Comparison of the Clinical Outcome of Ramucirumab for Unresectable Hepatocellular Carcinoma with That of Prior Tyrosine Kinase Inhibitor Therapy

Oncology ◽  
2021 ◽  
Vol 99 (5) ◽  
pp. 327-335
Author(s):  
Kei Amioka ◽  
Tomokazu Kawaoka ◽  
Yutaro Ogawa ◽  
Chihiro Kikukawa ◽  
Kensuke Naruto ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Outcome ◽  
Tyrosine Kinase ◽  
Disease Control ◽  
Tyrosine Kinase Inhibitor ◽  
Treatment Response ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
Unresectable Hepatocellular Carcinoma

Introduction: The clinical outcome of ramucirumab in multi-molecular targeted agent (MTA) sequential therapy for unresectable hepatocellular carcinoma (u-HCC) was assessed in comparison with that of prior tyrosine kinase inhibitor (TKI) therapy. Methods: Sixteen patients who received ramucirumab as part of multi-MTA sequential therapy for u-HCC were enrolled in a retrospective, cohort study. Ramucirumab was started as 2nd line in 7 patients, 3rd line in 5 patients, and 4th line in 4 patients. Results: The overall response rate was 6.3%, the disease control rate (DCR) was 50.0%, median progression-free survival was 2.0 months (evaluated by mRECIST), median overall survival (OS) with ramucirumab was 7.9 months, and the median OS from 1st-line therapy was 28.1 months. One month after the start of ramucirumab, α-fetoprotein (AFP) decreased in 6 of 12 cases (50.0%), and the DCR in AFP-decreased cases was 83.3%. The DCR of ramucirumab was 66.7% in cases in which disease control was obtained by prior TKI therapy, whereas it was 0.0% in the cases in which disease control was not obtained by prior TKI therapy. Examining the adverse events, no new safety concerns were confirmed. Conclusion: The AFP response to ramucirumab and the treatment response to prior TKI therapy are associated with treatment response to ramucirumab.

Clinical Outcomes of 2nd- and 3rd-Line Regorafenib for Advanced Hepatocellular Carcinoma

Oncology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Kensuke Naruto ◽  
Tomokazu Kawaoka ◽  
Kei Amioka ◽  
Yutaro Ogawa ◽  
Kikukawa Chihiro ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Outcomes ◽  
Median Overall Survival ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Free Survival ◽  
Line Therapy ◽  
Unresectable Hepatocellular Carcinoma

<b><i>Introduction:</i></b> This study compared clinical outcomes of 2nd- and 3rd-line regorafenib in patients with unresectable hepatocellular carcinoma. <b><i>Methods:</i></b> In this retrospective cohort study, 48 patients were treated with regorafenib for unresectable hepatocellular carcinoma. Thirty-five and 13 patients were initiated on 2nd- and 3rd-line therapy, respectively. We assessed the responses to and safety of the therapy. <b><i>Results:</i></b> There were no statistically significant differences in clinical characteristics at the start of 2nd- or 3rd-line regorafenib therapy. The overall response rate of 2nd- and 3rd-line regorafenib was 20 and 8%, respectively. The disease control rate was 57 and 54%, respectively. Median overall survival (mOS) from the start of 2nd-line regorafenib was 17.5 months. mOS from the start of 3rd-line regorafenib was not obtained. Median progression-free survival of 2nd- and 3rd-line regorafenib was 4.9 and 2.3 months, respectively. mOS from 1st-line therapy with tyrosine kinase inhibitor plus sorafenib-regorafenib-lenvatinib was 29.5 months; that with lenvatinib-sorafenib-regorafenib was not obtained. Patients on 3rd-line therapy tended to have better Child-Pugh scores and tumor factors at the start of 1st-line therapy than other patients. <b><i>Conclusion:</i></b> Patients on 2nd- and 3rd-line regorafenib showed favorable responses. Good Child-Pugh scores and tumor factors may be associated with a better response rate and OS.

DNA damage repair (DDR) pathway alteration in advanced renal cell carcinoma (RCC) is association with good progression-free survival with tyrosine kinase inhibitor (TKI) therapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 346-346
Author(s):  
Wei Zhai ◽  
Junyun Wang ◽  
Ning He ◽  
Jiale Zhou ◽  
Jianfei Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Vascular Endothelial ◽  
Damage Repair ◽  
Endothelial Growth Factor

346 Background: Alterations in DNA damage repair (DDR) genes are associated with human tumorigenesis and may be as potential biomarkers for vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy in renal cell carcinoma. However, biologic significance and relevance to TKI targeted therapy in metastatic RCC are unknown. Methods: Genomic data and treatment outcomes were retrospectively collected for patients with metastatic RCC. Tumor and germline DNA were subject to targeted next generation sequencing across 642 genes of interest, including 60 DDR genes. Patients were dichotomized according to underlying DDR gene alteration into (1) DDR gene alterations present (Mut DDR); (2) wildtype (WT) DDR gene alterations present (WT DDR). Association between DDR status and therapeutic benefit was investigated separately for and vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy. Results: Mut DDR were detected in 17/40 patients (42.5%). The most frequently DDR altered genes were TP53. For patients with TKI treatment, Mut DDR status was associated with superior progression free survival (log-rank p = 0.048), but not with superior overall survival (log-rank p = 0.39); after adjusting for International Metastatic Renal Cell Carcinoma Database Consortium risks and extent of prior therapy, the HR for Mut DDR was 2.68 (95% CI: 0.96–7.46; p = 0.059). Conclusions: DDR alterations are recurrent genomic events in patients with advanced RCC and were mostly clonal in this cohort. Dysfunction events in these genes may affect outcome with TKI therapy in adanced RCC, and these hypothesis-generating results deserve further study.

WE-C-BRC-05: Use of FLT PET Imaging to Assess Tyrosine Kinase Inhibitor (TKI) Treatment Response

2009 ◽  
Vol 36 (6Part24) ◽  
pp. 2761-2761
Author(s):  
R Jeraj ◽  
M Vanderhoek ◽  
U Simoncic ◽  
S Perlman ◽  
D Alberti ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Treatment Response ◽  
Pet Imaging ◽  
Kinase Inhibitor ◽  
Flt Pet ◽  
Tki Treatment
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