CHICAGO—Bone metastases (BM) predict shorter progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) treated with molecularly targeted agents, according to new findings presented at the 2013 American Society of Clinical Oncology annual meeting. 

The findings are based on a pooled analysis of data from 2,749 patients with mRCC treated from 2003-2011. “We did this study because the treatment paradigm for metastatic renal cell carcinoma has changed significantly over the past decade and prognostic factors need to reflect changes in systemic therapy,” said investigator Rana McKay, MD, of the Dana-Farber Cancer Institute in Boston.

This is the largest study to date to analyzed BM in mRCC patients treated with molecularly targeted agents, Dr. McKay said. The investigators identified 1,059 treated with sunitinib, 335 treated with sorafenib, 359 treated with axitinib, 208 treated with temsirolimus, 208 treated with temsirolimus plus interferon-alfa, and 560 treated with interferon-alfa alone. Most patients were male (71%) and had a baseline ECOG performance status of 0 (47%) or 1 (51%). Of 2,749 patients, 91% had clear cell histology and 84% had undergone prior nephrectomy.

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A total of 285 patients (10.4%) received bisphosphonate therapy. Of these, 233 received zoledronic acid; no patient received denosumab. Among patients with BM, the SRE rate was 20.7% in patients receiving bisphosphonate therapy compared to 79.3% in patients not receiving bisphosphonate therapy, but the difference was not statistically significant.

She and her team found that bisphosphonate therapy was associated with an increased rate of osteonecrosis of the jaw, with six cases (2.1%) occurring in bisphosphonate recipients compared with only one case (less than 0.1%) in those not treated with a bisphosphonate. Bisphosphonate therapy was also associated with hypocalcemia (7.4% vs. 3.0%) and renal insufficiency (4.9% vs. 2.5%).

The presence of baseline BM (compared with its absence) was associated with a statistically significant shorter PFS (5.1 vs. 6.7 months) and shorter OS (13.2 vs. 20.2 months). Dr. McKay said the use of bisphosphonate therapy was not associated with improved PFS or OS compared with patients not receiving bisphosphonate therapy.

In addition to providing prognostic information, data regarding site of metastases may have therapeutic implications and inform the use of newer agents currently under investigation in mRCC. Larger prospective studies are needed to better define the efficacy and toxicity of concomitant bisphosphonates and molecularly targeted therapy in mRCC, which will be instrumental in guiding future clinical practice.