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Proposal 675

Title of the Proposed Research

Validation study on magnitude of tumor shrinkage as a prognostic marker

Lead Researcher

Viktor Grünwald, MD

Affiliation

Medical School Hannover
Hannover, Germany

Funding Source

None

Potential Conflicts of Interest

Lead Researcher: Consultancy: GSK, Pfizer, Novartis, Astellas, Mologen, Bayer Lectures: GSK, Pfizer, Novartis, Astellas, Bayer

Researcher 1: None

Management of Real or Potential Conflicts of Interest
Disclosure of interests when the research is presented and published.

Data Sharing Agreement Date

3 Dec 2014

Lay Summary

Since the introduction of targeted therapies for cancer treatment the role of objective response rate (ORR) has been questioned for its clinical relevance. We recently published the lack of correlation between ORR and prognosis in a retrospective series in mRCC (Busch et al. European Journal Cancer 2013; doi:10.1016/j.ejca.2013.10.017). However, tumor shrinkage of at least 10% occurring within 3 months of treatment has been associated with over all survival (OS) in another retrospective series by our group (Seidel C. et al. (2013). Br J Cancer doi:10.1038/bjc.2013.662).

In order to explore whether the extent of tumor shrinkage correlates with distinct clinical outcomes, we investigated this question in a Pfizer pooled clinical trial population of mRCC treated in 1st or 2nd line with various agents. A total of 2749 pts. have been analyzed for that purpose. Pts were characterized by maximal tumor shrinkage from baseline (-100% to <-60%, =60% to <-30%, =-30% to <0%, =0 to <+20%, =+20%). Kaplan Meier (K-M) plots have been used for OS estimates and a Cox proportional hazard analysis with 6 months landmark showed its role as an independent prognostic marker (Grünwald et al. ESMO 2013 #2702). If validated, this finding could set a benchmark for early clinical trial endpoints in mRCC.

The aim of the current study is to validate these findings by K-M plots and Cox-proportional hazard analysis (6 mo. landmark) with data from the COMPARZ trial. Furthermore, the role of tumor shrinkage at 3 months will be assessed as a putative early endpoint in clinical trials. Because the depth of remission has been shown to be a prognostic factor in our analysis, COMPARZ provides the only prospective data with head to head comparison of sunitinib and pazopanib. Despite the similar ORR for these agents, their ability to induce deep remission remains unknown.

Study Data Provided

Study VEG105192: A Randomised, Double-blind, Placebo controlled, Multi-center Phase III Study to Evaluate the Efficacy and Safety of Pazopanib (GW786034) Compared to Placebo in Patients with Locally Advanced and/or Metastatic Renal Cell Carcinoma
Study VEG108844: A study of Pazopanib versus Sunitinib in the Treatment of Subjects with Locally Advanced and/or Metastatic Renal Cell Carcinoma

Statistical Analysis Plan

This will be added after the research is published.

Publication Citation