Published: May 29, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.

Action Points

CHICAGO -- For patients with metastatic renal cell carcinoma, prognostic factors at baseline appear to distinguish those who will be long-term survivors after targeted therapy, researchers are reporting.

While targeted therapies have improved outcomes, not all patients do well, and those at either end of the survival curve need to be characterized, according to Wanling Xie, PhD, of Dana-Farber Cancer Institute in Boston, and colleagues in the International Metastatic Renal Cell Carcinoma Database Consortium.

To clarify the distinctions, Xie and colleagues analyzed retrospective information on more than 2,100 patients treated from 2004 through 2007, and will be reporting on it here at the annual meeting of the American Society of Clinical Oncology.

Kidney cancers -- most of them renal cell carcinomas -- are about 2% of all adult malignancies and account for about 208,000 new diagnoses and 102,000 deaths around the world every year.

The introduction of targeted therapies radically changed the treatment of metastatic renal cell carcinoma. New drugs have aimed at two targets in particular -- signaling of vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR).

Approved drugs targeting VEGF include the monoclonal antibody bevacizumab (Avastin) and the receptor tyrosine kinase inhibitors sunitinib (Sutent), sorafenib (Nexavar), and pazopanib (Votrient).

The mTOR inhibitors temsirolimus (Torisel) and everolimus (Afinitor) are also approved.

But it has not been completely clear which patients will do well with the targeted therapies and which will not, so Xie and colleagues looked at a host of factors in 2,161 patients.

Of those, they are reporting, 152 patients who survived 4 or more years after starting targeted therapy were designated as long-term survivors. Median survival in the group was 69.3 months.

They were compared with 218 patients who survived no more than 6 months -- the short-term survivors, with a median survival after starting targeted therapy of 3.1 months.

The bottom line, Xie and colleagues found, was that partial response or better to the targeted therapy predicted the chance of becoming a long-term survivor.

In a multivariate analysis, adjusting for all the prognostic factors, those who responded to the therapy had an odds ratio for long-term survival of 6.3 (95% CI 2.3 to 17.4, P=0.0004).

All told, 38% of those who had a complete or partial response went on to be long-term survivors, compared with 4% of those who were short-term survivors.

Xie and colleagues are also reporting that long-term survivors were significantly less likely (at P<0.0001 for all) to have:

• A Karnofsky performance status of less than 80%, at 7% versus 53%
• Less than a year between diagnosis and treatment
• Hypercalcemia, anemia, thrombocytosis and neutrophilia

Among long-term survivors, 73% had more than one metastatic site, compared with 83% of the short-term survivors (P<0.02).

On the other hand, long-term survivors were significantly more likely (P<0.0001) to have a prior nephrectomy – at 95% versus 65%.

When patients were stratified by the 2009 prognostic categories of Heng et al, 42% of long-term survivors had a favorable prognosis compared with just 2% of those in the short-term group.

Of those in the poor category, 3% went on to be long-term survivors and 60% lived no more than 6 months, Xie and colleagues are reporting.

Finally, they found, long-term survivors had longer treatment duration than short-term survivors (23.6 months versus 2.0) and more use of second-line targeted therapy (11.5 months versus 0.8).

The researchers did not report external support for the consortium. Xie said he had no conflicts.

Primary source:Journal of Clinical Oncology
Source reference:
Xie W, et al "Characteristics of long-term and short-term survivors of metastatic renal cell carcinoma (mRCC) treated with targeted therapy: Results from the International mRCC Database Consortium" J Clin Oncol 2012; 30(suppl): Abstract 4538.

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Michael Smith

North American Correspondent

North American Correspondent for MedPage Today, is a three-time winner of the Science and Society Journalism Award of the Canadian Science Writers’ Association. After working for newspapers in several parts of Canada, he was the science writer for the Toronto Star before becoming a freelancer in 1994. His byline has appeared in New Scientist, Science, the Globe and Mail, United Press International, Toronto Life, Canadian Business, the Toronto Star, Marketing Computers, and many others. He is based in Toronto, and when not transforming dense science into compelling prose he can usually be found sailing.

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