No: A variety of technologic, clinical, financial, and logistic factors must be addressed first.
Genomic analysis could help meet the great need for better treatments for our patients with gastrointestinal cancers. But we are not ready for routine molecular profiling of tumors.
There are many assay platform limitations, such as variability in sensitivity and specificity, lack of rigorous analytic validation of some, and questions about selection of the genes on a platform. And tumors are heterogeneous and complex. Depending on where you biopsy from a particular lump and whether it’s a metastasis or primary, the gene expression profile may be very different. Also, gastrointestinal tumors commonly have multiple mutations that might be viewed as drivers.
We simply don’t know the drivers from the bystanders, and we don’t have the evidence linking drugs to these drivers. The best level of evidence is an FDA-approved drug-target interaction or dyad. But we don’t yet have that in most of the cases we face. Progress has been so slow in developing biomarkers because historically, they have been poorly valued.
Susan London/Frontline Medical News
Dr. Neal J. Meropol
Investigational drugs are not widely available. Clinical trial sites are often limited, and patients have to travel to them. Activation of studies with low expected accrual because they accept only very rare molecularly defined subsets of patients is costly, and getting compassionate access to a new drug in development is logistically complicated.
It isn’t practical to screen many patients to perhaps help a few when the evidence is simply not there; in a recent phase I trial, only 2% of 1,283 patients studied had a mutation identified, were matched to a treatment, and had an antitumor response (Clin. Cancer Research 2012;18:6373-83). At this time, genomic analysis requires fresh biopsies, so we are subjecting patients to extra biopsies, and there is a delay in decision making of weeks to months. Also, this requires a large infrastructure involving pathologists, informatics support, clinical geneticists, and bioethicists.
There is no mechanism to pay for drugs for off-label use. Payers are increasingly scrutinizing such use of expensive targeted agents, and costs are falling on our patients. Recommending cancer drugs with high coinsurance, high copays may simply not be ethical without strong evidence of benefit.
Cancer drug approval today is typically based on organ of origin and not genomics. The old paradigm that we are living with is histology based and requires large phase III trials to provide the level of evidence that will lead to a licensing approval. We are pressured to embrace an emerging paradigm when we make genome-based decisions using small studies looking for big effect sizes and accepting registry data.
We really don’t have a standard statistical approach to interpreting our current evidence; for example, what is enough evidence to lead us to conclude that a particular mutation should receive a particular therapy? And finally, there can be many unintended negative consequences of routine genomic analysis for our patients. We don’t want to give them false hope or subject them to the risks of needless biopsies and the financial burden of therapies that are not destined to help them. And we need to be prepared to address all mutations identified in the proper ethical fashion.
Dr. Neal J. Meropol is division chief, hematology and oncology, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland; associate director for clinical research, Case Comprehensive Cancer Center and associate director for clinical programs, University Hospitals Seidman Cancer Center; and the Dr. Lester E. Coleman Jr. Endowed Chair in Cancer Research and Therapeutics at Case Western Reserve University. Dr. Meropol disclosed that he has a consulting or advisory role with BioMotiv and has a relevant patent (Methods of Therapy for Cancers Characterized by Overexpression of HER2 Receptor Protein).