US Approval: Imfinzi with Chemo for Advanced/Recurrent Mismatch Repair Deficient Endometrial Cancer

AstraZeneca’s Imfinzi has been approved by the US FDA as a treatment for adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR). This decision was informed by the DUO-E Phase III trial, which demonstrated that Imfinzi, in combination with carboplatin and paclitaxel followed by Imfinzi monotherapy, significantly reduced the risk of disease progression or death by 58% compared to chemotherapy alone. The findings were published in the Journal of Clinical Oncology.

Endometrial cancer is the fourth most common cancer among women in the US, with over 66,000 new cases and nearly 12,000 deaths in 2022. While early-stage diagnoses have a high five-year survival rate of 80-90%, advanced stages have a survival rate of less than 20%, highlighting the need for new treatments.

Shannon N. Westin, Professor of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center, and the principal investigator of the trial, emphasized the significance of this approval: “With the incidence and mortality of endometrial cancer expected to increase, it is critical that we introduce new treatment options as early as possible in patient care. This approval indicates that durvalumab plus chemotherapy, followed by durvalumab monotherapy, delivers substantial clinical benefits for patients with dMMR endometrial cancer.”

Dave Fredrickson, Executive Vice President of the Oncology Business Unit at AstraZeneca, noted the importance of continuous innovation in this area: “There have been limited advancements in endometrial cancer treatment over several decades. As the burden of this cancer is anticipated to grow, immunotherapy combined with chemotherapy is becoming a new standard of care. The approval of Imfinzi presents a valuable new option for patients with mismatch repair deficient disease.”

The safety and tolerability of the Imfinzi and chemotherapy regimen were generally manageable and consistent with prior clinical trials, with no new safety concerns reported. Moreover, the trial also assessed another arm involving Imfinzi plus chemotherapy followed by Imfinzi combined with Lynparza (olaparib) as maintenance therapy, which also met the primary endpoint of progression-free survival (PFS). Overall survival (OS) continues to be assessed as a secondary endpoint for both treatment arms.

Endometrial cancer primarily affects women post-menopause, with most diagnoses occurring in women over the age of 60. It is the sixth most common cancer among women globally, and its incidence and mortality rates are expected to rise significantly by 2050. While early-stage disease is often treated with surgery and/or radiation, advanced stages require more effective treatment options. Immunotherapy combined with chemotherapy has emerged as a promising new standard, particularly for the 20-30% of patients with dMMR disease. However, there remains an urgent need for treatments for the 70-80% of patients with proficient mismatch repair (pMMR) disease.

The DUO-E trial, which included 699 patients with newly diagnosed advanced or recurrent endometrial carcinoma, evaluated the efficacy of Imfinzi combined with platinum-based chemotherapy followed by either Imfinzi monotherapy or Imfinzi plus Lynparza as maintenance therapy. The primary endpoint was PFS, with OS, safety, and tolerability as key secondary endpoints. The trial was conducted across 253 locations in 22 countries.

Imfinzi, a human monoclonal antibody that targets the PD-L1 protein, is part of AstraZeneca’s extensive immuno-oncology (IO) portfolio. This portfolio aims to harness the body’s immune system to combat cancer, and Imfinzi is currently approved for various cancer types worldwide. AstraZeneca continues to explore new IO therapies and combinations to transform cancer treatment and improve patient outcomes.