Friday, May 30 through Tuesday, June 3, 2008
Carolyn Grobe, Marina Symcox and Sherri Janousky attended ASCO this past weekend in Chicago at McCormack Place on Lake Michigan. On the massive exhibit floor, Big Pharma was pushing pens and coffee drinks; one company even provided a compass, undoubtedly to help us find our way back and forth to the educational sessions in the East or West buildings of this vast complex.
It seems just as challenging to present the huge amount of information presented at ASCO. To assist in this process, here is the list of GIST-related abstracts: http://www.abstract.asco.org/CatAbstView_55_80_AA.html
To search via author, title or abstract number, go to http://www.asco.org/ASCO/Abstracts+%26+Virtual+Meeting/Abstracts or to search categories by any word, try http://www.abstract.asco.org/ConfCatView_55.html
WIKI is a great tool; each of us can add our individual remarks and contributions following this fantastic five-day event. This may be an ongoing process for now as we decipher our notes and await the publication of the slides. Sherri is also unavailable for a few weeks due to business obligations and will share her observations later.
Marina met with Infinity Pharma executives RE: IPI-504 heat-shock protein inhibitor clinical trial. IPI504 is new concept for treating cancer with a new target Heat Shock 90...international phase III trial for GIST planned for later in 2008. Marina found the Infinity team very personable and had an enjoyable time visiting with them. She will be going to visit with them again next week when she has an appt at DF...to discuss how we can best educate patients on the internet about how their drug works, and their upcoming trial. See the Forbes article on this subject: http://www.forbes.com/2008/05/30/asco-cancer-infinity-biz-healthcare-cx_mh_0531infinity_print.html)
Four oral presentations on GIST today....this is quite a lot of ASCO podium "air time" for our disease. While some of the novel "flash" has waned for GIST compared to last time Marina attended in 2005, and Sherri's and Carolyn's attendance last year, we still get a lot of attention!
Preliminary data Phase II trial at UIC suggests Sorafenib is active and well-tolerated in patients with Gleevec and Sutent resistant GIST. http://www.abstract.asco.org/AbstView_55_31026.html
IPI-504 HSP 90 inhibitor has been well-tolerated overall and shows promising early evidence of activity in the treatment of pts with TKI-resistant GIST. http://www.abstract.asco.org/AbstView_55_33800.html
IGF Factor in GIST results reveal for the first time that the IGF1R gene is amplified and the protein is overexpressed in wild type and pediatric GISTs. The results demonstrate that the aberrant expression of IGF-1R may be associated with oncogenesis in a subset of GISTs that lack c-KIT or PDGFRα mutations and suggest an alternative or complementary therapeutic regimen in the clinical management of GIST, especially in tumors that respond less favorably to imatinib-based therapy. http://www.abstract.asco.org/AbstView_55_35078.html Marina had an enjoyable time chatting with author Andy Godwin-he is very personable...Keep him and Fox Chase in mind if you have wild type GIST--your samples could be helpful for his research.
Time dependence for GIST relapse Findings that a particular mutation in exon 11 KIT has a worse prognosis...deletion of residues 557 and 558. These patients have a greater chance of recurrence in the first four years...but not after four years. http://www.abstract.asco.org/AbstView_55_31503.html
Marina had a nice chat with David Epstein, CEO and President of Novartis at their booth. She is one of their very first GIST/Gleevec patients (year 2000), and so they were interested in meeting up with someone who has been on Gleevec successfully for almost 8 years.
Patient and Survivor Care poster sesions were presented Saturday afternoon covering many subjects. Cancer-related complications was an area of great interest with many patients now experiencing years of progression-free survival on cancer therapies. The abstract "Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate (Sutent)" concluded 15% of studied patients developed symptomatic Grade 3/4 heart failure. A history of congestive heart failure, coronary artery disease and lower body mass index were factors associated with greater risk. http://www.abstract.asco.org/AbstView_55_34016.html
With patients living longer, quality-of-life issues were presented as well under the Patient Care category, with a wide variety of issues, from pain management to qigong. Antidepressant effects of a yoga program in breast cancer patients (abs #9566) determined that yoga can be used for managing self-reported depressive problems. Abstract 9502 demonstrated positive effects of aerobic exercise on the physical performance and treatment-related symptoms during myeloablative chemotherapy.
It was recognized that nutritional deficiencies should be identified in lung cancer patients, even in those who are not losing weight (abs 9567). Specifically, Vitamin D is deficient (lack of sunlight and in diet) in the general population and especially in women with breast cancer (abs 9583). Abstract 20712 evaluated interactions between supplements and cancer drugs at the Block Integrative Cancer Center. "While patients seeking integrative cancer treatment have a high incidence of advanced cancers and often take large numbers of supplements, no patients included in this study were determined to be at risk for major herb-drug interactions likely to cause immediate serious clinical problems. Vitamins C and E, coenzyme Q10 and garlic were the most prevalent supplements taken." However, instances of potential problems requiring counseling were observed and it is recommended you inform your doctor of all herbs and vitamins you consume.
An evaluation of CAM at Cancer Treatment Center of American was reviewed in abstract 20656. In their integrative treatment setting, they observed a statistically significant improvement in several cancer-related symptoms affecting quality of life among patients during 3 months of treatment. In addition to receiving aggressive cancer-directed therapy, 294 patients underwent a comprehensive program of nutritional, spiritual, physical, naturopathic, and emotional support. They are now more closely examining the impact of specific integrative and supportive care regimens on the quality of life outcomes of their patients.
Abstract 9560 examined the needs and perceptions of spiritual care among advanced cancer patients, with the majority reporting multiple spiritual issues. These issues frequently surround meaning-making, seeking deeper existential connections, forgiveness, and existential questions or doubts. While most patients believe that spiritual needs should be addressed by oncology providers as part of their cancer care, most do not receive spiritual care. Abstract 9598 demonstrated that increasing spirituality, especially among patients with recurrent disease, may significantly improve feelings of hopefulness.
Sunday evening, Marina attended "CBCE presents Sarcomas as a paradigm for personalized medicine and targeted therapies" at Marriott Chicago Downtown Magnificent Mile - Dr. George Demetri, moderator.
Marina and Carolyn spoke with Dr. Judy Garber, principal Dana-Farber investigator of the FLAG Project (Families Learning about GIST). The project's goals are to: 1) look at which genes cause GIST to develop in families, 2) study the cancer risks in families with GIST, and 3) look at clues that may be related to hereditary GIST, such as non-cancerous skin growths. If you have a diagnosis of GIST, you are eligible to participate. Because this study's primary focus is you and your family's genome, you will be able to know or confirm which exon mutation you have. You can download FLAG study materials at https://projectflag.org/index.php?option=com_frontpage&Itemid=36
The Education Session we attended today was an overview of GIST research entitled "GIST comes of age -- current management using molecular pathology, surgery and targeted therapies." The information wasn't new but well correlated and presented by the distinguished team of Drs. George Demetri, Ron DeMatteo and Jean-Yves Blay.
Their presentations were respectively entitled "The impact of molecular biology in management of GIST - matching targeted therapies to genotypes", "Surgical management of GIST including imatinib-refractory disease" and "Controversy in the adjuvant treatment of GIST." As soon as we review the slides mid-week, we will report on these presentations.
Dr. Demetri stated that GIST has been the model for matching targeted therapy to genotype and we know 5 of 6 patients have a mutation of C-kit, either in exon 9, 11 (deletion), 11 (point mutation), 13, or no mutation, also called wild type (WT). Although WT also have activated C-kit mutations, there is no understanding of the mechanism of action for these mutations.
With Imatimib (IM), overall survival has tripled in patients with advanced metastatic GIST in both the North American and European/Australian studies cited. Many people have had a huge bulk reduction of their tumors, but some GIST tumors do not shrink while on targeted therapies but become hypodense.
When they first present, GIST patients usually have only one mutation. Most patients have an exon 11 kit mutation (76% of patients) which is sensitive to IM, exon 9 (8-10% of pts) appears to be dose sensitive to IM (800mg vs 400 mg). C-kit mutations on exon 13 may be sensitive to IM, but exon 17 is resistant. PDGRFA mutation on exon 12 (0.3% of pts) is sensitive and exon 18 (6% of pts) is resistant to IM.
Patients with similar exon mutations still present with a wide variety of genetic profiles confirming what we know... that gist is not one disease but a family of complex diseases. Pediatric GIST, in particular, may be a very different disease because of the lack of loss of genetic material that adult GIST exhibits. He suggests that maybe we should be defining all cases of GIST by the molecular tool rather than by expert eyes. Should be pick the dose or drug type on the basis of these molecular subtypes?
Demetri states gastroenterologists think GIST is a benign disorder. Micro-gists smaller than 5 mm have been found in 35% of 100 incidental consecutive gastrectomies (not cancer patients)in Japan; in Germany, gist under 1 cm were found in 22.5% of autopsies over the age of 50. Few of these GISTs are ever clinically relevant but they do possess kit mutations, indicating there is another signal of malignancy. This is an area that needs more research.
"Imatinib and its correlation with clinical response in patients with unresectable/metastatic GIST" revealed that exposure to adequate drug levels of Gleevec appears to correlate with clinical benefit and suggests the importance of monitoring exposure in the blood for optimal clinical outcome. Patients with the lowest Gleevec levels show the lowest overall objective response and shortest time to progression. http://www.abstract.asco.org/AbstView_55_35036.html