Format

Send to

Choose Destination
Ann Oncol. 2016 Jul;27(7):1304-11. doi: 10.1093/annonc/mdw160. Epub 2016 Apr 7.

Safety and clinical activity of vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitors after programmed cell death 1 inhibitor treatment in patients with metastatic clear cell renal cell carcinoma.

Author information

1
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore.
2
Department of Oncology, Levine Cancer Institute, Charlotte.
3
Fox Chase Cancer Center-Temple University Health System, Philadelphia.
4
Department of Oncology, Memorial Sloan Kettering Cancer Center, New York.
5
Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston.
6
Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, USA.
7
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore hhammer2@jhmi.edu.

Abstract

BACKGROUND:

Emerging agents blocking the programmed cell death 1 (PD-1) pathway show activity in metastatic clear cell renal cell carcinoma (mRCC). The aim of this study was to evaluate the efficacy and safety of vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-tyrosine kinase inhibitor (TKI) therapy after PD-1 inhibition.

PATIENTS AND METHODS:

Patients with mRCC treated with anti-PD-1 antibody (aPD-1) monotherapy or in combination (with VEGFR-TKI or ipilimumab) that subsequently received VEGFR-TKI were retrospectively reviewed. The efficacy end points were objective response rate (ORR) and progression-free survival (PFS) stratified by the type of prior PD-1 regimen. Safety by the type and PD-1 exposure was also evaluated.

RESULTS:

Seventy patients were included. Forty-nine patients received prior therapy with immune checkpoint inhibitors (CPIs) alone and 21 had combination therapy of aPD-1 and VEGFR-TKI. Overall, ORR to VEGFR-TKI after PD-1 inhibition was 28% (19/68) and the median PFS was 6.4 months (mo) (4.3-9.5). ORR to VEGFR-TKI after aPD-1 in combination with VEGFR-TKI was lower than that in patients treated with VEGFR-TKI after CPI alone (ORR 10% versus 36%, P = 0.039). In the multivariable analysis, patients treated with prior CPI alone were more likely to achieve an objective response than those treated with aPD-1 in combination with VEGFR-TKI (OR = 5.38; 95% CI 1.12-26.0, P = 0.03). There was a trend toward numerically longer median PFS in the VEGFR-TKI after the CPI alone group, 8.4 mo (3.2-12.4) compared with 5.5 mo (2.9-8.3) for those who had VEGFR-TKI after aPD-1 in combination with VEGFR-TKI (P = 0.15). The most common adverse events (AEs) were asthenia, hypertension, and diarrhea.

CONCLUSIONS:

The efficacy and safety of VEGFR-TKIs after PD-1 inhibition were demonstrated in this retrospective study. The response rate was lower and the median progression-free survival was shorter in those patients who received prior PD-1 in combination with VEGFR-TKI. PD-1 exposure does not seem to significantly influence the safety of subsequent VEGFR-TKI treatment.

KEYWORDS:

PD-1 inhibitor; ipilimumab; nivolumab; renal cell carcinoma; vascular endothelial growth factor receptor–tyrosine kinase inhibitor

PMID:
27059553
PMCID:
PMC6276905
DOI:
10.1093/annonc/mdw160
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center