Advancing Endometrial Cancer Treatment with Targeted Therapies
Endometrial cancer is the sixth most common cancer in women and the most common of the female reproductive organs. It affects mainly post-menopausal women, and its incidence is rising, with over 400,000 new cases per year worldwide. As these diagnoses increase by 1-3% each year, there’s an unmet need for new first-line treatments for the nearly 80% of patients with advanced recurring disease who are mismatch repair proficient (pMMR), in which there is a normal expression of mismatch repair (MMR) proteins.
A recent breakthrough in first-line treatment for endometrial cancer is the use of immunotherapy in combination with chemotherapy as a first-line treatment in patients with primary advanced or recurrent endometrial cancer.
In June, the FDA approved the use of Durvalumab with carboplatin plus paclitaxel followed by single-agent durvalumab for patients with primary advanced or recurrent endometrial cancer. Moffitt is now ready to treat patients who qualify for the combination of immunotherapy and chemotherapy.
Dr. Hye Sook Chon, a gynecologic oncologist at Moffitt Cancer Center, was one of the trial’s many investigators and authors, exploring the benefits of immunotherapy on Moffitt endometrial cancer patients.
The Breakthrough: Olaparib and Durvalumab Plus Chemotherapy
The DUO-E Phase III trial, published in October 2023, studied the results of adding Durvalumab, a type of immunotherapy, to chemotherapy treatment, followed by maintenance with or without adding Olaparib, a PARP inhibitor.
The trial found strong evidence of the benefits of adding Durvalumab to chemotherapy for patients with mismatch repair deficient (dMMR) tumors and solid evidence supporting the addition of Olaparib for patients with pMMR.
For patients with dMMR, using Durvalumab plus chemotherapy followed by adjuvant therapy of Durvalumab produced better outcomes for patients with advanced endometrial cancer.
For patients with pMMR, there is compelling evidence for the addition of Olaparib to the maintenance Durvalumab treatment. They showed a longer duration of response (18.7 months) compared to the control arm (7.6 months) and had a 32% reduced risk of second progression or death than the control group. They also showed improvement in time from first to second treatments and other key secondary efficacy endpoints. Progression-free survival rates were much higher compared to those who received the standard of care alone, highlighting how the addition of Olaparib enhances the results of checkpoint inhibition immunotherapy as a first-line treatment for endometrial cancer.
DUO-E is the first phase III trial to explore the benefits of the combination of immunotherapy and PARP inhibition in patients with endometrial cancer. The results encourage further exploration of PARP inhibitor maintenance therapy in specific subsets of the disease, such as pMMR and PD-L1-positive patients. They also show promise of innovative new treatment approaches for patients with advanced forms of this disease.
The Future of Endometrial Treatment
Other initiatives to progress the treatment of endometrial cancer include exploring ways to detect it before symptoms develop, including studying genetic risk factors and new biomarkers. Treatment methods, such as using molecular subtypes to determine the best treatment options, employing targeted therapies, and testing treatment combinations, also allow us to advance our understanding and standard of care for endometrial cancer.
Clinical trials continue to push the needle forward in discovering and studying revolutionary drugs and treatments. Moffitt remains an active participant in these trials, giving our patients access to the most treatment options.
Moffitt is the only Florida–based National Cancer Institute (NCI) Designated Cancer Center. Our patients are cared for by a multidisciplinary team of experts in their fields, from gynecologic oncologists to medical oncologists, radiologists, fertility preservation specialists and more. Our tumor board meets weekly to evaluate patients and collectively determine individualized treatment plans. Moffitt is the best place for cancer care in Florida, with patient outcomes up to four times higher than the national average.
To refer a patient with a gynecologic cancer or with suspicious tumor finding, please complete our online form or contact a physician liaison for assistance. As part of our efforts to shorten referral times as much as possible, online referrals are typically responded to within 24 - 48 hours.