Skip to main content
Latest news
Browse specialties
Breast cancer Genitourinary cancers Lung & thoracic cancers
In focus
Next-generation sequencing: Emerging biomarkers in thyroid and NSCLCs ctDNA and bladder cancer: Current understanding and beyond ROS1 fusion-positive NSCLC NSCLC driver mutations: Discussing the importance of RET, ALK and ROS1 alterations in NSCLC Early-stage NSCLC management: Surgery, targeted treatment and immunotherapy ALK fusion-positive NSCLC: International approaches to management RET fusion-positive NSCLC: Informing on the use of pralsetinib for patients with RET fusion-positive, advanced NSCLC COVID-19 & cancer
Conferences
SABCS 2022 ESMO 2022 2022 ASCO Annual Meeting
About us
Medicine Matters Oncology
EXTENDED SEARCH
Top

23-05-2018 | Renal cell carcinoma | Article

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

Journal: British Journal of Cancer

Authors: Pedro Coelho Barata, Alfonso Gomez De Liano, Prateek Mendiratta, Valerie Crolley, Bernadett Szabados, Laura Morrison, Laura Wood, Kimberly Allman, Allison Tyler, Allison Martin, Timothy Gilligan, Petros Grivas, Moshe Ornstein, Jorge A. Garcia, Thomas Powles, Brian I. Rini

Publisher: Nature Publishing Group UK

Login to get access

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.
Literature
1.
Motzer, R. J. et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N. Engl. J. Med. 369, 722–731 (2013).CrossRef
2.
Motzer, R. J. et al. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 14, 552–562 (2013).CrossRef
3.
Motzer, R. J. et al. Sunitinib versus Interferon Alfa in metastatic renal-cell carcinoma. N. Engl. J. Med. 356, 115–124 (2007).CrossRef
4.
Rini, B. I. et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J. Clin. Oncol. 26, 5422–5428 (2008).CrossRef
5.
Motzer, R. J. et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372, 449–456 (2008).CrossRef
6.
Motzer, R. J. et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N. Engl. J. Med. 373, 1803–1813 (2015).CrossRef
7.
Oyama, T. et al. Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-κB activation in hemopoietic progenitor cells. J. Immunol. 160, 1224–1232 (1998).
8.
Ko, J. S. et al. Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin. Cancer Res. 15, 2148–2157 (2009).CrossRef
9.
Atkins, M. B. et al. Phase Ib dose-finding study of axitinib plus pembrolizumab in treatment-naïve patients with advanced renal cell carcinoma. J. Immunother. Cancer 3(S2), P353 (2015).CrossRef
10.
Amin, A. et al. Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with sunitinib or pazopanib in patients (pts) with metastatic renal cell carcinoma (mRCC). J. Clin. Oncol. 32(15_suppl), 5010–5010 (2014).CrossRef
11.
Sznol, M. et al. Phase Ib evaluation of MPDL3280A (anti-PDL1) in combination with bevacizumab (bev) in patients (pts) with metastatic renal cell carcinoma (mRCC). J. Clin. Oncol. 33(7_suppl), 410–410 (2015).CrossRef
12.
Motzer RJ, Tannir NM, McDermott DF et al (2018) Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. New England Journal of Medicine 378(14), 1277–1290.CrossRef
13.
Heng, D. Y. et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J. Clin. Oncol. 27, 5794–5799 (2009).CrossRef
14.
Eisenhauer, E. A. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer 45, 228–247 (2009).CrossRef
15.
US Department of Health. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. National Cancer Institute. 2009.
16.
Rini, B. I. et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 378, 1931–1939 (2011).CrossRef
17.
Choueiri, T. K. et al. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N. Engl. J. Med. 373, 1814–1823 (2015).CrossRef
18.
Arranz Arija, J. et al. 884PSPAZO2 (SOGUG): Comparative effectiveness of pazopanib in metastatic renal carcinoma (mRC): Ineligible (I) vs eligible (E) patients for clinical trials. Ann. Oncol. 28(suppl_5), (2017).
19.
Wells, J. C. et al. Third-line targeted therapy in metastatic renal cell carcinoma: results from the international metastatic renal cell carcinoma database consortium. Eur. Urol. 71(2), 204–209 (2017).CrossRef
  • » This content is intended only for healthcare providers and was made possible by educational funding provided by F. Hoffmann-La Roche Ltd.
Image Credits