Comparative efficacy of vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin (mTOR) inhibitor as second-line therapy in patients with metastatic renal cell carcinoma after the failure of first-line VEGF TKI

2012 ◽  
Vol 29 (5) ◽  
pp. 3291-3297 ◽  
Author(s):  
Kwonoh Park ◽  
Jae-Lyun Lee ◽  
Inkeun Park ◽  
Seongjoon Park ◽  
Yongcheol Ahn ◽  
...  
Keyword(s):  
Mtor Inhibitor ◽  
Kinase Inhibitor ◽  
Mammalian Target Of Rapamycin ◽  
Vascular Endothelial ◽  
Second Line ◽  
Comparative Efficacy ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Endothelial Growth Factor

Comparative effectiveness of first-line VEGF TKI followed by second-line therapy with either a VEGF TKI or an mTOR inhibitor in patients with metastatic renal cell carcinoma.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 495-495
Author(s):  
Shiven B. Patel ◽  
Srinivas Kiran Tantravahi ◽  
David Gill ◽  
Austin Poole ◽  
Joseph Merriman ◽  
...  
Keyword(s):  
Mtor Inhibitor ◽  
Mtor Inhibitors ◽  
Vascular Endothelial ◽  
First Line ◽  
Second Line Therapy ◽  
Disease Characteristics ◽  
Line Therapy ◽  
Kaplan Meier ◽  
Factor Inhibitor ◽  
Endothelial Growth Factor

495 Background: In the INTORSECT trial, not progression-free (PFS), but overall survival (OS) was higher with sorafenib vs. temsirolimus in 2nd setting after 1st sunitinib therapy. Here, we compare the PFS and OS between any vascular endothelial growth factor inhibitor (VEGF TKI) and mTOR inhibitors (mTORi) in 2nd setting in mRCC after progression on 1st VEGF TKI. Methods: Pts were identified from an institutional database. Survival estimates of PFS and OS were assessed from initiation of 2nd therapy by Kaplan-Meier methodology and stratified by the median PFS of the 1st therapy. Results: Of 142 pts, 66 received a VEGF TKI (n=24, 36%) or an mTORi (n=42, 64%) in 2nd setting. Pts and disease characteristics with corresponding outcomes are presented in the table. Conclusions: A trend for improved PFS and OS was found with 2nd therapy with a VEGF TKI over an mTORi. Longer OS with 2nd VEGF TKI was seen in those on 1st VEGF TKI <8 months suggesting that continued VEGF inhibition may be a reasonable strategy in these pts. Data need to be validated in a larger cohort. [Table: see text]

scholarly journals Evaluation of second line and subsequent targeted therapies in metastatic renal cell cancer (mRCC) patients treated with first line cediranib

2014 ◽  
Vol 8 (11-12) ◽  
pp. 398 ◽  
Author(s):  
Suzanne Richter ◽  
Jo-An Seah ◽  
Gregory R Pond ◽  
Hui K Gan ◽  
Mary J. Mackenzie ◽  
...  
Keyword(s):  
Renal Cell ◽  
Kinase Inhibitor ◽  
Cell Cancer ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Pivotal Phase ◽  
Line Therapy ◽  
To Receive

Introduction: Pivotal phase III trials have positioned angiogenesis inhibitors as first-line therapy for the management of most advanced or metastatic renal cell carcinomas (mRCC). Approaches to second-line therapy, however, remain more controversial with respect to drug selection and drug sequencing.Methods: In this study we evaluated mRCC patients who were initially treated on the first-line National Cancer Institute (NCI) trial with the highly potent vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI), cediranib, to determine the efficacy and tolerability of subsequent therapies.Results: Twenty-eight (65.1%) of the 43 patients enrolled on the first-line cediranib trial were known to receive second-line therapy, most commonly sunitinib (n = 21), with 4 (14%), 2 (7%) and 1 (3%) patients receiving temsirolimus, sorafenib, and interleukin, respectively. Of these, 14 (50%) went on to have 3 or more lines of therapy. The progression-free survival (PFS) proportion (PFS) at 1 year from starting second line was 30% (14.5%–47.9%). Longer duration of first-line cediranib treatment was modestly associated with longer duration of second-line treatment (Spearman rho 0.26). Patients who discontinued cediranib for toxicity were less likely to receive second-line sunitinib.Conclusion: In this real world evaluation, sequential use of TKIs for the management of mRCC was common. PFS with sequential TKIs was similar to observed and published results for any second-line therapy. Prior toxicity affected treatment patterns and the frequent use of at least 3 lines of therapy underscores the need for prospective sequencing trials in this disease.

scholarly journals Pazopanib as first-line therapy for patients with metastatic kidney cancer

2018 ◽  
pp. 70-76
Author(s):  
B. Ya. Alekseev ◽  
I. M. Shevchuk
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Vascular Endothelial ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Endothelial Growth Factor

Pazopanib (Votrient®) is an oral small-molecule multi-kinase inhibitor that predominantly inhibits vascular endothelial growth factor receptor-1, -2 and -3, platelet-derived growth factor receptor-α and -β and the stem cell factor receptor c-Kit. In preliminary experiments using mouse and rabbit models of angiogenesis, pazopanib inhibited angiogenesis caused by a combined vascular endothelial growth factor and a major fibroblast growth factor. Although the drug was developed as a therapeutic multi-tumour agent, it is currently approved in many countries for the treatment of advanced soft tissue sarcoma and renal cell carcinoma (RCC). In multicentre, randomized trials of the efficacy of pazopanib as a first-line therapy in patients with metastatic RCC, progression-free survival (PFS) was significantly greater in pazopanib recipients than in cytokine recipients and pazopanib was noninferior to sunitinib with respect to time to disease progression. In addition, side effects such as liver dysfunction and hypertension can be usually managed, and pazopanib is likely to be a more preferred cost-effective option and shows better quality-of-life compared to other alternative drugs.

scholarly journals Outcomes from second-line therapy in long-term responders to first-line tyrosine kinase inhibitor in clear-cell metastatic renal cell carcinoma

2015 ◽  
Vol 26 (2) ◽  
pp. 378-385 ◽  
Author(s):  
R. Elaidi ◽  
A. Harbaoui ◽  
B. Beuselinck ◽  
J.-C. Eymard ◽  
A. Bamias ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Clear Cell ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy

A Rational Sequencing of Anti-Angiogenic Agents as Second-Line Treatment Choice for mCRC Patients Progressing After a Bevacizumab-Based First Line

2020 ◽  
pp. 14-19
Author(s):  
Sara De Dosso
Keyword(s):  
Acquired Resistance ◽  
Predictive Biomarker ◽  
Cancer Therapies ◽  
Vascular Endothelial ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Vegf Pathway ◽  
Effective Choice ◽  
Endothelial Growth Factor

A large proportion of patients with metastatic colorectal cancer (mCRC) experience disease progression after first-line treatment with chemotherapy and bevacizumab, an anti-angiogenic agent, as a result of acquired resistance. However, blocking angiogenesis by targeted therapy towards the vascular endothelial growth factor (VEGF) pathway still forms an essential part of the second-line treatment strategy. Although three approved evidence-based choices for angiogenic agents (continuing treatment with bevacizumab, ramucirumab and aflibercept) are currently available in the second line, making the most effective choice is challenging due to the lack of studies directly comparing these agents. Moreover, despite huge investigational efforts, no predictive biomarker for anti-angiogenic cancer therapies could be identified so far.

Efficacy and Toxicity of Addition of Bevacizumab to Chemotherapy in Patients with Metastatic Colorectal Cancer

2019 ◽  
Vol 21 (10) ◽  
pp. 718-724 ◽  
Author(s):  
Wen-Cong Ruan ◽  
Yue-Ping Che ◽  
Li Ding ◽  
Hai-Feng Li
Keyword(s):  
Colorectal Cancer ◽  
Adverse Event ◽  
Metastatic Colorectal Cancer ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Clinical Prognosis ◽  
Line Therapy ◽  
Significant Difference

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy. Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

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