Genetic tests guide cancer therapy, improve efficacy

Individualized cancer therapy adopts the idea that each patient and their cancer have unique traits, including how a drug will be handled in the individual’s body and whether it will be effective against the individual’s cancer. 

Cancer treatment has continued to shift from traditional cytotoxic therapies, aimed at inhibiting the growth of fast-growing cells, toward targeting a particular cellular pathway that appears to be activated in a patient’s particular cancer, according to Christine M. Walko, PharmD, FCCP, BCOP, of the Moffitt Cancer Center. 

Walko, who is a personalized medicine specialist at the DeBartolo Family Personalized Medicine Institute, Division of Population Science, at the Center, will go into depth on this topic at the session, “The Role of Pharmacogenomics in the Era of Precision Medicine,” at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting in Chicago, on Friday, June 3, at 2:45 p.m.

She will talk about opportunities and challenges of using somatic (tumor) genetics to guide targeted-therapies and immunotherapies. She will also discuss determining whether a genetic mutation is clinically actionable, intrinsic/acquired resistance mutations, and serial genetic testing using liquid biopsies to direct targeted therapy. In addition, she will discuss assessing mutation burden to direct immunotherapy, which will be explored in greater detail in the research abstracts at ASCO.

Genetics in action

There are numerous examples of the use of genetics to guide treatment in cancer, according to Walko.

Walko

“We commonly assess BRAF status in melanoma, KRAS status in colon cancer, EGFR [epidermal growth factor receptor] and others in lung cancer, etc.,” she explains. “Additionally, lung cancer patients with an activating EGFR mutation who receive erlotinib may respond for about 10 months, but then can develop resistance mutations such as EGFR T790M that require a change in therapy to a drug to overcome the resistance such as osimertinib.”

Additionally, the number of mutations can predict for higher responses to immunotherapy, she says.

Finding accurate biomarkers to help direct cancer treatment is imperative, says Walko. “These agents are expensive themselves and the cost of toxicities can also be expensive,” she says. “Thus, if we can identify the patients most likely to respond to a certain therapy, we can use these expensive medications in a cost-effective manner while sparing patients less likely to respond from the costly toxicities.”

Next: Genetics optimize efficacy

The use of genetic testing to guide cancer therapy helps optimize efficacy by identifying patients who will likely respond well to a therapy, and by directing patients who are unlikely to respond well to more effective treatments, while avoiding costly side effects.

“We need to continue to identify and validate accurate biomarkers to continue to optimize this process,” Walko says. “Ongoing research effects, such as basket trials and targeted therapy registry trials will help to further identify actionable mutations and support matched targeted therapies to help further the treatment of all cancers.”

Walko reiterated that while there are benefits of pharmacogenomics-more effective and cost-effective treatment options-the challenges are numerous.

“This includes optimizing assays, defining clinical actionability, expanding experience with liquid biopsies using cell-free DNA from plasma, the need for development of bioinformatics methods to share large amounts of data across cancer centers, etc.,” she says.