Upending Endometrial Cancer

Two-thirds of women diagnosed with endometrial cancer have localized disease and a 5-year relative survival of 95%. In contrast, 9% of women have metastatic disease at diagnosis and fewer than 20% survive 5 years after diagnosis. Immune and molecularly targeted therapies have improved outcomes for women with metastatic endometrial cancer. In a live virtual symposium at the 2021 ASHP Midyear Clinical Meeting, 2 experts linked genetic and biomarker testing in determining treatment options for patients with endometrial cancer in a presentation titled Caring for Patients With Endometrial Cancer Through the Management of Immune-Mediated Endocrinopathies and Adverse Effects of Targeted Therapy.

Sarah Hayward, PharmD, BCOP, began by highlighting the important role for genetic and biomarker testing for microsatellite instability high (MSI-H), deficient mismatch repair (dMMR), programmed death-ligand 1 (PD-L1), tumor mutational burden high (TMB-H), and human epidermal growth factor receptor 2 (HER2) in women with endometrial cancer. First, she explained that carboplatin and paclitaxel remain the gold standard for adjuvant treatment of uterine-confined endometrial cancer and for recurrent, metastatic, or high-risk disease. Dr Hayward differentiated the use of immune checkpoint inhibitors (ICIs) in the second-line setting by illustrating avelumab, dostarlimab, and nivolumab are included in the National Comprehensive Cancer Network (NCCN) guidelines as other recommended regimens for second-line treatment of recurrent or metastatic dMMR/MSI-H endometrial cancer. Lenvatinib combined with pembrolizumab is a preferred regimen for tumors that are non–MSI-H/dMMR, emphasized Dr Hayward, whereas pembrolizumab monotherapy is a preferred regimen in the NCCN guidelines for TMB-H and MSI-H/dMMR expressing tumors. She also noted that while neither agent has been approved by the FDA in endometrial cancer, bevacizumab may be used for patients who have progressed on prior cytotoxic chemotherapy and trastuzumab may be used for patients with HER2-positive, stage III/IV endometrial cancer in combination with carboplatin and paclitaxel.

Renee K. McAlister, PharmD, BCOP, began the second half of the presentation by illustrating how immune-related adverse events (irAEs) may affect any organ in the body and may present at any time during treatment. Dr McAlister highlighted strategies to manage irAEs, with a focus on endocrine toxicities, such as diabetes and hypophysitis. In general, patients with a grade 1 irAE are managed with close monitoring while continuing therapy; however, ICI therapy is held and corticosteroids are initiated for patients with grade 2 to 4 irAEs. She wrapped up the session with specific strategies for managing targeted therapy adverse effects and emphasized the role of the pharmacist in patient care.

Sarah Hayward, PharmD, BCOP, highlighted that “At present, ICIs and targeted therapies are only approved for use in the recurrent setting; however, clinical trials are evaluating use of ICIs in the frontline setting for endometrial cancer.”

Renee K. McAlister, PharmD, BCOP, differentiated endocrine irAEs by noting, “Typically patients do not require high-dose steroids or cessation of ICIs, though brief periods of high-dose steroids and holding ICI doses may be required for grade 3 or 4 acute toxicities.”