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.

Fig. 1

Algorithm of first-line and second-line therapies

Fig. 2

Best response to second-line targeted therapy grouped by initial best response to first-line targeted therapy. Abbreviations: CR1 complete response to first-line VEGF-targeted therapy, PR1 partial response to first-line VEGF-targeted therapy, SD1 stable disease to first-line VEGF-targeted therapy, PD1 progressive disease to first-line VEGF-targeted therapy, CR2 complete response to second-line VEGF-targeted therapy, PR2 partial response to second-line VEGF-targeted therapy, SD2 stable disease to second-line VEGF-targeted therapy, PD2 progressive disease to second-line VEGF-targeted therapy

Fig. 3

First-line PFS of VEGF-targeted therapy in patients who eventually receive second-line VEGF-targeted therapy

Fig. 4

Second-line PFS of VEGF-targeted therapy in patients who eventually receive second-line VEGF-targeted therapy

Fig. 5

Correlation between progression-free survival on first-line VEGF-targeted therapy and progression-free survival on second-line VEGF-targeted therapy