The efficacy of VEGFR TKI therapy after progression on immune combination therapy in metastatic renal cell carcinoma

Br J Cancer. 2018 Jul;119(2):160-163. doi: 10.1038/s41416-018-0104-z. Epub 2018 May 24.

Abstract

Background: The outcome of patients who progress on front-line immune-based combination regimens (IC) including immune checkpoint inhibitors (CPI) and receive subsequent systemic therapy is unknown.

Methods: Retrospective analysis of consecutive patients with clear-cell mRCC who progressed on one of seven clinical trials investigating an IC and received ≥1 line of subsequent VEGFR TKI therapy.

Results: Thirty-three patients [median age 57 (37-77), 85% male, 73% ECOG 0] were included. For evaluable patients (N = 28), the best response to first subsequent therapy was 29% partial response, 54% stable disease, and 18% progressive disease. The median PFS (mPFS) for first subsequent therapy was 6.4 months (95% CI, 4.4-8.4); no difference in mPFS by prior type of IC (VEGFR TKI-CPI vs. CPI-CPI) was noted (p = 0.310). Significant AEs were observed in 30% of patients, more frequently transaminitis (9%).

Conclusions: VEGFR TKIs have clinical activity in mRCC refractory to IC therapy, possibly impacted by the mechanism of prior combination therapy.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / pathology
  • Combined Modality Therapy
  • Disease Progression
  • Disease-Free Survival
  • Everolimus / administration & dosage
  • Female
  • Humans
  • Immunotherapy*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Protein Kinase Inhibitors / administration & dosage*
  • Sirolimus / administration & dosage
  • Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-1 / genetics*

Substances

  • Protein Kinase Inhibitors
  • Everolimus
  • Vascular Endothelial Growth Factor Receptor-1
  • Sirolimus