New developments in Advanced Pancreatic Cancer from ASCO GI 2013 – Part 2
Mar01

New developments in Advanced Pancreatic Cancer from ASCO GI 2013 – Part 2

The following is a guest post from Sally Church (known to many in the twittersphere as @MaverickNY), from the Pharma Strategy Blog. In my last post on The Haystack, we discussed the phase III data from the Abraxane MPACT trial in advanced pancreatic cancer that was presented at the recent ASCO GI meeting in San Francisco. Two other late-stage studies in pancreatic cancer caught my eye—fresh data for AB Science’s kinase inhibitor masitinib and Sanofi’s multidrug pill S1. Masitinib is an oral tyrosine kinase inhibitor from AB Science that targets KIT, PDGFR, FGFR3 and has shown activity in gastrointestinal stromal tumours (GIST). A different version of the drug (Masivet, Kinavet) is also approved in France and the US for the treatment of a dog mast cell (skin) cancers, which are also known to be KIT-driven. S1 is multidrug pill from Sanofi and Taiho that consists of tegafur (a prodrug of 5FU), gimeracil (5-chloro-2,4 dihydropyridine, CDHP) which inhibits dihydropyrimidine dehydrogenase (DPD) enzyme, and oteracil (potassium oxonate, Oxo), which reduces gastrointestinal toxicity. Previous Japanese studies have demonstrated effectiveness of this agent in gastric and colorectal cancers, so a big unaswered question is whether it is effective in pancreatic cancer. So what was interesting about the latest data at this meeting? At the ASCO GI conference in 2009, French oncologist Emmanuel Mitry presented data from a small Phase II study of the effect of combining masitinib and Eli Lilly’s Gemzar in advanced pancreatic cancer. The study had just 22 patients, but the median overall survival of 7.1 months in was not a large improvement over what is often seen with the standard of care, Gemzar given alone, or with a combination of Gemzar and Genentech’s Tarceva. Over the years, many combination therapies based on Gemzar have failed to show superiority over single agent therapy. It’s both a high unmet medical need and a high barrier to beat.  Thus, the phase III data for the combination of masitnib and Gemzar was highly anticipated at this year’s ASCO GI meeting. Gael Deplanque and colleagues compared masitinib plus Gemzar to Gemzar plus placebo.  Although the overall trial results for median overall survival were slightly higher than in the phase II study, they were not significant (7.7 versus 7.0 months, P=0.74; HR=0.90). Some promising data was observed, however, in a subset of the population identified by a profile of biomarkers that the authors vaguely described as, “a specific deleterious genomic biomarker (GBM) consisting of a limited number of genes.” No other details on the actual genes or biomarkers were was provided, but the subset was described as having an improved MOS to 11.0 months compared to the Gemzar...

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