Preliminary news from ASCO
With over 3,000 physicians at ASCO this year and numerous presentations and educational tracks occurring at the same time makes it hard to attend each one. In addition, there were almost 60 different posters, abstracts or presentations about GIST. We won’t be able to cover them all, but interested readers can view all of the abstracts by searching for GIST here. The abstracts are free to view. Unfortunately, you have to pay to view most of the presentations; but if you can afford it and are interested, Virtual Meeting is really a great way to see the latest GIST research.
New Immunotherapy Drugs PD-1 and PD-L1 Inhibitors:
Michael Josephy posted last week about new immunotherapy drugs (PD-1 and PD-L1 inhibitors). These drugs may mark the beginning of the biggest cancer treatment paradigm shift since Gleevec and targeted immunotherapy. We believe that immunotherapy may finally be a reality in cancer treatment. Stay tuned for more in-depth details about these immunotherapy drugs in a future article.
Ponatinib In-Vitro Test Data:
The poster, presented by LRG research team member Michael Heinrich, presents in-vitro test data on ponatinib. Ponatinib (Brand name is Inclusig) is approved for use in patients with resistant forms of chronic myelogenous leukemia (cml). In cml, it is considered a third generation tyrosine kinase inhibitor (TKI). Lab date suggests that it is a very potent KIT inhibitor with wide spread activity against secondary mutations, especially those involving the activation loop (exon 17 in KIT). Activation loop mutations remain difficult to treat, although regorafenib (Stivarga) has activity against many of these mutations. The authors concluded: “PO (ponatinib) potently inhibits the majority of clinically relevant KIT mutant kinases and has a broader spectrum of activity compared to IM (imatinib), SU (sunitinib), or RE (regorafenib). Based on these data, a phase 2 study of PO in drug-resistant GIST is being initiated.” Secondary mutations are the most common cause of resistance for GIST patients with KIT or PDGFRA mutations.
The phase II trial will be starting for GIST patients in early June. The trial will initially open at the Knight Cancer Center in Portland Oregon (Dr. Michael Heinrich) with additional sites opening later at Fox Chase Cancer Center (Dr. Margaret von Mehren) and Dana-Farber Cancer Center (Dr. George Demetri). This trial is listed on clinicaltrials.gov and the LRG clinical trials database.
George Demetri (Dana-Farber) and Nikolas von Bubnoff (Freiburg University Hospital, Germany) presented extremely interesting data on the ability to detect DNA from tumors in the blood of GIST patients. Using different technology, the groups led by these two researchers showed that a recurrence of GIST is correlated with mutant free circulating tumor DNA (fc)DNA and that secondary mutations can be detected in fcDNA.
This technology could have important implications in two areas for GIST patients.
- Rising mutant fcDNA levels could predict a recurrence earlier than a CT scan. This could allow adjuvant patients to resume Gleevec at the earliest time point of a recurrence, potentially before a tumor could grow large enough to be seen on a CT scan. Adjuvant treatment studies suggest that treating GIST as early as possible may be more effective than waiting to a later time point (this is still a debatable point). Using this technology might allow a patient to “cycle” on or off Gleevec as needed according to rising or negative fcDNA levels. If proven effective enough, this technology might even be able to reduce the scan frequency of patients (reducing radiation and contrast-related negative effects on the kidney).
- fcDNA appears to be superior to traditional biopsies at detecting secondary mutations that cause resistance to Gleevec. Up until now, treatment decisions cannot be based on secondary mutations because a biopsy may only detect one or two secondary mutations when 10 or more could exist in a resistant patient. This technology gives a much more complete picture of secondary mutations. This could eventually allow treatment to be custom tailored to each patient based on the actual secondary mutations present.
Read more about George Demetri’s work on circulating tumor DNA using BEAMing technology here
Dr. von Bubnoff’s poster described preliminary results of a phase IIIb clinical trial (NCT01462994). Von Bubnoff’s team collected 291 plasma samples from 38 GIST patients with known mutations in KIT or PDGFRA. In contrast to the BEAMing technology used by Dr. Demetri’s team, von Bubnoff used a different method, allele-specific ligation PCR to detect fcDNA.
Patients with active GIST disease had significantly higher amounts of mutant fcDNA compared to patients with no evidence of disease and the amount of mutant fcDNA correlated with disease course. A positive test result or an increase in mutant fcDNA was seen in 5 patients with progressive disease or relapse. In contrast, a decline of tumor fcDNA was seen in 5 patients responding to treatment. Von Bubnoff’s conclusions were: “Our results indicate that free circulating DNA harbouring tumor specific mutations in the plasma of patients with GIST can be used as tumor-specific biomarker. The detection of resistance mutations in plasma samples might allow earlier treatment changes and obviates the need for repeated tumor biopsies.”
Read the von Bubnoff abstract here: http://meetinglibrary.asco.org/content/109224-132
The Affordable Care Act (ACA) and State Health Exchanges:
A number of breakout sessions were conducted regarding the impending state health exchanges/marketplaces that will be offered in an effort to cover those currently without health insurance. As of May 28, 2013, 17 states have decided to run the exchanges themselves, 27 will have the federal government run them on their behalf, and 7 will participate in a state and federal partnership (these totals include all 50 states plus the District of Columbia, meaning that all will participate in the exchange in some fashion). To see what your individual state is doing, please check http://kff.org/health-reform/state-indicator/health-insurance-exchanges/. Note that these totals reflect what the individual states are planning to do at this time, and this may change prior to the plans going live. States will begin sending out marketing materials and enrolling new patients on October 1st of this year, and to roll out the new plans on January 1, 2014. States will be using tiered plans named after precious metals (Bronze, Silver, Gold, Platinum), and individual states are not required to offer plans from every tier.
At this point, there are a number of questions still to be unanswered about these plans, including what drugs and procedures will be covered, and to what extent (i.e. co-pays or co-insurance levels), as states are not required to release this information until they begin enrolling. Also not yet decided is whether participants in these plans are eligible for patient assistance programs provided by pharmaceutical companies, and how cross-border care (subscribers who live very close to the border of another state) will be handled. As more information becomes available, we will be sure to report on it.
Stay Tuned To Learn More About ASCO in an Upcoming Article.