Dr. Salani on the Role of Molecular Profiling in Endometrial Cancer Treatment

Ritu Salani, MD, MBA, director, Division of Gynecologic Oncology, professor, Obstetrics and Gynecology, University of California, Los Angeles, Jonsson Comprehensive Cancer Center, discusses the importance of histological subtyping and molecular profiling in developing treatment strategies and improving outcomes for patients with endometrial cancer.

With recent developments in personalized medicine, performing tumor profiling in patients who may require adjuvant therapy will likely become a new standard practice, Salani states. Despite this shift, is important to note that patients with early-stage, low-risk disease may not need this approach.

Clinicians may look to eliminate and de-escalate therapy in patients with POLE mutations, as they generally have a more favorable prognosis than other disease subtypes in advanced stages, Salani continues. If this mutation is not present, evaluating patients’ mismatch repair status can identify individuals that will respond more favorably to checkpoint inhibitors, even in the frontline setting. Single-agent checkpoint inhibitors such as dostarlimab-gxly (Jemperli) and pembrolizumab (Keytruda) are already effective options in the second line, but their potential use as frontline treatments has yet to be fully explored.

Patients could also express a mutation in the p53 gene, indicating the need for chemotherapy due to the generally poor prognosis associated with this profile. Looking at other potential targeted strategies may help clinicians optimize patients’ outcomes, but it is important to note any toxicities, Salani emphasizes.

Lastly, identifying individuals with a nonspecific molecular profile pattern can alert clinicians to the need for less targeted options when creating a treatment approach, as they don’t have molecular targets, Salani concludes.