Shannon N. Westin, MD, MPH

Shannon N. Westin, MD, MPH, FACOG, an associate professor, Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery at the University of Texas MD Anderson Cancer Center, discusses the endometrial cancer patient population enrolled in the phase 3 DUO-E trial (NCT04269200).

The randomized, multicenter, double-blind, placebo-controlled study examines the efficacy and safety of durvalumab in combination with platinum-based chemotherapy, paclitaxel plus carboplatin, followed by maintenance durvalumab (Imfinzi) with or without olaparib (Lynparza) as treatment for patients with newly-diagnosed advanced or recurrent endometrial cancer.

Enrolled patients are females aged 18 and older with histologically confirmed epithelial endometrial carcinoma, excluding sarcomas. Requirements also include having systemic anti-cancer agents, an ECOG performance status of 0 or 1, and a tumor sample available for testing.

The primary end point of the study is progression-free survival with secondary end points including overall survival, second progression, objective response rate, duration of response, safety, as well as other efficacy end points.

 One of the things that we made sure of is to include several patients that are even at higher risk. Many of these types of trials will exclude patients who have carcinosarcoma, which is one of the more aggressive subtypes. But we are including that in our trials. So, we're excited to see if we can get benefit for that patient population.

 In addition, we are allowing patients to have prior chemotherapy, so those patients that have recurrent endometrial cancer can have had prior chemotherapy if it's been more than a year. So that's a few of the unique pieces of this trial that will hopefully expand eligibility, and also, give us an idea of the activity and all these different populations.

Videos

Shannon N. Westin, MD, MPH, FACOG, discusses the endometrial cancer patient population enrolled in the phase 3 DUO-E trial.

DUO-E Trial Focuses on Treating High-Risk Endometrial Cancer

Shannon N. Westin, MD, MPH, FACOG, director of Early Drug Development and Phase I Trials in the Department of Gynecologic Oncology and Reproductive Medicine of the Division of Surgery at the University of Texas MD Anderson Cancer Center, discusses the evolving role of immunotherapy as treatment of patients with endometrial cancer. She says there is a lot of excitement surrounding this approach in these patients.

About 20% to 30% of patients with endometrial cancer will have microsatellite instability–high (MSI-H) disease, so they are eligible for checkpoint inhibitor monotherapy. At the Society of Gynecologic Oncology Annual Meeting, an update for the GARNET trial was presented, which demonstrated promising response rates a little over 40% in tumors that were MSI-H with dostarlimab, a PD-1 inhibitor, says Westin.

The other population of patients with endometrial cancer are those with microsatellite stable (MSS) disease, which makes up about 70% to 80% of uterine tumors, Westin says. Vicky Makker, MD, of Memorial Sloan Kettering Cancer Center, shared the data from the combination of lenvatinib (Lenvima) plus pembrolizumab (Keytruda), another checkpoint inhibitor. This approach seemed to achieve the sensitivity to checkpoint inhibition in these tumors without MSI.

The combination achieved durable and deep remissions, and in those patients, when they responded, their duration of response was not reached yet, Westin notes. The combination received approval from the FDA based on these findings in patients with MSS disease. The combination is also being evaluated in comparison with chemotherapy.

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Shannon N. Westin, MD, MPH, FACOG, discusses the evolving role of immunotherapy as treatment of patients with endometrial cancer.

Immunotherapy Advances the Treatment Landscape of Endometrial Cancers

Shannon N. Westin, MD, MPH, clinical investigator, Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, discusses resistance seen with PARP inhibitors in ovarian cancer and how this resistance can be overcome.

Westin says that she predominantly sees resistance after what she calls the &ldquo;treatment phase&rdquo; rather than in patients given PARP inhibitors in the maintenance setting. These patients experiencing resistance often have either germline or somatic

mutations and were treated with single-agent PARP inhibitors in the recurrent setting.

Shannon N. Westin, MD, MPH, discusses resistance seen with PARP inhibitors in ovarian cancer and how this resistance can be overcome.

Shannon N. Westin, MD, MPH | Authors

Articles

DUO-E Trial Focuses on Treating High-Risk Endometrial Cancer

Immunotherapy Advances the Treatment Landscape of Endometrial Cancers

Overcoming Resistance to PARP Inhibitors in Ovarian Cancer