Table 1.
Evidence for development of hypertension as a prognostic indicator of cancer outcome during VEGF receptor inhibitor treatment
| Year | Agent studied | Type of study | N | Patients with VEGFi hypertension | Patients without VEGFi hypertension |
p-value | Ref |
|---|---|---|---|---|---|---|---|
| 2007 | Sunitinib | Retrospective | 40 | 66% disease response | 26% disease response | 0.009 | [66] |
| 2009 | Bevacizumab | Retrospective | 39 | Median PFS 14.5 months | Median PFS 3.1 Months | 0.04 | [67] |
| 2010 | Bevacizumab | RCT | 878 | Median OS 15.9 months | Median OS 11.5 Months | < 0.0001 | [68] |
| 2011 | Bevacizumab | Prospective | 101 | Median OS 25.8 months | Median OS 11.7 Months | < 0.0001 | [69] |
| 2012 | Sunitinib | Retrospective | 319 | Median OS 19.8 months | Median OS 14.5 months | 0.0003 | [70] |
| 2013 | Bevacizumab | Retrospective | 6486 | Early rise in BP > 10 or > 20 mmHG systolic only predicted benefit in 1/7 clinical trials analyzed | varied | [71] | |
| 2013 | Bevacizumab | Retrospective | 60 | Trend towards higher median OS for patients with grade 3 HTN compared to grades 0–2, but not significant | 0.058 | [72] | |
| 2014 | Bevacizumab | Retrospective | 82 | Median OS 11.7 months | Median OS 4.9 months | < 0.001 | [79] |
| 2015 | Multiple | Retrospective | 1120 | HR for OS, 0.76 (95% CI, 0.65–0.89) for HTN compared to no HTN | 0.0004 | [78] | |
| 2018 | Bevacizumab | Meta-analysis | 2292 | HR for OS 0.51 (95% CI: 0.39–0.65) for HTN compared to no HTN | < 0.001 | [74] | |
| 2019 | Apatinib | Retrospective | 110 | Median OS 9.9 months | Median OS 7.8 months | 0.005 | [65] |
| 2019 | Aflibercept | Retrospective | 78 | Median OS 10.6 months | Median OS 4.0 months | < 0.001 | [75] |
| 2019 | Multiple TKIs | Meta-analysis | 4661 | HR for PFS 0.56 (95% CI: 0.40–0.77) for studies 2011–2014, 0.61 (95% CI: 0.48–0.77) for 2015–2017 | < 0.001 for both | [77] | |
| 2021 | Alontinib | Post hoc | 109 | HR for OS 0.74 (95% CI: 0.31–1.77) in patients with preexisting HTN and 0.37 (95% CI: 0.21–0.67) in patients without preexisting HTN | Not given | [64] | |
| 2021 | Bevacizumab | Retrospective | 117 | Median OS 7.7 months | Median OS 4.4 months | 0.011 | [76]* |
| 2021 | Multiple TKIs | Retrospective | 38 | Median OS 8.6 months | Median OS 3.6 months | 0.03 | [76]* |
Studies in patients treated with VEGF inhibitors comparing outcomes in patients who developed hypertension versus those who did not. VEGFRi VEGF receptor inhibitor, PFS progression free survival, OS overall survival, HR hazard ratio, BP blood pressure, HTN hypertension, and 95% CI 95% confidence interval. All differences in PFS or OS were statistically significant unless mentioned in the table.
*
Subgroup analyses from a single study