An overview of CTOS 2005

The Life Raft Group staff headed to Boca Raton, Fla., Nov. 19-21 to attend the 11th annual conference of the Connective Tissue Oncology Society (CTOS). Here is the news of interest to GIST patients.

 GENERAL SESSION

The status of two series of patients undergoing surgery after Gleevec was reported at the meeting. While we are going to report those results this month, we hope to do a follow-up story soon in which we will report on other similar series as well as getting some comments from the doctors involved. This is an important topic and one that is difficult to evaluate in clinical trials. For the foreseeable future, it is likely that patients and doctors will have to evaluate the advantages and disadvantages of surgery after Gleevec by considering data from available various sources.

Surgical Management of GIST following treatment with KIT-directed chemotherapy — Abstract 459, Chandrajit P. Raut, et al (Brigham and Women’s Hospital, Boston, Mass.

A series of 69 GIST patients had surgery for advanced GIST while receiving KIT-directed therapy. Nine patients had primary tumors only, and 60 had metastatic disease. The groups of patients were:

• 23 patients with unresectable primary/ metastatic GIST following maximum drug response (stable disease).
• 32 patients with metastatic GIST with localized progression while still receiving KIT-directed therapy (limited progression).
• 14 patients with metastatic GIST with generalized progression while still receiving KIT-directed therapy (general progression also known as systemic progression).

These three groups of patients were also categorized by surgical result: no evidence of disease (NED), minimal/ moderate residual disease, and bulky residual disease. Following surgery, 39 percent of patients were NED, 43 percent had minimal/moderate residual disease, and 17 percent had bulky residual disease.

Those patients having stable disease or limited progression prior to surgery were more likely to be NED or have minimal/moderate disease after surgery than those having generalized progression before surgery (89 percent vs. 57 percent).

The median progression-free survival (PFS) was longer for patients who were NED or had minimal/moderate disease versus those with bulky disease (12 months vs. 3 months).

The authors concluded: “Patients with advanced GIST exhibiting stable disease or limited progression on KITdirected therapy were more likely to have successful debulking procedures. Patients who were NED or had minimal/ moderate disease after surgery had improved PFS.”

Advanced Gastrointestinal Stromal Tumor: Molecular, Pathological and Clinical Pattern in Post-imatinib Surgery — Abstract 399, A Gronchi, et al, Istituto Nazionale per lo studio e la cura dei Tumori, Milan, Italy.

This study looked at pathological and molecular features of GIST after treatment with Gleevec. Perhaps even more importantly, they looked at how well GIST patients taking Gleevec did after surgery. Thirty-six out of 162 patients in this group underwent surgery. They were then divided into three groups:

Group A had 25 patients whose cancer was still responding to Gleevec. All of the patients in this group were alive 24 months after surgery and 72 percent had not had progression during those 24 months. Gleevec failed four patients 16 to 18 months after surgery (two of three who had stopped taking Gleevec, and two of the 22 who continued taking Gleevec).

Group B had eight patients with either primary progression or secondary progression. All had disease progression at 12 months and only half were still alive.

The authors concluded: “This series suggests not to discontinue imatinib after surgery, even if complete. Prognostic advantage from surgery of residual disease in response is left to elucidate by combining available series. Neoadjuvant imatinib in bulky primary disease is beneficial. Progressive disease should be treated with second-line molecular-targeted therapies, surgery being likely of minimal benefit.”

ONGOING TRIALS REVIEWED

A very short summary of ongoing (mostly adjuvant Gleevec) trials was presented by a number of different organizations. The general trend seemed to be that adjuvant GIST trials continued to accrue patients at or above expected rates.

The ACOSOG (American College of Surgeons Oncology Group) Z9000 trial is closed. The first interim analysis is expected in 2006.

The Z9001 has been expanded from 489 patients to 732 patients. This was required because they were recruiting more patients in the lower risk categories than expected.

The Spanish sarcoma group Grupo Espanol de Investigacion en Sarcomas (GEIS) has opened a sarcoma and GIST registry at www.registrogeis.com. They have a doxorubicin-plus-Gleevec trial for refractory GIST, and are also participating in the European Organization for Research and Treatment of Cancer (EORTC) 62024 adjuvant Gleevec trial.

The Scandinavian group has an adjuvant trial (SSG XVIII) for high-risk GIST. This trial compares one year of Gleevec versus three years of Gleevec and is being conducted in cooperation with the German group.

The Italian Group has an “observational” study called GIOTTO (GIST Optimal Treatment and Therapy Outcome). They also have a phase II trial of PTK787 (a KIT/VEGF inhibitor made by Novartis) for GIST patients refractory to imatinib. Ongoing Italian clinical protocols can be found on the web at: www.istitutotumori.mi.it/INT/ struttura/pdf2004/Protocolli.pdf.

The Radiation Therapy Oncology Group S-0132 trial is almost full (accrued 55 of 63 patients). This phase II trial is for neoadjuvant/adjuvant Gleevec for primary and recurrent operable GIST expressing CD117. More information about this study can be found at: www.clinicaltrials.gov/ct/ show/NCT00028002?order=1.

The large EORTC 62024 trial continues to accrue patients. Many different centers are participating in this adjuvant Gleevec for GIST trial. Further information about this trial can be found at www.eortc.be/protoc/ Details.asp?Protocol=62024.

SARCOMA COLLABORATION SUMMIT

On Saturday, Nov. 19, several sarcoma patient advocacy organizations met for the first time to collaborate on a shared mission: to find a cure for sarcomas.

Representatives learned about each organization’s unique role, efforts and contributions; established a communication network between all groups; discussed the most current developments, issues and needs for advocates; and defined mutual goals and collaborative strategies.

At the end of the meeting, the group decided on a name — iSPAN, short for International Sarcoma Patient Advocate Network — and two task forces were established. One will address patient education, support and outreach, the other will undertake legislative lobbying. Each task force set up an action plan for the next six months.

The following organizations were represented: Amschwand Foundation, STS Patient Advocate Committee of Children’s Oncology Group, Desmoid Tumor Research Foundation, GIST Support International, Jennifer Hunter Yates Sarcoma Foundation, Karen Wyckoff Rein In Sarcoma Fund, Liddy Shriver Sarcoma Initiative, Life Raft Group, National Leiomyosarcoma Foundation, Sarcoma Alliance for Research through Collaboration, Sarcoma Alliance, and the Sarcoma Foundation of America.

The summit would not have taken place if not for the help of Sharon Anderson, whose dedication as a patient advocate made it possible.

RESEARCH TEAM MEETING

The Life Raft Group Research Team met Saturday, Nov. 19 for several hours prior to the start of the CTOS general session. Joining the LRG Research Team were several members of the Board of Directors. Dr. Jonathan Fletcher led the discussions. In a matter of a few hours, priority allocations were made for the components of projects that have been given priority over the past few months.

The LRG is working with a truly amazing group of researchers. There is an unprecedented environment of collaboration and cooperation. The process is moving forward with exceptional speed; the first grants will be awarded in early 2006. By capping the amount of funds that may be used for indirect costs at 10 percent, the Life Raft Group is ensuring that more money is available to researchers. In contrast, indirect administrative costs can consume 50 percent or more of the grants institutional researchers receive. This could well become a model for other organizations.