AB Science, the manufacturer of masitinib, issued a press release in Paris 1/19/2011 referring to a Phase 2 trial of masitinib versus sunitinib in resistant GIST.
http://www.investegate.co.uk/Article.aspx?id=20110120082650P0002 also indicates that a trial of masitinib versus sunitinib in imatinib-resistant GIST patients is beginning, but no trial ID number or details are yet available on clinicaltrials.gov.
The trial described is not listed in clinicalTrials.gov nor is it listed in the European clinical trial registries.
Here is a link to the poster presented this month: http://www.ab-science.com/file_bdd/1295456962_ascogi2011blayetal.pdf
From the press release:
"Masitinib is also being developed for patients resistant to imatinib (Glivec(r))in an on-going phase 2 study, which is comparing masitinib to the approved second line drug, sunitinib (Sutent(r)). Results should be available in 2012. Key variables assessed are overall survival and PFS."
"Characteristics of the phase 2 in Second line treatment of GIST: A prospective, multicenter, randomized, open-label, active-controlled, 2-parallel group, phase II study to compare efficacy and safety of Masitinib at 12 mg/kg/day to sunitinib at 50 mg/day in treatment of patients with gastro-intestinal stromal tumor resistant to imatinib
Patients will be randomized in two groups:
- Group 1: Patients will receive masitinib at 12 mg/kg/day
- Group 2: Patients will receive sunitinib at 50 mg/day
The primary criterion will be the Overall Progression Free Survival (PFS), defined as the delay between the date of randomisation to the date of documented progression or any cause of death during the study. Overall Survival will be the main secondary criterion."
FROM MARINA 1/30/11:
I noticed from the masitinib poster that no one in the trial's 30 patients had an exon 9 KIT mutation, a mutation associated with faster progression for imatinib. The exon 9 mutation occurs normally at a frequency of about 10% of a large population of GIST pts.
The masitinib trial also had a higher than normal percentage of pts with a PDGFRA mutation (unspecified type), WT, and a dual exon 11 plus exon 13 mutation.
In short, the data from 30 pts might not provide a good representation of a large population of GIST pts.
I think we would be comparing red delicious apples on masitinib versus gala apples on imatinib.
But they are doing a large randomized trial of the two drugs, and in this trial both patient arms should be equivalent regarding mutations, and then we will be comparing red delicious apples on masitinib versus red delicious applies on imatinib.
It is also used to treat mastocytosis in dogs, so it is a veterinary product. This shall make very interesting the pricing strategy for human use, I think.
"animal medicine trade name Masivet® in Europe" http://www.masivet.com/
One good thing about masitinib is that it does not inhibit ABL and therefore should not have any heart-related side effects. Neither does it inhibit VEGF or its receptors. It may inhibit KIT more strongly than immatinib, but the proof of the pudding will be in the current trial.
AB Science, developer of MASITINIB, tells us that the trial comparing SUNITINIB versus MASINITIB in IMATINIB RESISTANT patients is being done only in France. It will be very interesting to see how this one turns out, as masitinib may have equal or better effectiveness (this is unknown) with fewer side effects than sunitinib (this is fairly certain).
The first-line trial comparing MASINITIB versus IMATINIB in NEWLY DIAGNOSED UNRESECTABLE patients and newly-recurrent patients is available at a number of US locations.
http://clinicaltrials.gov/ct2/show/study/NCT00812240?term=masitinib+GIST&rank=1&show_locs=Y#locn The initial eligibiilty criteria are:
1.Histologically proven, metastatic or locally advanced non resectable, or recurrent post surgery GIST
2.Naïve patient or patient previously treated with imatinib as neoadjuvant/adjuvant who relapsed after imatinib discontinuation
3.C-Kit (CD117) positive tumours detected immuno-histochemically or PDGF positive if c-kit negative
PRESS RELEASE 02/01/2012
""In this study, 44 patients with inoperable, locally advanced or metastatic GIST and showing disease progression while treated with Gleevec(R) (imatinib) (400 to 800 mg/day) received either masitinib (23 patients) at 12 mg/kg/day or Sutent(R) (21 patients) until progression. After a median follow-up of 14 months, median overall survival was not reached for masitinib versus 15 months for Sutent(R) (p=0.022 hr:3.2). After 18 months, 79% of patients treated with masitinib were still alive, versus 20% for patients treated with Sutent(R). After 2 years, 53% of patients treated with masitinib were still alive, versus 0% for the patients treated with Sutent(R). ""
""The study also demonstrated that masitinib was significantly better tolerated than Sutent(R). The safety profile of masitinib was better than that of sunitinib, with a significantly longer Safety Event Free Survival (p=0.002), and a lower occurrence of severe adverse events. In masitinib treated patients, nausea, diarrhea and asthenia were the most common related adverse events. Full data has been submitted for publication to the American Society of Clinical Oncology (ASCO) 2012 Annual Meeting.
Axel Le Cesne, MD (Institut Gustave Roussy, France), the principal investigator of this study declared: "Given this substantial advantage in survival coupled with lower toxicity of masitinib as compared with Sutent(R), we believe that masitinib is an important step forward in the treatment of GIST."
Masitinib is a drug already on the market for your dog. It is a veterinary product used to treat mastocytosis in dogs. A small study of 44 pts showed some impressive results (below) for Gleevec resistant GIST.
""After 18 months, 79% of [Gleevec resistant] patients treated with masitinib were still alive, versus 20% for patients treated with Sutent(R).""
Always be mindful that press releases about a drug are often drafted by the company itself. Also understand how the word "significant" is used in statistics and press releases and media reports about clinical trials. "Significant" means the results probably did not happen by random chance. It does not one way or another mean that the results had practical importance. For example, there have been cases where a drug "significantly imrpoved overall survival" by two weeks. This means the results did not happen by random chance in the study sample, but no patient would think it was practically important. The results below for masitinib, however, do seem practically important...a pretty big advantage over Sutent. A larger trial would be needed to know if the results bear out.