An Interesting Trial

NCI is proposing to do a randomized trial with selected cancer patients based upon genetic profiling of the specific cancers. Namely they state:

Patients with melanoma whose tumors have mutations in the V600E region of the BRAF gene should have received and progressed on a specific BRAF inhibitor therapy to be eligible for NCI’s M-PACT trial.

Patients with lung cancer should have had their tumors tested for the presence of EGFR and ALK gene mutations, and, if mutations were detected, they should have received and progressed on therapies targeting EGFR or ALK, respectively.

 The specifically state:

Patients with all types of solid tumors will be considered for trial eligibility. For the randomization, patients will be assigned to Arm A (they will receive a treatment regimen prospectively identified to target their specific mutation or relevant pathway) or Arm B (they will receive a treatment regimen not prospectively identified to target their specific mutation or relevant pathway).  Patients in Arm B will have the option to cross over to Arm A to receive therapy identified to target their specific mutation or relevant pathway if their disease progresses on their initial study treatment.  As of January 2014, the study is open for patient accrual.  

What is interesting is that this appears to be a great beginning to such a procedure. One of the concerns, however, is that with BRAF V600 we seem MEK mutations following and then we must treat that one. The challenge is to try to better understand the evolving mutations that result as the tumors proliferate and spread. Thus we may then better understand how to treat the patient progressively and even perhaps prevent subsequent mutations. But this is well worth the following.

However there is the question of epigenetic factors which should be considered as well. Methylation is a prime factor which we know plays a significant part in many cancers, such as prostate and others. Other epigenetic factors such as miRNA and lncRNA are also considered of import. Thus focusing on genes is but one step.

Therefore it would be of interest to further consider:

1. Progression of genetic changes by time and location.

2. Complexities and proliferation of epigenetic changes as well as benign somatic epigenetic factors.

3. Family genetic analysis could also be of help to determined any heritability predilection.