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Risk of treatment-related deaths with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a meta-analysis of 41 randomized controlled trials.

Hong S, Fang W, Liang W, Yan Y, Zhou T, Qin T, Wu X, Ma Y, Zhao Y, Yang Y, Hu Z, Xue C, Hou X, Chen Y, Huang Y, Zhao H, Zhang L - Onco Targets Ther (2014)

Bottom Line: On subgroup analysis, significantly increased risk of death was found in patients with nonsmall-cell lung cancer (OR: 2.37; 95% CI: 1.19-4.73; P=0.01) and colorectal cancer (OR: 2.84; 95% CI: 1.02-7.96; P=0.05).Among different VEGFR-TKIs, sorafenib and sunitinib had significant risk of death when compared with control arms, respectively.The present work pointed out a significantly increased risk of death due to VEGFR-TKIs.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.

ABSTRACT

Background: Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have widely been used in advanced cancer. However, these drugs may also lead to serious adverse events. The present meta-analysis aimed to determine the overall incidence and risk of deaths due to VEGFR-TKIs with more detailed subgroup analysis.

Materials and methods: PubMed, Web of Science, and Cochrane databases were searched for randomized controlled trials (RCTs) that compared VEGFR-TKIs with non-VEGFR-TKIs in the treatment of solid cancer. Pooled incidence, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included trials.

Results: A total of 14,139 participants from 41 RCTs were enrolled. The pooled incidence of death due to VEGFR-TKIs was 1.9% (95% CI: 1.6%-2.3%) with an OR of 1.85 (95% CI: 1.33-2.58; P<0.01) when compared with control groups. On subgroup analysis, significantly increased risk of death was found in patients with nonsmall-cell lung cancer (OR: 2.37; 95% CI: 1.19-4.73; P=0.01) and colorectal cancer (OR: 2.84; 95% CI: 1.02-7.96; P=0.05). Among different VEGFR-TKIs, sorafenib and sunitinib had significant risk of death when compared with control arms, respectively. VEGFR-TKIs in combination with other antineoplastic agents, but not VEGFR-TKI monotherapy, significantly increased the risk of treatment-related deaths. No heterogeneity was noted across all the prespecified subgroups regarding ORs.

Conclusion: The present work pointed out a significantly increased risk of death due to VEGFR-TKIs. Close monitoring should be emphasized in patients receiving these drugs.

No MeSH data available.


Related in: MedlinePlus

Forest plot of the odds ratio for death events with VEGFR-TKIs: cumulative analysis in the order of publication years.Abbreviations: MH, Mantel–Haenszel; CI, confidence interval; VEGFR-TKIs, vascular endothelial growth factor receptor tyrosine kinase inhibitors.
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f3-ott-7-1851: Forest plot of the odds ratio for death events with VEGFR-TKIs: cumulative analysis in the order of publication years.Abbreviations: MH, Mantel–Haenszel; CI, confidence interval; VEGFR-TKIs, vascular endothelial growth factor receptor tyrosine kinase inhibitors.

Mentions: In order to explore the specific contribution of VEGFR-TKIs to the occurrence of TRDs, we determined the ORs of VEGFR-TKI-related deaths. As shown in Figure 2, a total of 12,313 patients from 32 RCTs were available to calculate the ORs of deaths due to VEGFR-TKIs. Using a fixed-effects model (heterogeneity test: Q-value =18.95; P=0.96; I2=0.0%), the combined OR was 1.85 (95% CI: 1.33–2.58; P<0.01). To examine the stability of the pooled OR, we performed a sensitivity analysis by sequentially removing individual studies. The results indicated that no single trial remarkably altered the pooled OR (Figure S2). Also, we performed a cumulative meta-analysis according to the publication years of the included trials. A consistent, statistically significant risk of TRDs was achieved in 2010 (OR: 2.30; 95% CI: 1.13–4.67; P=0.02) after only seven trials involving 3,545 patients had been included. Subsequently, 25 trials that enrolled an additional 8,768 patients until 2014 had little or no effect on the OR, but it simply narrowed the 95% CI (Figure 3).


Risk of treatment-related deaths with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a meta-analysis of 41 randomized controlled trials.

Hong S, Fang W, Liang W, Yan Y, Zhou T, Qin T, Wu X, Ma Y, Zhao Y, Yang Y, Hu Z, Xue C, Hou X, Chen Y, Huang Y, Zhao H, Zhang L - Onco Targets Ther (2014)

Forest plot of the odds ratio for death events with VEGFR-TKIs: cumulative analysis in the order of publication years.Abbreviations: MH, Mantel–Haenszel; CI, confidence interval; VEGFR-TKIs, vascular endothelial growth factor receptor tyrosine kinase inhibitors.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199796&req=5

f3-ott-7-1851: Forest plot of the odds ratio for death events with VEGFR-TKIs: cumulative analysis in the order of publication years.Abbreviations: MH, Mantel–Haenszel; CI, confidence interval; VEGFR-TKIs, vascular endothelial growth factor receptor tyrosine kinase inhibitors.
Mentions: In order to explore the specific contribution of VEGFR-TKIs to the occurrence of TRDs, we determined the ORs of VEGFR-TKI-related deaths. As shown in Figure 2, a total of 12,313 patients from 32 RCTs were available to calculate the ORs of deaths due to VEGFR-TKIs. Using a fixed-effects model (heterogeneity test: Q-value =18.95; P=0.96; I2=0.0%), the combined OR was 1.85 (95% CI: 1.33–2.58; P<0.01). To examine the stability of the pooled OR, we performed a sensitivity analysis by sequentially removing individual studies. The results indicated that no single trial remarkably altered the pooled OR (Figure S2). Also, we performed a cumulative meta-analysis according to the publication years of the included trials. A consistent, statistically significant risk of TRDs was achieved in 2010 (OR: 2.30; 95% CI: 1.13–4.67; P=0.02) after only seven trials involving 3,545 patients had been included. Subsequently, 25 trials that enrolled an additional 8,768 patients until 2014 had little or no effect on the OR, but it simply narrowed the 95% CI (Figure 3).

Bottom Line: On subgroup analysis, significantly increased risk of death was found in patients with nonsmall-cell lung cancer (OR: 2.37; 95% CI: 1.19-4.73; P=0.01) and colorectal cancer (OR: 2.84; 95% CI: 1.02-7.96; P=0.05).Among different VEGFR-TKIs, sorafenib and sunitinib had significant risk of death when compared with control arms, respectively.The present work pointed out a significantly increased risk of death due to VEGFR-TKIs.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.

ABSTRACT

Background: Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have widely been used in advanced cancer. However, these drugs may also lead to serious adverse events. The present meta-analysis aimed to determine the overall incidence and risk of deaths due to VEGFR-TKIs with more detailed subgroup analysis.

Materials and methods: PubMed, Web of Science, and Cochrane databases were searched for randomized controlled trials (RCTs) that compared VEGFR-TKIs with non-VEGFR-TKIs in the treatment of solid cancer. Pooled incidence, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included trials.

Results: A total of 14,139 participants from 41 RCTs were enrolled. The pooled incidence of death due to VEGFR-TKIs was 1.9% (95% CI: 1.6%-2.3%) with an OR of 1.85 (95% CI: 1.33-2.58; P<0.01) when compared with control groups. On subgroup analysis, significantly increased risk of death was found in patients with nonsmall-cell lung cancer (OR: 2.37; 95% CI: 1.19-4.73; P=0.01) and colorectal cancer (OR: 2.84; 95% CI: 1.02-7.96; P=0.05). Among different VEGFR-TKIs, sorafenib and sunitinib had significant risk of death when compared with control arms, respectively. VEGFR-TKIs in combination with other antineoplastic agents, but not VEGFR-TKI monotherapy, significantly increased the risk of treatment-related deaths. No heterogeneity was noted across all the prespecified subgroups regarding ORs.

Conclusion: The present work pointed out a significantly increased risk of death due to VEGFR-TKIs. Close monitoring should be emphasized in patients receiving these drugs.

No MeSH data available.


Related in: MedlinePlus