Two widely used targeted-therapy drugs approved by the FDA for the treatment of metastatic kidney cancer—sorafenib (Nexavar, Bayer/Onyx Pharmaceuticals) and sunitinib (Sutent, Pfizer)—are no more effective than a placebo in preventing return of the disease, according to a new study from the Abramson Cancer Center (ACC) of the University of Pennsylvania.

The investigators treated 1,943 patients in the U.S. and Canada with one year of sorafenib, sunitinib, or a placebo after surgery to remove their kidney tumors. The phase 3, randomized, double-blind study, published in the Lancet, found no significant difference in the median years of disease-free survival in the adjuvant setting (post-surgery): 5.8 years for sunitinib; 6.1 years for sorafenib; and 6.6 years for placebo.

While surgery is typically the best initial treatment for renal tumors, surgical resection alone is not enough to prevent the return of the disease in many patients. Adjuvant therapies are often needed to improve survival.

The kinase inhibitors sunitinib and sorafenib are commonly used adjuvant therapies for patients with renal cancer. Kinases are proteins on or near the surface of cancer cells that help the cells grow and survive. Kinase inhibitors block the growth of kinases and associated blood vessels that nourish cancers. Sorafenib and sunitinib, which are taken in pill form on a daily basis, are thought to block different kinases. Both drugs have been shown to be effective against metastatic renal cancer, but the authors wanted to find out if they also could be effective in preventing disease recurrence.

“The current standard of care for these patients is close observation,” said lead investigator Naomi B. Haas, MD, an associate professor in the division of hematology/oncology at the Perelman School of Medicine and director of the prostate and kidney cancer program at the ACC. “Unfortunately, we found that the use of sunitinib or sorafenib in this setting did not reduce the incidence of recurrence as compared to placebo. Fortunately, the use of these drugs in this setting did not appear to make the outcome of patients receiving them any worse.”

The findings mirror those of adjuvant trials in other tumors, such as breast and metastatic colorectal cancers, in which the benefits of bevacizumab in metastatic disease were not seen in the adjuvant setting.

The new study was the first and largest trial to investigate the effectiveness of these two kinase inhibitors in patients whose kidney tumors have been completely removed and who were at high risk for recurrence. Haas said that other ongoing adjuvant trials are investigating different lengths of therapy with sunitinib and sorafenib, as well as different kinase inhibitors. The results of these investigations are not yet available and could differ from those of the Penn study, she said.

During the early years of the trial, approximately one-third of the patients stopped treatment with sunitinib or sorafenib because they found the adverse effects of the medications, such as hypertension and fatigue, to be too difficult to tolerate.

Patients in the study also contributed blood and urine samples as a part of their participation. Ongoing analyses of these samples may shed light on who could still benefit from sunitinib or sorafenib in the treatment of kidney cancer in the adjuvant setting, or the analyses may point to other therapies that target specific pathways or tap into the immune system, according to the authors.

Haas and her colleagues collected the samples at the beginning of treatment and after the recurrence of cancer in patients who experienced a relapse—and continue to do so more than five years after the formal conclusion of the study.

“This will afford opportunities to uncover molecular clues and other information that could help explain why some patients had a recurrence of their cancer or a spreading elsewhere and others did not,” Haas said.

A perioperative trial with an immune checkpoint inhibitor in this group of patients is set to open in the near future.

Source: University of Pennsylvania; March 9, 2016.

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