David M. O’Malley, MD, director of the Division of Gynecologic Oncology at the Ohio State University Comprehensive Cancer Center-The James and professor in the Department of Obstetrics and Gynecology at The Ohio State University College of Medicine, spoke with CancerNetwork® about where treatment efforts for patients with endometrial cancer, specifically those with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) disease, are being focused.

The next steps are so exciting. We have multiple first-line trials in metastatic and recurrent therapies as well as locoregional disease, meaning disease that has been completely removed and has a positive lymph node. We also have a trial which is looking at patients with early-stage disease who are at intermediate risk of recurrence and combining pembrolizumab [Keytruda] with radiation. In addition, maybe one of the most exciting options that we will consider is in patients who have dMMR deficient or MSI-H [disease. Treating those] patients with pembrolizumab vs the standard therapy of carboplatin plus paclitaxel, we may be replacing the cytotoxic agents with a single immune therapy. The future is bright for our patients with uterine cancer, thanks to immune therapies.

Videos

David M. O’Malley, MD, spoke about where the future of treatment is heading for patients with endometrial cancer. 



David M. O’Malley, MD, Talks Next Steps for Treatment in Endometrial Cancer

Pembrolizumab (Keytruda) was recently approved for patients with advanced endometrial carcinoma that is microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR), based on results of the phase 2 KEYNOTE-158 trial (NCT02628067).

 CancerNetwork® spoke with David M. O’Malley, MD, director of the Division of Gynecologic Oncology at the Ohio State University Comprehensive Cancer Center-The James and professor in the Department of Obstetrics and Gynecology at The Ohio State University College of Medicine as well as lead investigator of the study, about which patient populations benefit most from this treatment and how the agent is helping to address unmet needs for these patients.

This is giving patients with recurrent metastatic uterine cancer an option which we could never have dreamed of prior to these checkpoint inhibitors. In the past, the options were quite limited in patients with recurrent uterine cancer, and there was no differentiation between [disease that was] MSI-H or dMMR deficient. This is a great step into personalized medicine and using the molecular changes within tumors to help us differentiate care and treatments.

The approval is for MSI-H and dMMR deficient disease, and those are clearly the patients which will benefit. Mismatch repair–proficient or MSI stable patients should not be treated with single-agent pembrolizumab. Those patients have an option of pembrolizumab plus lenvatinib [Lenvima] with immune therapies. It’s very important that we prescribe the proper therapies specifically to those patients who are MSI-H or dMMR deficient.

FDA approved pembrolizumab for advanced endometrial carcinoma. News Release. FDA. March 21, 2022. Accessed April 26, 2022. https://bit.ly/3ke9WFS

O’Malley DM, Bariani GM, Cassier PA, et al. Pembrolizumab in patients with microsatellite instability-high advanced endometrial cancer: Results from the KEYNOTE-158 Study. 

. 2022;40(7):752-761. doi:10.1200/JCO.21.01874

David M. O’Malley, MD, spoke about unmet needs of patients with advanced microsatellite instability–¬high or mismatch repair deficient endometrial carcinoma and the clinical benefit pembrolizumab provides.

David M. O’Malley, MD, Reviews the Benefit of Pembrolizumab for Endometrial Cancer

David M. O’Malley, MD, director of the Division of Gynecologic Oncology at the Ohio State University Comprehensive Cancer Center-The James and professor in the Department of Obstetrics and Gynecology at The Ohio State University College of Medicine, spoke with CancerNetwork® about the recent approval of pembrolizumab (Keytruda) for patients with advanced endometrial carcinoma that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).

The phase 2 KEYNOTE-158 trial (NCT02628067), for which O’Malley was the lead investigator, led to the approval of this treatment. In total, 90 patients received pembrolizumab at 200 mg intravenously every 3 weeks until unacceptable toxicity or disease progression.

Patients had an objective response rate of 48% (95% CI, 37%- 60%), and the duration of response was not reached. 

What [is important for] these patients is an option beyond chemotherapy. In the past, the chemotherapy [options] after carboplatin and paclitaxel was quite limited in its response rate and duration of responses of only 3 to 4 months. When we see the data with regards to the recent update and publication in the 

, we see response rates of 48%. If you get a response, the chance that response lasts more than or equal to 3 years is approximately two-thirds. These are durable, long-lasting responses, and we may be talking about curative intent in patients with recurrent uterine cancer that is MSI-H or dMMR deficient.

David M. O’Malley, MD, spoke about the approval of pembrolizumab for patients with advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient.

Pembrolizumab for Advanced MSI-H/dMMR Endometrial Cancer | Videos

EP. 1: David M. O’Malley, MD, Talks Next Steps for Treatment in Endometrial Cancer

EP. 2: David M. O’Malley, MD, Reviews the Benefit of Pembrolizumab for Endometrial Cancer

EP. 3: David M. O’Malley, MD, Discusses Recent Approval of Pembrolizumab in Endometrial Cancer