Key Advances in Endometrial Cancer - Episode 10

Therapy Sequencing Through Multiple Lines of Therapy in EC


David M. O’Malley, MD: Let’s talk about the sequencing in patients with recurrent or advanced uterine cancer. As I’ve said, carboplatin-paclitaxel is my backbone. I’m always looking for a clinical trial, particularly in advanced and recurrent patients. We have to do better for these patients. What happens if they’re not a candidate for a clinical trial—if they were just diagnosed with breast cancer and it excludes them? My backbone is carboplatin-paclitaxel. I’ll utilize that in the recurrent disease to tolerance or toxicity. The reason being that I don’t have very good luck getting complete responses in people, and like in ovarian cancer, stop them and maintain them.

However, I recently have utilized the carboplatin-paclitaxel, and if they have a tumor that is low grade or ER+ [estrogen receptor positive] or PR+ [progesterone receptor positive], I switch them to a hormonal-based therapy like aromatase inhibitors. I’ve used tamoxifen-based combination—probably 1 of the most underutilized combinations that we have. It’s well studied in the GOG [Gynecologic Oncology Group], usually very well tolerated, and it gives them a break from the cytotoxic drugs. If after 6 to 8 cycles of the cytotoxic they’re starting to get toxicities, look to transition them into a better-tolerated regimen like hormonal therapy.

If they have a serous cancer and they’re HER2 [human epidermal growth factor receptor 2]/neu positive, then I obviously continue the trastuzumab. I stop the backbone of the carboplatin-paclitaxel after 6 cycles, then I continue trastuzumab until toxicity or progression. If a patient progresses through carboplatin-paclitaxel and they’re MSI [microsatellite instability] high or MMR [mismatch repair] deficient, then it’s really easy: pembrolizumab. If they’re proficient, it’s really easy: lenvatinib-pembrolizumab.

If a patient has a great response or it’s been years since they’ve seen carboplatin-paclitaxel because they’ve received it for adjuvant therapy, I may go back to carboplatin-paclitaxel. But if they’re proficient or deficient, I look for immunotherapy. The response rates there are amazing. Unlike chemotherapy in the recurrent setting, I do see complete responses. It’s probably only about 10% of patients, but I do see complete responses.

Transcript Edited for Clarity