ASCO 2011: GIST Overview

June, 2011 -This year’s American Society of Clinical Oncology conference (ASCO), held in Chicago in June, produced a number of interesting and informative GIST-relevant presentations. Below is an overview and we will be posting the rest of the articles very soon.

Key findings

 Three years of adjuvant imatinib therapy improves overall survival.

 Imatinib levels drop significantly at three months of treatment.

 Regorafenib third line on track with improved survival. More survival data is now available for dasatinib, nilotinib, sorafenib and other third line options.

 GIST genotype based therapy is moving into the clinic.

Implications of longer term therapy

The overall survival benefit found in the 36 month adjuvant imatinib trial means that newly diagnosed GIST patients will likely be on therapy for at least three years and possibly much longer for high risk patients. The key to determining who is a candidate for adjuvant therapy is in using the patients primary tumor pathology report detailing tumor location, size, and mitotic index to determine the risk of recurrence. In the ReGISTRy database, the records of over 30 percent of patients on adjuvant treatment did not have a mitotic index; 10 percent did not have tumor size. Since adjuvant therapy can be a longer term commitment that can encroach on lifestyle, it is important for patients to have an accurate and detailed risk assessment using these key data from the original tumor pathology report.

Published results of the 36 month adjuvant trial also showed that patients with exon 11 mutations got an even greater benefit from longer adjuvant imatinib therapy. Mutational analysis now has the potential to help patients make the adjuvant treatment decision.

While risk analysis is now essential, there is still a question about which patients are most likely to have progress without adjuvant therapy. Formal investigation of biomarkers for risk of recurrence is now needed.

Managing long-term imatinib therapy also needs to be easier. There is a need for formal studies of side effects and compliance management for patients who are at increased risk of encountering problems in these areas. Compliance is even more of a survival issue now.

Read more about adjuvant therapy here.

Imatinib blood levels

The evidence continues to mount supporting a relationship between imatinib blood levels and progression. There is now also evidence that blood levels decline after approximately 90 days of therapy. There is a growing need for a standard imatinib blood level test and a growing need to incorporate blood level testing into standard practice especially for high risk patients and those experiencing debilitating side-effects.

Third line treatment options expanding and benefits better defined

Reports on five phase II trials in GIST provided new data about prospective and off-label third line options. Regorafenib looks to be on track as phase II data supports the ongoing phase III trial. Although preliminary, data on other phase II trials in sorafenib and dasatinib may help patients and oncologists make trial participation and off-label decisions for second line patients experiencing progression.

Genotype or subgroup-based therapy

A trial for PDGFRa D842V patients marks the advent of GIST subgroup based therapy. Newly diagnosed patients with stomach primaries have a small but significant chance of having this mutation. Mutation testing for all newly diagnosed patients can help five percent of patients avoid treatment with drugs that are known to have no effect on this mutation.

Treating subgroups of GIST patients based on mutation will mean smaller target populations for clinical trials and it will be necessary for more trial sites to recruit fewer patients from each site area.