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Validation study on magnitude of tumorshrinkage as a prognostic marker

Validation study on magnitude of tumorshrinkage as a prognostic marker

Viktor Grünwald

Medical School HannoverHannover, Germany


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

17 October 2014

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.

[{ "PostingID": 4164, "Title": "NOVARTIS-VEG105192", "Description": "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" }]

Statistical Analysis Plan

V. Grünwald, M. Dietrich, G.R. Pond. 2016 Annals of Oncology 27(suppl_6). 817P - Prognostic ability of HR-QoL parameters in metastatic renal cell carcinoma (mRCC).

M.J.Sorich, A.Rowland, G.Kichenadasse, R.J.Woodman, A.A.Mangoni. British Journal of Cancer volume 114, pages 1313-1317 (2016). Risk factors of proteinuria in renal cell carcinoma patients treated with VEGF inhibitors: a secondary analysis of pooled clinical trial data.
DOI: 10.1038/bjc.2016.147