ASCO 2020: First Comprehensive Assessment Highlights the Importance of Germline Analysis in Advanced-Cancer Patients

Dr.  Zsofia Stadler

Dr. Zsofia Stadler

During the American Society of Clinical Oncology (ASCO) Virtual Scientific Program, Memorial Sloan Kettering (MSK) Medical Oncologist Zsofia K. Stadler, MD, will present a study where she and her team sought to assess the clinical utility of germline mutation profiling for targeted therapeutic interventions in a pan-cancer patient population, or a population with similarities and differences among the genomic and cellular alterations found across their diverse tumor types. The research, which she will discuss on Saturday, May 30 at ET during the Cancer Prevention, Risk Reduction, and Genetics Session, demonstrates the first comprehensive assessment of the clinical utility of germline alterations for therapeutic actionability in a population of patients with advanced cancer.

Germline mutations, also called germline variants, are passed on from parents to offspring. This happens when a gene mutation in a parent’s reproductive cell (egg or sperm) becomes incorporated into the DNA of every cell in the body of the offspring.

Identification of germline alterations in cancer patients has many implications, including appropriate cancer surveillance options, potential risk-reducing measures, predictive genetic testing for at-risk relatives, and targeted therapeutic actionability.

The study utilized MSK-IMPACT™ (which stands for integrated mutation profiling of actionable cancer targets), a high throughput, targeted-DNA-sequencing panel for somatic mutations created by the Department of Pathology at MSK. All patients who had germline genetic testing through a prospective protocol via MSK-IMPACT™ were identified (N=11,974) from 2015-5/2019.

“In this analysis, 7.1 percent of patients harbored a targetable germline variant, which highlights the increasing importance of germline analysis in advanced cancer patients for selection of both FDA-approved treatments and clinical trial participation with germline-targeted therapeutics,” said Stadler. “Although, it is important to note that these numbers are not static. With the emergence of novel targeted treatments with new FDA indications, the therapeutic actionability of germline variants is likely to increase over time.”

In this population, 44 percent of these patients received the targeted drug, with >40 percent receiving the therapy in the research setting, which shows the significance of utilizing these drugs in clinical trial accrual and participation. Identification of cancer susceptibility syndromes also remains important for cancer surveillance and risk-reduction measures, and cascade genetic testing of at-risk family members. More information about the methods, results and, conclusions can be found in the abstract here.