ESMO 2017: Pazopanib or Sorafenib + Radium-223 in Metastatic Renal Cell Carcinoma with Bone Metastases

Madrid, Spain ( Bone metastases occur in 30% of patients with metastatic renal cell carcinoma (mRCC) and are associated with symptomatic skeletal events (SREs), as well as worse outcomes with vascular-endothelial growth factor (VEGF)-targeted agents. At today’s poster discussion session at ESMO 2017, Dr. Bosse and colleagues presented initial findings of their study assessing pazopanib or sorafenib + radium-223 in patients with mRCC and bone metastases. Since radium-223 is a bone-seeking α-emitter that targets bone metastases, the objective of the study was to investigate the safety, efficacy and bone turnover markers of radium-223 combined with either pazopanib or sorafenib.

For this trial, 30 patients received treatment: treatment-naïve patients received pazopanib 800 mg/d + radium-223 (n=15) and treatment-refractory patients received sorafenib 400 mg BID + radium-223 (n=15). Radium-223 was administered monthly for up to six infusions. The primary endpoint was bone turnover markers (bone-specific alkaline phosphatase, osteocalcin, N-terminal propeptide of procollagen type I (PINP), C-terminal cross-linked telopeptide of type I collagen, and N-terminal cross-lined telopeptide of type I collagen) and secondary endpoints included safety, SRE rate, time to SRE, objective response rate (ORR), narcotic use and survival. Among these 30 patients, 70% had clear cell histology, 17% were IMDC poor risk and 33% had liver metastases. Prior SREs were reported in 100% and 65% of patients in the pazopanib and sorafenib cohorts, respectively. Median changes for all bone turnover markers showed a decline at cycle 2 and 4 compared to baseline. The best ORR by RECIST was partial response in 13% of patients and stable disease in 47%. Achieving a ≥50% decline in PINP at cycle 2 was associated with partial response and stable disease (Fisher’s exact p-value 0.01). The median treatment duration was 3.6 months (IQR 1.5, 5.5), and progression-free survival was 8.2 months [95%CI 5.6-NR] and 4.6 months [95%CI 2.1-NR] in patients treated with pazopanib and sorafenib, respectively. Overall survival was 11.9 months [95%CI 7.8-NR] for patients treated with pazopanib and 8.7 months [95%CI 6-NR] for those treated with sorafenib. Overall rate of SREs on study was 47%, including 67% in the pazopanib cohort (median time to SRE 6.3 months [95%CI 3.6-NR]) and 27% in the sorafenib cohort (median time to SRE NR [95%CI 6.6-NR]). There was no dose-limiting toxicity and the overall rate of treatment-related grade ≥3 toxicity was 39.3%.

In this phase I trial, radium-223 combined with pazopanib or sorafenib was safe and well-tolerated. All five bone turnover markers significantly declined with radium-223 combined with pazopanib or sorafenib, suggesting biologic activity in mRCC with bone metastases. As the authors note, further trials are required to assess the role of radium-223 on SRE prevention in these patients.

Speaker: Dominick Bossé, Dana Farber Cancer Institute, Boston, United States of America

Co-Authors: R. R. McKay (San Diego, United States of America) K. P. Gray (Boston, United States of America) M. D. Michaelson (Boston, United States of America) C. Sleeper (Boston, United States of America) M. Walsh (Boston, United States of America) K. M. Krajewski (Boston, United States of America) H. Jacene (Boston, United States of America) J. Bellmunt (Boston, United States of America) M. M. Pomerantz (Boston, United States of America)
L. C. Harshman (Boston, United States of America) T. K. Choueiri (Boston, 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