Bone Metastases Result in Worse Outcomes for RCC Patients

Bone metastases result in poorer outcomes for those patients with advanced renal cell carcinoma (RCC) who were treated with a molecularly targeted therapy. The results were presented in two separate analyses at the annual meeting of the American Society of Clinical Oncology (ASCO).

One of the studies analyzed whether bone or liver metastasis affected outcomes for patients being treated with molecularly targeted agents. An international group of researchers reviewed RCC data from 2,027 patients who are part of the International Metastatic Renal-Cell Carcinoma Database Consortium. All patients were treated between 2003 and 2012. Bone and liver metastasis both independently predicted poorer survival compared with patients with metastasis to other sites.

Those patients with a single metastatic site, either at the bone or in the liver, had a worse overall survival compared with patients with metastases at other sites (lung, lymph node, adrenal, soft tissue, and brain). The median overall survival for a single metastatic site, excluding the liver or bone, was 32.9 months compared with 16.8 months for patients with a single bone metastasis and 16.4 months for patients with a single liver metastasis (P = .032).

The trend was similar for patients with two or more metastases: Those patients with bone and liver metastases had a shorter time to treatment failure (4.2 months vs 7.3 months; P < .0001). Overall survival was also significantly lower for patients with liver and bone metastases.

A vast majority of patients included in the analysis were treated with a VEGF-targeted agent as a first-line therapy (1,978 patients), while 49 patients were treated with an mTOR inhibitor as a first-line treatment.

Another study showed that the presence of bone metastases is an adverse risk for both shorter progression-free and overall survival. Rana R. McKay, MD, of the Dana-Farber Cancer Institute, and colleagues pooled 2,749 RCC patient data from eight phase II and phase III trials. Patients were treated with sunitinib, sorafenib, axitinib, temsirolimus, or interferon alfa. Thirty-two percent (781 patients) of the patients had bone metastases.

Bone metastasis was linked to a 1.6-month shorter progression-free survival compared with patients who did not have bone metastases (5.1 months vs 6.7 months, respectively; P < .0008). Overall survival was also shorter for patients harboring bone metastases (13.2 months vs 20.2 months; P < .0001) compared with those without bone metastases. The use of bisphosphonate therapy (mostly zoledronic acid) in patients with metastasis of the bone did not improve either progression-free survival or overall survival. No patient in the pooled cohort received denosumab.

The treatment paradigm for RCC has rapidly evolved as new targeted therapies have been approved. However, the effect of these agents on patients with different types of metastatic disease has not been extensively analyzed. Future studies need to better define both the efficacy and the associated toxicities of these molecular agents when combined with bisphosphonates.