ORLANDO—Sunitinib improves overall survival while offering a superior quality of life (QoL) compared with interferon-α (IFN-α) as first-line therapy for metastatic renal cell carcinoma (RCC), data show.

In a phase 3 study, sunitinib more than doubled progression-free survival (PFS) compared with IFN-α (median 11 vs. 5 months). The median overall survival was 26.4 months for sunitinib-treated patients compared with 21.8 months for IFN-α recipients.

“This is the first time overall survival of more than two years has been shown in the treatment of advanced kidney cancer,” said lead investigator Robert J. Motzer, MD, Attending Physician at Memorial Sloan-Kettering Cancer Center in New York City.

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“These data demonstrating the efficacy of sunitinib and its impact on patients’ perception of their overall health underscore the significant role sunitinib has played in changing the way we approach this disease.” Findings were presented here at the American Society of Clinical Oncology Annual Meeting.

Until 2005, treatment options for this patient population were limited to cytokines, such as IFN-α, which are often associated with side effects not tolerated by significant numbers of patients.

Dr. Motzer’s group studied 750 patients with previously untreated advanced RCC and randomized 375 to receive sunitinib 50 mg daily and 375 to receive IFN-α 9 mU three times a day.

Based on improved PFS observed at the second interim analysis in 2006, the Data Safety Monitoring Board recommended the study protocol be amended to allow patients in the IFN-α  arm to cross over to treatment with sunitinib when their disease progressed. Twenty-five patients in the IFN-α  arm (7%) crossed over to the sunitinib arm.

Sunitinib was associated with significant improvement in investigator-assessed objective response rate, a secondary study end point. By this assessment, 47% of sunitinib-treated patients had responded to treatment compared with 12% of IFN-α recipients. Eleven patients in the sunitinib arm had a complete response vs. only four in the IFN-α group.

The most commonly reported grade 3-4 adverse events in the sunitinib group were hypertension (12% of subjects), fatigue (11%), diarrhea (9%), hand-foot syndrome (9%), asthenia (7%), and nausea (5%). Overall the sunitinib group reported lower severity of disease-related symptoms, including lack of energy, weight loss, fatigue, breathlessness, coughing, and fever at each treatment cycle compared with patients receiving IFN-α.

All patients were asked to complete validated questionnaires to measure QoL, a secondary end point of the trial. Questionnaires were completed on days 1 and 28 of each 42-day treatment cycle and at the end of treatment or at withdrawal from the study.

“We found that from the quality-of-life perspective, sunitinib was superior to IFN-α across the board in terms of patients’ symptoms and general well-being,” said co-investigator David Cella, PhD, Professor of Psychiatry and Behavioral Science at Northwestern University, Feinberg School of Medicine, in Chicago.

“In my mind, [the study findings] clarify that interferon has been replaced by agents like sunitinib as first-line treatment for metastatic renal cancer. I think that is good news for patients because they now have a more effective and less toxic alternative for treatment.”

He and his colleagues found no significant differences when they compared QOL of patients in the United States with similar patients on sunitinib for metastatic RCC in France, Germany, Italy, Poland, Spain, and the United Kingdom.

“The side effects are manageable. You do see a problem with rashes and diarrhea and the typical side effects. However, they have far less impact on the patient’s function and quality of life,” said Dr. Cella told Renal & Urology News. “You don’t see the dramatic flulike symptoms and fatigue with this agent that you get with something like interferon.”