Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Genitourinary tumours, non-prostate

2307 - Pazopanib (P) or Sorafenib (S) + Radium-223 (Rad) in Metastatic Renal Cell Carcinoma (mRCC) with Bone Metastases (BM)

Date

10 Sep 2017

Session

Genitourinary tumours, non-prostate

Topics

Cytotoxic Therapy;  Renal Cell Cancer

Presenters

Dominick Bossé

Citation

Annals of Oncology (2017) 28 (suppl_5): v295-v329. 10.1093/annonc/mdx371

Authors

D. Bossé1, R.R. McKay2, K.P. Gray3, M.D. Michaelson4, C. Sleeper1, M. Walsh1, K.M. Krajewski5, H. Jacene6, J. Bellmunt1, M.M. Pomerantz1, L.C. Harshman1, T.K. Choueiri1

Author affiliations

  • 1 Lank Center For Genitourinary Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 2 Medical Oncology, Moores Cancer Center in San Diego, San Diego/US
  • 3 Biostatistics And Computational Biology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 4 Genitourinary Cancer Center, Massachusetts General Hospital Cancer Center, Boston/US
  • 5 Radiology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 6 Nuclear Medicine, Dana-Farber Cancer Institute, 02215 - Boston/US
More

Resources

Abstract 2307

Background

BM occur in 30% of patients (pts) with mRCC and are associated with symptomatic skeletal events (SSE) and worse outcomes with vascular-endothelial growth factor (VEGF)-targeted agents. Rad is a bone-seeking α-emitter that targets BM. We investigated the safety, efficacy and bone turnover markers (BTM) of Rad combined with P or S in pts with mRCC and BM.

Methods

30 pts received therapy (15 treatment-naïve pts: P 800 mg/d +Rad; 15 treatment-refractory: S 400 mg BID +Rad). Rad was administered monthly for up to 6 infusions. The primary endpoint was BTM. Secondary endpoints included safety, SSE rate, time to SSE, objective response rate (ORR), narcotic use and survival.

Results

Of the 30 pts, 70% had clear cell histology, 17% were IMDC poor risk and 33% had liver metastases. Prior SSEs were reported in 100% and 65% of pts in the P and S cohorts, respectively. 1 pt had received denosumab. Median changes in BTM at cycle 2 and 4 compared to baseline are summarized in table and show declines in all BTMs. Best ORR by RECIST was partial response (PR) in 13% and stable disease (SD) 47%. Achieving > =50% decline in PINP at cycle 2 was associated with PR and SD (Fisher’s exact p-value 0.01). Median treatment duration was 3.6 mo (IQR 1.5, 5.5). Progression-free survival was 8.2 mo [95%CI 5.6, NR] and 4.6 mo [95%CI 2.1, NR] in pts treated with P and S. Overall survival was 11.9 mo [95%CI 7.8, NR] and 8.7 mo [95%CI 6, NR], respectively. Overall rate of SSE on study was 47%; 67% in the P cohort (median time to SSE 6.3 mo [95%CI 3.6, NR]) and 27% in the S cohort (median time to SSE NR [95%CI 6.6 mo, NR]). There was no dose-limiting toxicity. The rate of treatment-related grade ≥3 toxicity was 39.3% including 3.6% grade 3 anemia.

Conclusions

Rad combined with P or S is safe and well tolerated. All BTMs significantly declined with Rad combined with P or S suggesting biologic activity in mRCC with BM. Randomized trials are needed to evaluate the role of Rad on SSE prevention in these pts.Table:

854PD

BTMBaseline (IQR) N = 30% change at cycle 2 median (IQR) N = 21% change at cycle 4 median (IQR) N = 18
Bone-specific alkaline phosphatase (BALP)11 (9, 16) ug/mL−17 (-36, -7)−23 (-32, -7)
Osteocalcin (OC)16 (12, 19) ng/mL−33 (-45, -21−49 (-52, -31)
N-terminal propeptide of procollagen type I (PINP)46 (30, 66) ug/mL−57 (-63, -29)−63 (-69, -44)
C-terminal cross-linked telopeptide of type I collagen (CTX)432 (210, 595) pg/mL−37 (-51, -1)−34 (-49, -22)
N-terminal cross-linked telopeptide of type I collagen (NTX)15 (11,21) nM BCE−28 (-43, -7)−28 (-43, -15)

Clinical trial identification

Clinical trial information NCT02406521

Legal entity responsible for the study

Dana-Farber Cancer Institute

Funding

Bayer

Disclosure

R.R. McKay: Research funding from Bayer and Pfizer. M.D. Michaelson: Advisory honoraria received from Novartis, Exelixis and Pfizer. H. Jacene: Research funding GTx, Inc, Seimens Healthcare. J. Bellmunt: Reports research support from Novartis and Sanofi; consulting support from OncoGenex, AstraZeneca, Merck, Bristol Myers-Squibb, Genentech, Inovio, Champions Oncology, Seattle Genetics and Pierre Fabre. L.C. Harshman: Advisory board of Genentech, Pfizer, Dendreon, NCCN, Medivation, Kew and has received research funding/support from Bayer, Medivation/Astellas, Pfizer, Dendreon, Sotio, Genentech, Merck, Bristol-Myers Squib, Jannsen. T.K. Choueiri: Received institutional research funding from Pfizer, exelixis, Bristol-Myers Squib, Novartis, and has an advisory role at Pfizer, Novartis, Genentech, Merck, Bristol-Myers Squib and Bayer. The remaining authors have no disclosures. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.