ESMO 2017: Outcomes of patients with metastatic renal cell carcinoma who were treated with second-line vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) after first-line immune checkpoint inhibitor therapy

Madrid, Spain (UroToday.com) Dr. Shah and colleagues from the MD Anderson Cancer Center presented their results of metastatic renal cell carcinoma (mRCC) patients receiving VEGFR-TKI therapy after first-line immune checkpoint inhibitor therapy at today’s poster session at ESMO 2017. Immune checkpoint inhibitor therapy is an established strategy in mRCC after progressive disease on VEGFR-TKI, however little data exists in the reverse sequence on response rate, progression-free survival (PFS), safety, and tolerability of TKI after first-line immune checkpoint inhibitor therapy.

For this study, a retrospective analysis of patients with mRCC treated from 2015 to present with first-line immune checkpoint inhibitor therapy, followed by second-line TKI was performed. Response assessment was provided by a blinded radiologist using RECIST 1.1. Descriptive statistics, Fisher’s test and Wilcoxon rank sum test were used. There were 27 clear-cell mRCC patients with follow-up of at least 8 weeks on TKI post first-line immune checkpoint inhibitor therapy. Median age at diagnosis was 58 years, 78% of patients had lung, 37% bone, 37% lymph node, and 7% liver metastasis. As first-line therapy, 7 patients received nivolumab, 17 received nivolumab + ipilimumab, and 3 received nivolumab + bevacizumab. All 27 patients had resolution of Grade 3/4 toxicities from immune checkpoint inhibitor therapy and progressive disease at the time of TKI initiation. Median time from discontinuation of immune checkpoint inhibitor therapy to initiation of TKI was 4.1 weeks (range 0-23.3 weeks). There were 11 patients (41%) who had a partial response (8 of whom had ≥40% tumor reduction), and 16 (59%) patients who had stable disease as best response to TKI. The median PFS was 10.0 months (95%CI 6.8-NR). Nine patients discontinued second-line TKI after a median of 26.3 weeks (range 4.6-44 weeks), 8 patients because of disease progression and one because of toxicity. Two patients developed Grade 3 transaminitis and three patients had Grade 3 hand-foot skin reaction. Age, sex, IMDC risk score, nephrectomy status, and TKI agent did not predict partial response or stable disease.

In summary, this small retrospective study observed a high response rate (41%), median PFS 10 months, and manageable toxicity in patients with mRCC treated with TKI after immune checkpoint inhibitor therapy. Further studies are needed to evaluate the optimal sequencing of therapies in clear cell mRCC, as it remains to be seen whether combination of immunotherapy or immunotherapy + TKI will prove to be superior to sequential immunotherapy followed by TKI or TKI followed by immunotherapy.

Speaker: Amishi Y. Shah, University of Texas, MD Anderson Cancer Center, Houston, United States of America

Co-Authors: E. A. Lemke (Houston, United States of America) G. Jianjun (Houston, United States of America) A. Chandamohan (Houston, United States of America) M. T. Campbell (Houston, United States of America) A. Zurita Saavedra (Houston, United States of America) L. Xiao (Houston, United States of America) J. Wang (Houston, United States of America) P. G. Corn (Houston, United States of America) E. Jonasch (Houston, United States of America) P. Sharma (Houston, United States of America) N. Tannir (Houston, United States of America)

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain

References:

Prinsloo S, Wei Q, Scott SM, et al. Psychological states, serum markers and survival: Associations of predictors of survival in patients with renal cell carcinoma. J Behav Med 2015;38(1):48-56.
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