May 31, 2013 | by Roberta Nichols
For metastatic kidney cancer patients, research results now being shared at the American Society of Clinical Oncology meeting in Chicago could ultimately have significant impact. One study suggests that, although patients may not have benefited from a specific drug twice before, they may benefit if it's given a third time. A second study suggests that kidney removal could have an important role to play in extending survival, even in this era of targeted drug treatments.
Drug that fails twice could succeed on third try
Patients with metastatic kidney cancer will find encouraging news in the outcomes of a phase III study that explored the effects of the drug Pazopanib in the third-line setting – that is, when patients are given a drug after not responding to it twice before. “In most studies, the response rates – the extent to which the tumor decreases in the third-line setting is pretty limited,” said first author Sumanta Pal, M.D. “But in this study, we had a whopping response rate of 43 percent.” This represented the highest overall response rate observed to date in a third-line trial in metastatic renal cell carcinoma.
The study included 28 patients ranging from ages 45 to 86, whose median age was 63. Besides generating clinical data documenting the effectiveness of this therapy, researchers paid meticulous – and more frequent – attention to biomarkers in the blood. Instead of collecting blood only at the beginning of therapy to try to predict how patients would respond, researchers collected blood samples every month the patients were participating in the clinical trial. “These biomarkers drive resistance,” Pal said. “That probably underscores the greatest novelty of this study. In addition to demonstrating the highest response rate so far that has been identified in a third-line study in kidney cancer, it’s also the first study to look longitudinally at these extended time points for biomarker assays.” At six and 12 months, differences in molecular profiles emerged between patients who responded to the drug and those who did not, potentially underscoring mechanisms of drug resistance. “When you get into six months and 12 months, that’s really when some of these biomarkers start separating out,” Pal added.
Kidney removal could have benefits, even in targeted-drug era
The treatment of metastatic kidney cancer might be divided into the “cytokine” era (1992-2004), when immune-based therapies such as interferon-alpha blasted not only the tumor but surrounding tissue, and the targeted therapy era (2005-2009), when a strategic approach was taken with more discriminating agents such as Sorafenib.
The role of cytoreductive nephrectomy (CN) – removing a kidney in patients with metastatic renal cell carcinoma (mRCC) – was well-defined during the cytokine era. However, its role has been less understood in the era of targeted therapies. “Our study is the first population-based analysis comparing clinical outcomes in association with cytoreductive nephrectomy in the cytokine and targeted therapy eras,” said Rebecca Nelson, a Ph.D. biostatistics staff scientist at City of Hope. Since the onset of targeted therapies, the benefit of CN is murkier because many patients enrolled in clinical trials leading to the approval of targeted agents already had their kidneys removed. “Because of the unclear advantage of cytoreductive nephrectomy in the context of targeted therapies, there is still some debate about whether it should represent a standard of care for patients with metastatic kidney cancer,” she said. “Our results showed that for metastatic kidney cancer patients, those who underwent a nephrectomy in the targeted therapy era survived nearly 30% longer than those who underwent a nephrectomy before targeted therapy was in use – 22 months compared to 17 months,” Nelson said. She and Sumanta Pal, M.D., along with colleagues at the Comprehensive Cancer Centers of Nevada, and the U.S. Oncology Network in Las Vegas, examined data from the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) Database, which houses cancer-related information for 28 percent of cancer patients in the United States. “We looked at patients with kidney cancer who were getting surgery up front; it’s not always the standard of care to get surgery up front, but these patients did,” said Pal, who will be presenting the study at the ASCO meeting, held May 31 through June 4. “We found that surgery seemed to improve outcomes for patients with metastatic kidney cancer. You would think that this surgery to remove the kidney up front probably wouldn’t benefit patients in which disease has spread through their bodies. But the fact is we did find a relatively profound effect,” Pal said. “Going forward, studies that utilize cytoreductive nephrectomy in addition to targeted therapy may help doctors better understand the benefits of this surgery,” Nelson added.