PFS May Be Valid Surrogate Endpoint for Overall Survival in Metastatic RCC

October 18, 2013

Results of a recent study indicate that patient progression-free survival at 3 months and 6 months was predictive of the overall survival among metastatic RCC patients treated with interferon alpha and bevacizumab.

[[{"type":"media","view_mode":"media_crop","fid":"18024","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_786211784522","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"1207","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":"Pulmonal multinodular metastasis of a renal cell carcinoma.","typeof":"foaf:Image"}}]]Results of a recent study indicate that patient progression-free survival at 3 months and 6 months was predictive of the overall survival among patients with metastatic renal cell carcinoma treated with interferon alpha and bevacizumab.

Based on these results, the researchers led by, Susan Halabi, PhD, of Duke University Medical Center, concluded that “progression-free survival may be an appropriate intermediate endpoint for overall survival,” but cautioned that the results need to be further validated in other patients treated with VEGF-directed therapies.

Halabi and colleagues undertook this study to establish if progression-free survival was a reliable surrogate endpoint in metastatic renal cell carcinoma. Many of the recent approvals of drugs to treat renal cell carcinoma were based on clinical trials that showed significant improvements in progression-free survival; however, “the association between progression-free survival and overall survival is not a foregone conclusion … because the development and approval of a large number of agents targeting similar pathways have created the potential for a significant number of postprogression therapies that may confound and attenuate treatments effects on overall survival in phase III trials,” the researchers wrote.

This study included 1,381 patients with metastatic renal cell carcinoma taken from two phase III trials looking at interferon alpha with or without bevacizumab. Patients were previously untreated and had ECOG performance status of 0 to 2. The median follow-up was 62 months among patients taken from the CALGB 90206 trial, and was 39 months among patients taken from the AVOREN trial. The results of the study were published in Cancer.

Patients from the CALGB trial were used as the training data set. Among these patients, the median overall survival among patients who did not progress at 3 months was 25 months compared with an overall survival of 6 months among patients whose disease had progressed by that time point (P < .0001).

When looking at data from AVOREN, the median overall survival among patients who did not progress was 26 months compared with 6 months among those that did (P < .0001).

Patients who progressed had an adjusted hazard ratio for death of 2.6 in the CALGB trial and 3.4 in the AVOREN trial compared with those who did not, indicating that disease progression at 3 months predicted overall survival.

The researchers found similar results when looking at progression at the 6-month mark as well.

“Before this analysis, the usefulness of progression-free survival as a potential intermediate endpoint for overall survival in patients with metastatic renal cell carcinoma has been called into question,” the researchers wrote. “Although some investigators have made similar claims in the past, to our knowledge this is the first formal statistical analysis of prospectively obtained clinical trial data supporting such a view and supports the regulatory agency approval of bevacizumab as a useful therapy in patients with metastatic renal cell carcinoma.”