients with advanced HCC were enrolled. The median patient age was 62 years (range, 30-85 years), 83% of patients were male, 76% were of Asian race, 56% had hepatitis B viremia, 10% had hepatitis C viremia, 100% had received ≥2 prior lines of systemic therapy, and 39% had received ≥3 prior lines of systemic therapy. The objective response rate was 9.3% (95% confidence interval [CI], 5.0%-15.4%), with a median response duration of 10.2 months (95% CI, 5.8 months to not reached). The median progressionfree survival was 3.8 months (95% CI, 1.8-6.3 months), and the median overall survival was 14.5 months (95% CI, 13.6-20.9 months). The most common grade ≥3 treatment-related events were neutropenia (32.9%), white blood cell count decrease (20%), platelet count decrease (19.3%), and anemia (9.3%). CONCLUSIONS: Concurrent mFOLFOX6 plus ADI-PEG 20 exhibited limited antitumor activity in patients with treatment-refractory HCC. The study was terminated early, and no further evaluation of the combination will be pursued.

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Objective Response by mRECIST Is an Independent Prognostic Factor of Overall Survival in Systemic Therapy for Hepatocellular Carcinoma

Cited by 15 publications

References 11 publications

Baseline angiopoietin‐2 and FGF19 levels predict treatment response in patients receiving multikinase inhibitors for hepatocellular carcinoma

Baseline angiopoietin‐2 and FGF19 levels predict treatment response in patients receiving multikinase inhibitors for hepatocellular carcinoma

Recent Advances in Systemic Therapy for Hepatocellular Carcinoma in an Aging Society: 2020 Update

Assessment of pegylated arginine deiminase and modified FOLFOX6 in patients with advanced hepatocellular carcinoma: Results of an international, single‐arm, phase 2 study

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