CTOSFrom October 30th to November 2nd the Life Raft Group staff members attended the annual Connective Tissue Oncology Society (CTOS) Meeting in New York City. In addition to a number of presentations relevant to GIST, the LRG also took part in some very significant meetings with some of the world’s leading GIST experts.

Perhaps the highlight of the meeting from a GIST perspective was the GIST presentation session that took place Saturday afternoon. The session featured a number of relevant presentations:

The role of ABL1 in the therapeutic response of GIST cells to imatinib mesylate – Dr. Anette Duensing of the University of Pittsburgh, who is a member of the LRG Research Team, did this presentation. She noted that imatinib inhibits both KIT and ABL1, but inactivation of ABL1 in turn activates PI3K, which makes imatinib less effective. The implication of the study was that in order to make future therapies that are more effective for GIST, it would be best to develop a KIT inhibitor that does not also inhibit ABL1.

Long-term analysis of a phase III randomized, intergroup, international trial assessing the clinical activity of imatinib at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors (GIST) – Dr. Paolo Casali of the Istituto Nazionale dei Tumori in Milan, Italy, conducted this presentation. The presentation reported on a long-term study (median follow-up = 10.9 years) comparing patients with advanced disease on 400 mg of imatinib with those on 800 mg. Patients in the 400 mg arm were allowed to cross over into the 800 mg arm if they had progression. The intent of the study was to determine what prognostic factors existed for GIST patients. While dosage was not found to be a statistically significant factor, KIT mutational status (mutations other than exon 11 had worse outcomes) and diameter of the largest tumor (larger tumors had worse outcomes) were significant. When summing up the data, Dr. Casali cautioned, however, that, “We may not be looking at the whole curve, but instead just the top tail of it.” He implied that perhaps the patients in this study may not be completely representative of all GIST patients.

Tolerability and anti-tumor activity of the PI3K/MTOR inhibitor GDC-0980 in patients (PTS) with GIST and other SARCOMAS on two phase I studies – Dr. Andrew Wagner of Dana-Farber conducted this presentation that examined a drug from Genentech. This early study examined different dosage schedules (daily and weekly) and levels (2-70 mg daily, 6-200 mg weekly) in an attempt to assess safety and tolerability, PK values, and anti-tumor activity. A number of different sarcomas were featured in the study, including 11 patients with GIST. The study found that the drug was well tolerated in GIST patients, and patients did have disease control greater than those on placebo. The authors believe that this compound warrants further study in GIST patients.

Interim analysis of SARC022, a phase II study of Linsitinib in pediatric and adult wild type (WT) gastrointestinal stromal tumors) – This presentation, conducted by Dr. Margaret von Mehren of Fox Chase Cancer Center in Philadelphia, reported on the ongoing trial for linsitinib, a drug aimed at pediatric and wild type patients.  The study met its first stage accrual target of 20 patients (12 female, 8 male), and per the authors, “demonstrates that studies evaluating agents in Wild-Type GIST can be performed.” The drug seemed to be well tolerated, and 55 percent of the patients in the trial had stable disease six months or longer at the time data was collected. As the trial is ongoing, we will be sure to report further results when they are released.

Dr. Jon Trent of Sylvester Cancer Center in Miami was the discussant and summarized all of the presentations quite well. He pointed out that they complemented each other by showing that there are a number of different forms of GIST that vary by mutation, exon, and expression of particular factors like IGF-1R, and that this shows us that these different forms of the disease need to be handled differently in regards to specific drugs and dosage levels.

In addition to the presentations, the LRG had a number of meetings with key GIST experts. Drs. Jon Trent of the U.S., Peter Reichardt of Germany, Matias Chacon of Argentina, and Yoon-Koo Kang of South Korea all met with the LRG to discuss various ongoing projects. All of these doctors also were confirmed as the inaugural members of the LRG’s GIST Medical Team – a group of experts throughout the world that the LRG will consult with on various topics related to GIST. In addition, each of these doctors confirmed their participation in the GIST Cancer Journal, the first scholarly journal devoted solely to GIST, which will be released in the coming months.

Along with meeting with the GIST Medical Team, the LRG also met with Dr. Lee Helman of the NIH to discuss a project designed to help our pediatric patients. Dr. Helman also updated us, telling us that the term “pediatric GIST” is no longer being used, but has instead officially been changed to “SDH-deficient GIST.”

Our final meeting was with two members of the LRG Research Team, who updated us on their research progress.  Keep an eye out in the coming months, when we will further update you not only on their progress, but also that of the rest of the research team, and how we can help them continue that progress.

All in all, this year’s CTOS meeting was a very productive one for the LRG. Watch for news from us in the months ahead where we will update you on a number of new projects we are currently working on, and also on any updates on the research presented at CTOS and elsewhere.