Conflicted Confidence: Academic Oncologists' Views on Multiplex Pharmacogenomic Testing
Authors: Michael J. Hall
Journal: Journal of Clinical Oncology (2014)

Multiplex somatic genomic tests simultaneously evaluate multiple pharmacogenomic loci in the tumor genome to identify variants that may drive the growth, invasion, and/or metastatic spread of cancer and that may serve as targets for currently available or experimental therapies. In recent years, a growing number of multiplex somatic genomic panels with the capacity to examine tens to hundreds of genetic loci have become available to oncology care providers through research studies and commercial sources, in large part as a result of the improved time and cost efficiencies afforded by multiplex testing using next-generation sequencing technologies. A minority of the genomic loci that are sequenced by multiplex somatic genomic tests may harbor clinically relevant variants for which targeted therapies are available and approved by the US Food and Drug Administration for the particular indication (eg, anaplastic lymphoma kinase [ALK] inhibitors for patients with adenocarcinoma of the lung found to have an ALK mutation), whereas the remaining variants when detected may best be considered clinically experimental at this time. This latter group includes genes and genomic loci containing variants that are, first, potentially actionable, including those for which an approved targeted therapy exists but for which the indication is unproven and unapproved, and variants for which an experimental therapy exists but is unproven for the current indication, and second, other variants that are of uncertain significance, and thus neither clinically relevant nor potentially actionable at this time. Although genomic testing is widely endorsed, the clinical utility of routine multiplex somatic genomic testing remains unclear at present, both because of cost and insurance coverage concerns and because of the high potential of this testing to generate clinically uncertain information. With an abundance of new and powerful genomic tests entering the clinical arena, the oncologist has a critical responsibility to determine how best to integrate multiplex somatic genomic testing into clinical practice. Indeed, the National Genome Research Institute established the Division of Genomics and Society in 2012, in part to focus attention and resources on the societal impact of genomic advances. A growing body of literature has begun to examine genomic testing from the viewpoint of health care professionals faced with this daunting task. Studies by Fargher et al and, more recently, Haga et al have queried views of pharmacists, primary care providers, genetic counselors, and others regarding genomic and pharmacogenomic testing, and, although generally eliciting positive attitudes toward the value of genomic testing in health care, have identified highly diverse views of perceived roles in delivering genomics-based medical care and equally diverse (and often negative) assessments of perceived preparedness to do so. However, previous studies have not specifically examined clinically active, academic oncologists’ perceptions of the ways in which multiplex somatic genomic tests will affect the care of patients. In the article accompanying this editorial, Gray et al present the results of a survey of practicing oncologists at the Dana-Farber Cancer Institute (DFCI) that was conducted before the roll-out of a researchbased, center-wide multiplex somatic genomic test (OncoMap). Using mixed-methods survey techniques, the investigators offer a snapshot of how academic physicians from a leading National Cancer Institute–sponsored comprehensive cancer center perceive multiplex testing and the information it will generate, their intentions for its use, and to what degree these individuals express confidence in their abilities to incorporate multiplex testing into patient care. The investigators report findings that are timely and relevant to academic and community oncologists alike, and are particularly impressive for the robust response rate (61%) that was achieved from a nonincentivized, Web-based survey. Included in the 160-participant sample were medical oncologists (43%), surgical oncologists (29%), and radiation oncologists (19%), who as a whole reported a broad range of professional effort devoted to clinical practice, research, and administrative or teaching duties, as well as a broad diversity of research interests ranging from clinical trials to basic science. At baseline, exposure to somatic genomic testing for approved targeted therapies was modest. Surgical oncologists and radiation oncologists in particular reported a low use of somatic genomic testing in their practices—36% and 71%, respectively, had never ordered a routine genomic test (eg, such as KRAS testing to inform use of anti–epidermal growth factor receptor therapy in colorectal cancer treatment). In addition to describing participant interest in and intentions with respect to the OncoMap test, the investigators hypothesized that being a medical oncologist, high baseline use of somatic testing, and a third factor, termed genomic confidence, would be associated with greater interest in multiplex somatic genomic testing for patients and stronger intentions to disclose the results to patients. Genomic confidence was measured on a three-item scale devised for the current study that queried participants’ confidence in knowledge about genomics, ability to explain genomic concepts to patients, and ability to use genomic information to guide treatment. Finally, investigators additionally hypothesized that medical oncologists would be more likely to use multiplex genomic test results to inform cancer care. JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 32 NUMBER 13 MAY 1 2014