Clinical Newswire, August 1, 2009-Final results from a Phase III trial directly comparing sunitinib and interferon alfa as first-line treatment in patients with metastatic renal cell carcinoma show that sunitinib is associated with increased survival. The results, published in the August 2009 edition of the Journal of Clinical Oncology, highlight an improved prognosis for this hard-to-treat patient group.
Renal-cell carcinoma (RCC) is highly resistant to chemotherapy treatment and interferon alfa has widely been seen as first-line treatment for metastatic disease. The tyrosine kinase inhibitor sunitinib was also recently demonstrated to have a high response rate in the second-line RCC treatment setting.
Interim results from the trial directly comparing the two drugs, led by Robert J. Motzer of the Memorial Sloan-Kettering Cancer Center, were initially presented at the 44th Annual Meeting of the American Society of Clinical Oncology in June, 2008, and at that time showed the superiority of sunitinib over interferon alfa in progression free survival (PFS) (11 months vs. 5 months, respectively, P<0.001). The current publication describes final overall survival analyses, and updated efficacy and safety results.
Seven-hundred and fifty patients with treatment-naive metastatic RCC were randomized into sunitinib (50mg administered orally once daily on a 4 weeks on-2weeks off dosing schedule) and interferon alfa (9MU administered subcutaneoulsly thrice weekly) treatment groups. Patients in each group had received at least one dose of sunitinib or interferon alfa, respectively. Baseline characteristics between each group were similar.
Primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. Median treatment duration was 11 months in the sunitinib group and 4 months in the interferon alfa group.
Patients given sunitinib had a significantly higher ORR (47%; 95% CI, 42%-52%) than those given interferon alfa (12%, 95%CI, 9%-16%, P<0.001). Complete response was seen in 11 patients in the sunitinib group and 4 patients in the interferon alfa group. Median PFS in the sunitinib group was 11 months (95%CI, 11-13 months) and 5 months (95%CI, 4-6 months) in the interferon alfa group (HR=0.539;95%CI, 0.451-0.643; P<0.001).
Median OS was also significantly higher in the sunitinib group vs. the interferon alfa group, at 26.4 months (95%CI, 23.0-32.9 months) vs. 21.8 months (95%CI, 17.9-26.9 months), respectively (HR=0.818; 95%CI, 0.669-0.999; P=0.049).
When baseline clinical characteristics and previously identified prognostic risk factors were analyzed by a Cox proportional hazards model, sunitinib was also found to be superior over interferon alfa in nearly every patient sub-group. ECOG performance status, serum hemoglobin, time from diagnosis to treatment, corrected calcium, alkaline phosphatase, lactate dehydrogenase, and number of metastatic sites, were all found to be significant independent predictors for survival.
Grade 3 and 4 adverse events (AE) in both groups were relatively low. Treatment-related adverse events (AE) occurred more frequently in the sunitinib group compared to the interferon alfa group, including ejection fraction decline (13% vs. 3%, respectively) and hypothyroidism (14％ vs. 2%, respectively). Discontinuation due to adverse events numbered 19% in the sunitinib group and 23% in the interferon alfa group. Deaths, primarily from disease progression, totaled 23 for the sunitinib group and 20 for the interferon alfa group. According to investigator assessment, 3 deaths were considered treatment-related; 1 in the sunitinib group and 2 in the interferon alfa group (one each of cardiac disorder and myocardial infarction). The most common sunitinib-related grade 3 AE were hypertension (12%), fatigue (11%), diarrhea (9%) and hand-foot syndrome (9%).
The authors concluded that sunitinib significantly improves OS compared to interferon alfa, has an acceptable safety profile, and is also associated with improved response and PFS. Sunitinib has been recommended for first-line treatment in patients with metastatic RCC.
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