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PFS may be surrogate endpoint in advanced RCC
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PFS may be a viable surrogate endpoint for OS in patients with metastatic renal cell carcinoma treated with bevacizumab and interferon-alpha, according to results of a phase 3 study.
Researchers evaluated data from two prospective phase 3 trials — CALGB and AVOREN — that included 1,381 patients with previously untreated clear cell metastatic renal cell carcinoma (mRCC).
All patients had an ECOG performance status of 0 to 2. In addition, they had adequate bone marrow, hepatic, cardiac and renal function, and their blood pressure was under control.
The CALGB and AVOREN trials evaluated the use of interferon-alpha with or without bevacizumab (Avastin, Genentech).
For the purpose of the current study, CALGB served as the training data set and AVOREN served as the testing data set. Researchers assessed the dependence between PFS and OS in patients with mRCC and to find if PFS can be used as an intermediate endpoint of OS.
In the training data set, researchers calculated the following median OS times:
- 6 months for patients who experienced disease progression within 3 months;
- 8 months for patients who experienced disease progression within 6 months;
- 25 months for patients who did not experience disease progression within 3 months; and
- 30 months for patients who did not experience disease progression within 6 months (P<.001 for all).
Researchers conducted adjusted HRs of 2.6 (P<.001) for patients who did not progress within 3 months and 2.8 (P<.001) for patients who did not progress within 6 months.
The dependence between PFS and OS was 0.53, and the associations were confirmed in the testing data set, according to the researchers.
“A high dependence between PFS and OS was observed, suggesting that PFS may be used as a surrogate endpoint for OS,” the researchers wrote. “Although this is a novel observation for renal cell carcinoma, these findings require validation in patients with metastatic renal cell carcinoma who are treated with other targeted agents.”
In an accompanying editorial, Andreas Becker, MD, of the department of urology at the University Hospital Hamburg-Eppendorf in Hamburg, Germany, and colleagues wrote: “Because only 49% of all patients in the CALGB trial received secondary treatments, the association between PFS and OS needs to be confirmed in contemporary patients who are typically receiving a sequential therapy of multiple biologically active agents. A rigorous evaluation of this topic is needed before PFS can be reliably considered to be a valid surrogate endpoint of OS in patients with mRCC.”
For more information:
- Becker A. Cancer. 2013;doi:10.1002/cncr.28378.
- Halabi S. Cancer. 2013;doi:10.1002/cncr.28221.
Disclosure: The researchers report research funding, grants, consulting fees, honoraria and travel support from Aveo, Bristol-Myers Squibb, GlaxoSmithKline and Pfizer. They also report consultant roles with Aveo, Bayer, Genentech, GlaxoSmithKline, Novartis, Pfizer and Roche.