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Cabozantinib holds promise for bone metastases in HR-positive breast cancer

Key clinical point: More than a third of patients with hormone receptor (HR)-positive breast cancer and bone metastases showed a partial response to cabozantinib in a phase 2 trial.

Major finding: A total of 20 (38.5%) out of 52 patients had a partial response and 6 (11.5%) had a stable disease. The median overall survival was 19.6 months, and the median progression-free survival was 4.3 months.

Study details: The data come from a single-arm open-label phase 2 trial (n = 52) of cabozantinib with a starting dose of 100 mg, which was subsequently reduced to 60 mg/day for 12 weeks. The most frequent grade 3 or 4 toxicities were hypertension, anorexia, diarrhea, fatigue, and hypophosphatemia.

Disclosures: The trial was funded by Exelixis, Inc., and MJ Higgins was awarded the ASCO Career Development Award for the trial. MJ Higgins, SM Tolaney, MR Smith, M Fornier, U Mahmood, J Baselga, BA Chabner, and SJ Isakoff reported relationships with multiple pharmaceutical companies. J Xu, SE Come, and BY Yeap declared no conflicts of interest.


The combination of endocrine therapy plus a CDK 4/6 inhibitor is often first-line treatment for patients with metastatic hormone receptor (HR)-positive breast cancer. Development of endocrine resistance urges a need to identify promising targeted therapies for the later-line setting. This current trial investigated cabozantinib, a tyrosine kinase inhibitor that blocks multiple targets involved in cancer cell proliferation and metastatic potential. The relationship between bone-specific response and survival seen in this study is encouraging, and suggests there may be a subgroup of patients who derive greater clinical benefit from cabozantinib relative to another type of treatment. The toxicity profile of this agent differs from standard chemotherapy, and provider recognition is essential for early management. Furthermore, bone scan as a potential component of response evaluation is particularly intriguing, as measurable disease is a common inclusion criteria in clinical trials and capturing patients with bone-only involvement in this setting would be valuable.

Erin Roesch, MD

The Cleveland Clinic


Chandarlapaty S, Chen D, He W, et al. Prevalence of ESR1 Mutations in Cell-Free DNA and Outcomes in Metastatic Breast Cancer: A Secondary Analysis of the BOLERO-2 Clinical Trial. JAMA Oncol. 2016; 2:1310-1315.

Yakes FM, Chen J, Tan J, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011;


Costelloe CM, Chuang HH, Madewell JE, Ueno NT. Cancer Response Criteria and Bone Metastases: RECIST 1.1, MDA and PERCIST. J Cancer. 2010; 1:80-92.


Xu J et al. Oncologist. 2020 May 28. doi: 10.1634/theoncologist.2020-0127.