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The association of clinical outcome to first-line VEGF-targeted therapy with clinical outcome to second-line VEGF-targeted therapy in metastatic renal cell carcinoma patients.

ABSTRACT: There are many active drugs to treat metastatic renal cell carcinoma (mRCC) patients who progress through their first-line vascular endothelial growth factor (VEGF) inhibitor. Many clinicians choose a second-line VEGF inhibitor based on the type of response to first-line VEGF inhibitor, without data supporting this practice. This study was conducted to determine the association of response to second-line VEGF inhibitor with response to first-line VEGF inhibitor. All mRCC patients in participating centers of the International mRCC Database Consortium who were treated from January 2004 through June 2011 with a second-line VEGF inhibitor after failure of a different first-line VEGF inhibitor were retrospectively identified. The primary outcome is objective response rate (ORR) and the secondary outcome is progression-free survival (PFS) in each line of therapy. Of 1,602 total database patients, 464 patients received a first- and second-line VEGF inhibitor. The ORR to first-line therapy was 22%, and the ORR to second-line therapy was 11%. The ORR to second-line therapy was not different among patients achieving partial response versus stable disease versus progressive disease to first-line therapy (14% vs. 10% vs. 11%, respectively; chi-squared trend test p=0.17). The median PFS on first-line VEGF-targeted therapy was 7.5 months (95% CI, 6.6-8.1), and the median PFS on second-line VEGF inhibitor was 3.9 months (95% CI, 3.6-4.5). There was no correlation between first-line and second-line PFS (Pearson correlation coefficient 0.025; p=0.59). The clinical response to a second-line VEGF inhibitor is not dependent on response to the first-line VEGF-inhibitor. Further studies are needed to define clinical parameters that predict response to second-line therapy to optimize the sequence of VEGF-targeted therapy in metastatic RCC patients.

SUBMITTER: Al-Marrawi MY

PROVIDER: S-EPMC4144038 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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The association of clinical outcome to first-line VEGF-targeted therapy with clinical outcome to second-line VEGF-targeted therapy in metastatic renal cell carcinoma patients.

Al-Marrawi Mhd Y MY Rini Brian I BI Harshman Lauren C LC Bjarnason Georg G Wood Lori L Vaishampayan Ulka U MacKenzie Mary M Knox Jennifer J JJ Agarwal Neeraj N Al-Harbi Hulayel H Kollmannsberger Christian C Tan Min-Han MH Rha Sun Young SY Donskov Frede N FN North Scott S Choueiri Toni K TK Heng Daniel Y DY

Targeted oncology 20130109 3

There are many active drugs to treat metastatic renal cell carcinoma (mRCC) patients who progress through their first-line vascular endothelial growth factor (VEGF) inhibitor. Many clinicians choose a second-line VEGF inhibitor based on the type of response to first-line VEGF inhibitor, without data supporting this practice. This study was conducted to determine the association of response to second-line VEGF inhibitor with response to first-line VEGF inhibitor. All mRCC patients in participatin ...[more]

PMID: 23300029

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Project description:: Background: The optimal anti-angiogenic strategy as second-line treatment in RAS wild-type metastatic colorectal cancer (mCRC) treated with anti-EGFR (Epidermal Growth Factor Receptor) based first-line treatment is still debated. This multicenter, real-world, retrospective study is aimed at evaluating the effectiveness of second-line Bevacizumab- and Aflibercept-based treatments after an anti-EGFR based first-line regimen. Clinical outcomes measured were: objective response rate (ORR), progression free survival (PFS), overall survival (OS) and adverse events (AEs) profiles. From February 2011 to October 2019, 277 consecutive mCRC patients received Bevacizumab-based (228, 82.3%) or Aflibercept-based (49, 17.7%) regimen. No significant difference was found regarding ORR. The median follow-up was 27.7 months (95%CI: 24.7-34.4). Aflibercept-treated group had a significantly shorter PFS compared to Bevacizumab-treated group (5.6 vs. 7.1 months, respectively) (HR = 1.34 (95%CI: 0.95-1.89); p = 0.0932). The median OS of the Bevacizumab-treated group and Aflibercept-treated group was 16.2 (95%CI: 15.3-18.1) and 12.7 (95%CI: 8.8-17.5) months, respectively (HR= 1.31 (95%CI: 0.89-1.93) p = 0.16). After adjusting for the key covariates (age, gender, performance status, number of metastatic sites and primary tumor side) Bevacizumab-based regimens revealed to be significantly related with a prolonged PFS (HR = 1.44 (95%CI: 1.02-2.03); p = 0.0399) compared to Aflibercept-based regimens, but not with a prolonged OS (HR = 1.47 (95%CI: 0.99-2.17); p = 0.0503). The incidence of G3/G4 VEGF inhibitors class-specific AEs was 7.5% and 26.5% in the Bevacizumab-treated group and the Aflibercept-treated group, respectively (p = 0.0001). Our analysis seems to reveal that Bevacizumab-based regimens have a slightly better PFS and class-specific AEs profile compared to Aflibercept-based regimen as second-line treatment of RAS wild-type mCRC patients previously treated with anti-EGFR based treatments. These results have to be taken with caution and no conclusive considerations are allowed.

Project description:BackgroundIn 2006, the economic burden of metastatic renal cell carcinoma (mRCC) was estimated to be up to $1.6 billion worldwide and has since grown annually. With the continuing increase of the economic burden of this disease in the United States, there is a growing need for economic analyses to guide treatment and policy decisions for this patient population.ObjectiveTo evaluate available comparative economic data on targeted therapies for patients with mRCC who have failed first-line targeted therapies.MethodA broad and comprehensive literature review was conducted of US-based studies between January 1, 2005, and February 11, 2013, evaluating comparative economic evidence for targeted agents that are used as second-line therapy or beyond. Based on the specific search parameters that focused on cost-effectiveness and economic comparisons between vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFr) inhibitors and mammalian target of rapamycin (mTOR) inhibitors, only 7 relevant, US-based economic evaluations were found appropriate for inclusion in the analysis. All authors, who are experts in the health economics and outcomes research field, reviewed the search results. Studies of interest were those with a targeted agent, VEGF/VEGFr or mTOR inhibitor, in at least 1 study arm.DiscussionAs a group, targeted therapies were found to be cost-effective options in treating patients with refractory mRCC in the United States. Oral therapies showed an economic advantage over intravenous agents, presumably because oral therapies have a lower impact on outpatient resources. Based on 3 studies, everolimus has been shown to have an economic advantage over temsirolimus and to be cost-effective compared with sorafenib. No economic comparison between everolimus and axitinib, the only 2 drugs with a National Comprehensive Cancer Network category 1 recommendation for use after the failure of VEGFr tyrosine kinase inhibitors, is available.ConclusionThe limited and heterogeneous sum of the currently available economic evidence does not allow firm conclusions to be drawn about the most cost-effective targeted treatment option in the second-line setting and beyond in patients with mRCC. It is hoped that ongoing head-to-head therapeutic trials and biomarker studies will help improve the economic efficiency of these expensive agents.

Project description:ImportanceClinical trials have shown an overall survival (OS) benefit associated with first-line immunotherapy (IT) and combination targeted therapy (TT) and IT regimens compared with TT among patients with metastatic clear cell renal cell carcinoma (RCC). Generalizability of these findings in a real-world cohort outside of a clinical trial setting is unclear.ObjectiveTo assess the association of first-line TT, IT, and combination TT and IT regimens with OS in a real-world cohort of patients with metastatic clear cell RCC.Design, setting, and participantsThis retrospective propensity-matched cohort study identified 5872 patients with metastatic clear cell RCC in the National Cancer Database from January 1, 2015, to December 31, 2017, who received first-line TT, IT, or combination TT and IT and were not treated on a clinical trial protocol. Patients were stratified by first-line systemic treatment. Statistical analysis was conducted from October 1 to December 1, 2020.Main outcomes and measuresThe primary outcome was OS from the date of diagnosis to death or censoring at last follow-up. After 1:1:1 nearest-neighbor caliper matching of propensity scores, survival analyses were conducted using Cox proportional hazards regression and Kaplan-Meier estimates.ResultsThe final study population included 5872 patients (TT group: n = 4755 [81%]; 3332 men [70%]; median age, 64 years [interquartile range, 57-71 years]; IT group: n = 638 [11%]; 475 men [74%]; median age, 61 years [interquartile range, 54-69 years]; and combination TT and IT group: n = 479 [8%]; 321 men [67%]; median age, 62 years [interquartile range, 55-69 years]), and the matched cohort included 1437 patients (479 per treatment group). Patients in the IT and combination TT and IT groups were younger than those in the TT group, had fewer comorbid conditions (Charlson-Deyo score of 0, 480 of 638 [75%] in the TT group, 356 of 479 [74%] in the IT group, and 3273 of 4755 [69%] in the combination TT and IT group), and were more often treated at academic centers (315 of 638 [49%], 216 of 479 [45%], and 1935 of 4755 [41%], respectively). Both first-line IT and combination TT and IT were associated with improved OS compared with first-line TT for patients with metastatic clear cell RCC (IT group: hazard ratio [HR], 0.60 [95% CI, 0.48-0.75]; P < .001; combination TT and IT group: HR, 0.74 [95% CI, 0.60-0.91]; P = .005). No survival difference was seen between the IT and combination TT and IT groups (combination TT and IT: HR, 1.24 [95% CI, 0.98-1.56]; P = .08).Conclusions and relevanceThis study suggests that both first-line IT and combination TT and IT were associated with improved OS compared with first-line TT for patients with metastatic clear cell RCC. These findings are similar to those identified in recently reported clinical trials, lending confidence to the broader applicability of these findings outside of a clinical trial setting.

Dataset Information

The association of clinical outcome to first-line VEGF-targeted therapy with clinical outcome to second-line VEGF-targeted therapy in metastatic renal cell carcinoma patients.

Publications

The association of clinical outcome to first-line VEGF-targeted therapy with clinical outcome to second-line VEGF-targeted therapy in metastatic renal cell carcinoma patients.

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