Although the efficacy of targeted therapy for metastatic renal cell cancer is well established when prior nephrectomy is performed, research reports on the effectiveness of targeted therapy for treatment of the primary tumor have largely been anecdotal. Some case reports, however, have shown a dramatic response when targeted therapy is used prior to nephrectomy in bulky primary tumors. Yet the largest study to date of targeted therapy in metastatic renal cell cancer shows that such dramatic responses occur very rarely, according to research presented at the 2010 Genitourinary Cancers Symposium in San Francisco.¹

Low Partial Response Rate

In the study of 143 patients with metastatic renal cell cancer, only 5.6% had a primary tumor partial response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) after a median follow-up of 1 year. However, 35% of patients experienced 11% to 30% shrinkage of their tumor, and only 7% experienced an increase in tumor size of greater than 11%.

"Patients with big complex tumors who do not undergo an upfront cytoreductive nephrectomy may have a meaningful response in the primary tumor, but it's unlikely to be a dramatic response," said lead researcher E. ­Jason Abel, MD, a Clinical Fellow in Urologic Oncology at The University of Texas M. D. Anderson Cancer Center. "It's important to be realistic about your expectations," he added.

Dr. Abel noted that in the study, patients who did best on targeted therapy experienced an early response-within the first 90 days. Those who had a greater than 10% response within the first 90 days, or about one-third of patients, had a maximum response of 24%. By contrast, patients without an early response, or about two-thirds of patients, had a maximum response of only 10%, Dr. Abel said. "If you don't get more than a 10% response in the first 90 days, the chances decrease for having a dramatic response," Dr. Abel said.

Sunitinib Produced Best Response

In the study, patients were treated with a wide variety of targeted therapy agents. Those treated with sunitinib (Sutent) had the best overall response when compared to therapy with other agents-3 patients on sunitinib experienced a partial response, and 21 showed a 10% to 30% decrease in the size of their tumors. Dr. Abel noted that if newer-generation targeted therapies were more active in primary tumors, it would be more promising for presurgical therapy. Patients who would benefit most from presurgical therapy would be those who have large tumors, tumors that are invasive into other organs, or a large volume of metastatic disease, he added.

"The use of targeted therapies in metastatic renal cell cancer as a means to shrink the tumor is a hot topic today," commented Nicholas Vogelzang, MD, Chair and Medical Director of the Developmental Therapeutics Committee of US Oncology, and Vice Chair of the genitourinary committee of the Southwest Oncology Group. Dr. Vogelzang noted that most studies to date show the average shrinkage in tumor size varies from 12% to 22% in metastatic renal disease. "The data suggests that these therapies might be helpful for surgeons. At the same time, we have no prospective randomized studies that provide data on this approach yet--just level 2 evidence," he noted.

For further information on targeted therapy in metastatic renal cell carcinoma without cytoreductive nephrectomy, see abstract 4613, being presented June 7 at the ASCO Annual Meeting.

Reference

1. Abel EJ, Tannir NM, Culp SH, et al: Does targeted therapy result in reliable and meaningful primary tumor downstaging in patients with metastatic renal cell carcinoma? 2010 Genitourinary Cancers Symposium. Abstract 318. Presented March 7, 2010.

Barbara Boughton is a freelance reporter based in the San Francisco area and coauthor of Reduce Your Cancer Risk.