Abstract CT129: Phase 2 study of cabozantinib in patients with non-breast, non-prostate cancer with bone metastasis
Authors: Choy Edwin , Cote Gregory M. , Michaelson M. Dror , Wirth Lori , Gainor Justin F. , Sequist Lecia V. , Sullivan Ryan J. , Fidias Panagiotis M. , Shaw Alice , Heist Rebecca S. 
Published: July 2017

Abstract
IntroductionWe sought to test the safety and efficacy of cabozantinib in patients with advanced solid (non-breast, non-prostate) malignancies and bony metastasis (ClinicalTrials.gov Identifier: NCT01588821). Patients with bone metastasis were enrolled in this study. Primary endpoint of the study was change in bone biomarkers in serum and urine. Tumor responses were an additional endpoint and measured by RECIST v1.1.
Methods:Participants with progressive metastatic solid tumors other than breast and prostate cancer, age &gt;/= 18 yrs, and with bone metastasis were consented and enrolled onto open label phase II study at Massachusetts General Hospital. The starting dose was 60 mg/d cabozantinib. CT of the tumor, chest, abdomen, and pelvis were performed every 2 cycles (each cycle = 28 days). Serial PET and Tc99m bone scans were performed in a subset of participants. Radiologic tumor responses were evaluated by RECIST. Bone biomarkers were measured at baseline and week 8, with a bony response to treatment defined as ≥ 40% decrease in urinary Ntx, serum Ntx, or serum Ctx at week 8.
Results:37 patients enrolled onto this study. 14 had sarcoma, 7 renal cell carcinoma, 5 non-small cell lung cancer, 4 head and neck carcinoma, 2 thyroid cancer, 2 melanoma, 1 adenoid cystic carcinoma, 1 metastatic chondroblastoma, and 1 chordoma. Patient age at enrollment ranged from 18 to 83 years, with an average age of 54.4 years old. 37 % of patients were female. 19 patients were evaluable for determination of response by bone biomarkers. 13 had ≥ 40% decrease in serum Ctx, 9 had ≥ 40% decrease in serum Ntx, and 8 had ≥ 40% decrease in urinary Ntx. These measurements, however, had low correlation with RECIST measurements (r^2 of .05, .00, and .15, respectively).The average time to disease progression was 6.6 months. 3 patients had a partial response by RECIST (with chondroblastoma, head and neck cancer, and thyroid cancer), 16 of 20 radiologically measureable patients had some decrease in tumor size as best response, and 9 of those 16 had decrease in tumor size by 10% or greater by RECIST, and 6 of those 9 had sarcoma or chondroblastoma. The other 17 of 37 enrolled patients had bone only disease or were otherwise not measureable by RECIST. 55% of patients required dose reduction. Most common all grade adverse events were fatigue (59%), nausea (46%), anorexia (32%), and plantar-palmar erythrodysesthesia (27%).
Conclusion:Cabozantinib is an active drug for patients with bone metastasis as measured by changes in serum/urine Ntx and Ctx. Plantar-palmar erythrodysesthesias, fatigue, nausea, and anorexia were common adverse events. Adverse events were manageable by dose reduction to 40 mg QD. This is the first study showing that cabozantinib has significant anti-tumor activity in patients with metastatic sarcoma with bone metastasis.
Citation Format: Edwin Choy, Gregory M. Cote, M. Dror Michaelson, Lori Wirth, Justin F. Gainor, Lecia V. Sequist, Ryan J. Sullivan, Panagiotis M. Fidias, Alice Shaw, Rebecca S. Heist. Phase 2 study of cabozantinib in patients with non-breast, non-prostate cancer with bone metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT129. doi:10.1158/1538-7445.AM2017-CT129