Editorial: The time for routine mutational testing has come

By Norman Scherzer

Reports continued at the American Society of Clinical Oncology (ASCO) meeting about various aspects of the relationship between mutational status and treatment efficacy. Heinrich et al. reported that Sunitinib (Sutent) response in Gleevec resistance GIST correlates with KIT and PDGFRA mutation status. Janeway et al. reported on wild-type pediatric GIST (i.e., no detectable mutation) responding to Sutent. Kleinbaum et al. reported on a familial GIST cluster with an exon 11 deletion. Blanke et al. reported on the long term follow-up of the first Gleevec trial for GIST, once again confirming that patients with an exon 11 mutation had the best responses. Other reporters noted that GIST tumors outside of the abdomen (prior reports have noted that exon 9 tumors are more likely to occur outside of the abdomen) contributed to a higher risk for recurrence.

These reports are but the latest in an accumulation of information about the relationship between mutational status and treatment efficacy.

What do we know now:

• Gleevec works best with exon 11
• Sutent works best with exon 9 and with wild-type kit (thus accounting for the Pediatric GIST response).
• Exon 9 mutations respond better to higher doses of Gleevec
• There is some suggestion that exon 11 mutations may respond to higher doses of Gleevec.

At ASCO Jerry Call and I spoke to a number of researchers and clinicians about routine mutational testing of GIST patients as part of their diagnosis. We could not find anyone who did not agree that this was a good idea. We submit that the time has come to move such mutational testing from occasional research to routine clinical management. That would accomplish two major results: First, it would give each clinician critical information needed to determine the choice of drugs and the dosage level of drugs for each GIST patient. Second, it would permit future researchers to have this information and to be able to incorporate it into their analysis of their clinical trial data. At this time each researcher has to repeat mutational testing for patients that were previously tested in an earlier trial.

The time for routine mutational testing has come.

Note: At the present time mutational testing can be performed by Oregon Health & Science University for a fee. Information about this process can be found on our website at http://www.liferaftgroup.org/treat_gleev _response.html