Genetic testing is a rapidly growing area in which technology can outpace the understanding of its appropriate use. In the area of tumor genetics, this is especially true. An increasing number of cancer therapies are being developed and approved, many of which target specific genetic information contained in tumor cells. However, a lack of clarity exists among clinicians as to when gene sequencing should be ordered, what type of assays should be performed, and how to interpret the results.

In response, the American Society of Clinical Oncology (ASCO) has released a provisional clinical opinion to guide clinicians on the use of such testing.^[1]Chakravarty D, Johnson A, Sklar J, et al. Somatic genomic testing in patients with metastatic or advanced cancer: ASCO provisional clinical opinion. J Clin Oncol. 2022:Jco2102767. The recommendations are specific to solid tumors in patients with known metastatic or advanced disease and are limited to those tumor types in which identification of a genetic abnormality in the tumor cells would assist in guiding treatment decisions. They are not intended to address the use of genetic testing for diagnostic or prognostic purposes.

The authors provide a snapshot of agents approved by the FDA as of June 2021 and the genetic alterations they are designed to target. A key recommendation is that genomic sequencing be limited to tumors for which an approved therapy exists, or when contraindications to a therapy under consideration are linked to specific genomic markers. Another recommendation is that testing be performed in appropriately certified laboratories. The authors point to variation across laboratories in how assays are performed and reported, adding to the challenges of interpreting the information.

In addition to the complexity of interpreting genomic sequencing data, there are gaps in the understanding of how this translates into effective treatment. Simply knowing that a particular therapy targets a specific genetic sequence does not guarantee that the therapy will be effective. The authors emphasize the need for evidence-based clinical decision making and acknowledge that existing evidence is limited, as is our understanding of the impact of genetic alterations on protein expression or function.

While this publication provides useful guidance for clinicians, it is important to note that it an opinion based on informal consensus, and not an evidence-based guideline. Carelon recognizes the need for both high-quality evidence and clinical expertise in driving appropriate care. The Carelon genetic testing program is built on a solid foundation incorporating these essential components.

Dr. Michael Fisch, director of medical oncology at Carelon and a practicing oncologist at MD Anderson Cancer Center in Houston, TX, provided additional commentary on this issue. According to Dr. Fisch, “While this provisional clinical opinion recommends genomic testing in cases where genomic biomarker-linked therapies have been approved by the FDA, it also highlights important challenges that must be overcome in order to achieve clinically meaningful results. The next steps to improving care for members with advanced cancer should involve further study of the utility of specific strategies and implementation science to improve care delivery in this complex and dynamic realm of care.”

A major challenge in precision oncology is determining whether a specific genomic alteration in a potentially targetable gene is a passenger, actionable driver, or non-actionable driver. Not all alterations (variants, copy-number changes, or fusions) in actionable genes confer sensitivity to available drugs.

Chakravarty D, Johnson A, Sklar J, et al. Somatic genomic testing in patients with metastatic or advanced cancer: ASCO provisional clinical opinion. J Clin Oncol. 2022:Jco2102767.