Long-term results from Southwest Oncology Group trial S8949 confirm the original study finding that performing palliative debulking surgery prior to starting systemic therapy with interferon alfa-2b confers a survival benefit in patients with advanced renal cell carcinoma.
Chicago-Long-term results from a Southwest Oncology Group trial confirm the original study finding that performing palliative debulking surgery prior to starting systemic therapy with interferon alfa-2b confers a survival benefit in patients with advanced renal cell carcinoma, researchers reported at the American Society of Clinical Oncology annual meeting.
The study, S8949, was launched in 1991, and randomized 246 patients who were acceptable candidates for nephrectomy into the two treatment arms. In the initial publication of the study outcomes (N Engl J Med 2001; 345:1655-9), median follow-up was about 1 year. Median overall survival was significantly longer in the nephrectomy group than among patients treated only with systemic therapy: 11.1 versus 8.1 months.
In the current report, median follow-up was 9 years, and the patients randomized to nephrectomy again had a significantly longer median overall survival relative to those treated with interferon alone (11 vs. 8 months, hazard ratio: 0.74; p=.021). The significant benefit of nephrectomy for prolonging survival extended across all predefined patient strata, which categorized patients by performance status (PS 0 or 1), presence or absence of lung metastases, and presence or absence of at least one measurable metastatic lesion in the region not to be resected.
Patients enrolled in the study had a median age of 59 years, almost 70% were men, and those with PS of 0 or 1 were about equally represented. About two-thirds of patients had lung metastases only, and about three-fourths of patients had measurable metastatic disease.
Post hoc analyses were performed using Cox regression models to determine clinical variables that predicted survival outcomes. In univariate analysis, significantly poorer survival was seen in patients with a PS of 1 versus 0 (p<.0001), hemoglobin below versus above the median (p=.015), and those with early progression within 90 days (p<.0001), who represented about one-third of the cohort.
In multivariate analysis, early progressive disease (p<.0001) and PS of 1 (p=.0006) were the only independent predictors of survival, with hazard ratios of 1.7 and 2.10, respectively.
Patients in the interferon-only group without early progression had a significantly better median overall survival than patients who underwent nephrectomy, but who had early progression (14 vs. 5 months, respectively).
"Assessment of candidate prognostic and predictive factors is potentially useful for patient care and when enrolling patients in clinical trials," Dr. Conlon said. "The database from this collaborative trial provided a good resource to evaluate clinical biomarkers. Hopefully, its results will spur further studies to identify clinical or molecular biomarkers of early progression as these patients may not be benefiting from nephrectomy or interferon therapy,"