A look back at 2007, a look ahead at what is to come in 2008
By Norman Scherzer
LRG Executive Director
The advent of the New Year is a wonderful opportunity to take stock of what the Life Raft Group has accomplished in 2007, as well as reflect on what has already begun and what we still hope to achieve. It is hard still to list the triumphs and defeats of the last year in this article, when the ultimate defea
A Look Back
We expanded the content and the scope of our informational and educational efforts. Once again, we have raised the bar for scientific content in our monthly newsletters and struggled to maintain a balance between covering coping issues and heroic stories of our members and providing the scientific material that researchers, clinicians and a growing number of patients and caregivers have come to depend upon to keep them informed. We also created new educational materials, including a cutting-edge pamphlet on “Navigating GIST Clinical Trials” and built a new and sophisticated system for tracking these clinical trials. We began a series of monthly webcasts featuring experts in clinical care, research and education and archived them in a new onsite webcast library.
We continued to expand the content of our websites and have almost completed our first total redesign and reorganization of the LRG website. We are planning to launch this in a few weeks.
On an ongoing basis, we have counseled patients one-on-one about their options for choosing and accessing treatment and we intervened, on numerous occasions, behind the scenes to overcome obstacles to obtaining life-saving drugs. Our advocacy efforts continued, confronting cutbacks in Medicare and insurance coverage for GIST patient treatment.
As an ongoing special mission we once again tried to bring quality care and coordinated research to the treatment of pediatric GIST patients. We cosponsored, with the National Institutes pediatric GIST medical professionals and patients which has culminated in an agreement with the NIH to host a clinic for pediatric GIST patients starting this coming spring. We will have a lot more to say about this in the near future but suffice it to say that this is a most exciting development to improve the care of our young patients.
On the research front we are a few months away from completing the first two years of our five-year strategic plan to discover and overcome the reasons that GIST patients develop resistance to treatment. To date we have awarded nearly two million dollars to implement this plan, created by our research team. This effort is coordinated by Dr. Jonathan Fletcher at Dana-Farber/Brigham & Women’s Hospital and his colleagues: Drs. Cristina Antonescu and Peter Besmer of Memorial Sloan-Kettering Cancer Center, Drs. Chris Corless and Mike Heinrich of Oregon Health & Science University, Dr. Maria Debiec- Rychter of Catholic University in Leuven, Belgium, Dr. Brian Rubin of the Cleveland Clinic and Dr. Matt van de Rijn of Stanford University.
Our research is unique in many ways, including being based upon a coordinated plan of action, a novel grants process that caps indirect costs at 10 percent (instead of typical 60% to 75% rates), and a philosophy that mandates cooperation, collaboration and accountability in place of isolation and competition. In addition, we have created two tissue banks, for adult GIST at Stanford University and Pediatric GIST at Memorial Sloan Kettering.
As a complement to this research strategy we vastly expanded our GIST patient registry by converting our extensive medical information to a dramatically more robust and comprehensive data base format. In the very near future we will be publishing our latest forwardlooking analysis of the relationship between Gleevec dosage and survival.
A Look Ahead At Issues Affecting Survival
The core mission of the LRG is survival and it is not yet met. Despite early and dramatic responses to Gleevec in excess of 85 percent, the specter of resistance and an endless roll call of deaths call for a sober assessment of the obstacles that remain to be overcome.
It is simply not enough to recount our many successful projects, virtuous though they may be. GIST patients, like most cancer patients, too frequently pass into the night and do so with a graceful courage marked by a soft silence. We have much to do to achieve our mission.
Our blueprint for ensuring the survival of GIST patients builds upon using existent knowledge as well as further research.
Our research has begun to make progress in identifying the downstream pathways that characterize Gleevec resistance and in finding ways to shut these down. We believe that our strategic planning and coordinated approach to research will provide a pathway to an eventual cure. Our initial objective is to turn GIST into a chronic disease, probably by providing the patient with a cocktail mix of drugs that ensure survival and a high quality of life. The ultimate objective is to find a cure by totally destroying every GIST cancer cell so that the patient will be able to stop taking drugs, avoiding high expenses and inevitable side effects. We will shortly begin our third year of our five-year plan.
Although research must remain the cornerstone of achieving our mission there is much that can be done with what we currently know to improve the chances of survival.
Prescribing the right Gleevec dosage for metastatic GIST patients: The current consensus is to treat metastatic GIST patients with 400mg per day and to cross over to a higher dosage should progression occur. However, it is not at all clear to us that this consensus is always correct. We now know that patients with an exon 9 mutation respond dramatically better to a higher dosage of Gleevec and do rather poorly on a 400mg dosage. For patients with surgical tissue on file it would seem prudent, if not urgent, that the tissue be tested for genetic mutation and that exon 9 patients be given a higher dose. The situation for other patients, generally those with exon 11 mutations, is less clear and will be the subject of a Life Raft Group study to be released next month.
In addition to routine mutational testing to determine the existence of exon 9 mutations we suggest that routine plasma testing be introduced to attempt to determine the level of Gleevec in the body. There is evidence to suggest that the clearance levels of Gleevec increase over time and some reasonable speculation that this may mean that a starting dosage of 400mg of Gleevec is not sufficient for all patients over time.
Given the efficacy of current treatment options once Gleevec resistance has developed we would submit that currently it may be easier to prevent resistance from developing than trying to reverse it once it occurs.
Adjuvant treatment following surgery for a primary tumor: Although we have data only from one early clinical trial, that data suggests that patients given preventive (adjuvant) treatment, following the successful removal of a primary tumor (i.e. with clear margins), have a lower rate of recurrence, at least in the short term.
Early diagnosis: We have known for some time that the prognosis for patients with smaller tumors and with lower mitotic rates. It would seem reasonable that the earlier the patient is diagnosed the more likely the tumor would be smaller. Little attention has been paid thus far, to finding ways to promote earlier diagnoses of GIST. A focus of the Life Raft Group’s efforts in the coming year will be to provide those doctors most likely to encounter the earliest symptoms of GIST, including family practitioners, internists, gastroenterologists and emergency room physicians, with information designed to raise their index of suspicion.
Accessing Treatment: The cruelest situation for GIST patients is the inability to access available treatments. The two major issues are a lack of knowledge about current treatments, including those in clinical trials, and a combination of logistical and financial obstacles preventing access. As more drugs are approved for the treatment of GIST the likelihood is that more patients will be seen by more inexperienced oncologists, particularly in health settings like the United States. That reality, combined with a complex number of clinical trials, means that there is an educational need to reach both physicians and patients with the latest treatment and clinical trial information. Making sure that nobody dies because of ignorance, either their own or that of their physician, is the driving force behind the Life Raft Group’s educational programs.
The hard reality of logistics and finances often enter the scene after a particular treatment is identified. Gleevec and Sutent, the current Food and Drug Administration-approved drugs for GIST, are expensive. Although both Novartis (maker of Gleevec) and Pfizer (maker of Sutent) have patient assistance programs, they vary widely in different countries and have financial eligibility cutoffs. Forty-seven million Americans live without health insurance and not all qualify for financial assistance for cancer treatment. Accessing clinical trials poses all sorts of obstacles, depending on where they are located (many are in expensive urban areas) and what they require in terms of travel and lodging. Few trials offer assistance for travel and lodging and many United States trial locations have prohibitive financial requirements for international patients. Accessing treatments through compassionate- use poses yet another set of difficulties and even the best intentioned pharmaceutical companies are no match for the onerous processes required by medical institutions for approving such drug use. Addressing these varied and many issues is a major priority for the Life Raft Group.
Quality Controls: Mistakes are an unfortunate reality in medical care. With relatively new areas such as the rapidly developing diagnosis and treatment of GIST, the lack of quality controls can be particularly problematic. For example, there is currently no reference laboratory for the complex mutational tests GIST patients need. There is no Board Certification for GIST specialists or even the broader area of sarcomas, the family of cancers to which GIST belongs. There is no reference testing for radiologists, including those who rarely see GIST tumors. The Life Raft Group intends to begin addressing quality control issues this year.
Much remains to be done on our pathway to a cure for GIST. The memory of those who have left us sustains us and the urgency of those struggling for survival drives us. I will pose this question once more: If not us, then whom?