Subgroup-Targeted Agents Are Needed for Endometrial Cancer

Bhavana Pothuri, MD, professor in the Department of Obstetrics and Gynecology and Department of Medicine at NYU Grossman School of Medicine, and director of Gynecologic Oncology Clinical Trials at NYU Langone Health’s Perlmutter Cancer Center, discusses ongoing and potential studies of copy-number low and high subgroups of patients with endometrial cancer.

The combination of lenvatinib (Lenvima) and pembrolizumab (Keytruda) showed efficacy in some subgroups of endometrial cancer in the KEYNOTE-775 trial (NCT03517449). According to Pothuri, more research is needed for the copy-number low subgroup, which is correlated to lower-grade endometrioids that are responsive to hormonal therapy. Megestrol acetate, which is a common frontline option for these patients, was approved for treatment of endometrial cancer in 1971 and newer options could improve its fairly short progression-free survival (PFS).

Pothuri suggests that combinations of hormonal therapy with CDK4/6 inhibitors could be effective in this subgroup, as established by the phase 2 ENGOT-EN3/NSGO-PALEO study (NCT02730429) of palbociclib (Ibrance) plus the aromatase inhibitor letrozole.

The copy-number high group is also in need of targeted inhibitors based on specific ERBB2 mutations, Pothuri says. More information is needed on the role of trastuzumab (Herceptin) following its demonstration of improved PFS with chemotherapy in a phase 2 trial (NCT01367002) of patients with advanced HER2-positive uterine serous carcinoma. Ongoing and future studies will offer better outcomes by targeting the key subgroups of patients with endometrial cancer.

TRANSCRIPTION:

0:08 | While [lenvatinib/pembrolizumab] is efficacious, can we look at this subset even further and look at the copy-number low group which is more of the endometrioids that are grade 1 that may be responsive to hormones? At present, all we have approved in terms of hormonal therapy is megestrol acetate, which was approved in 1971, with response rates that are between around 20%, but really short PFS, 2 and a half to 3 months. So, I think looking at that subgroup and further evaluating data, like the role of CDK4/6 inhibitors with hormonal therapy, like the PALEO study did, is going to be important.

Then also now branching to the other side and looking at the copy-number high [subgroup], can we look at specific ERBB2 mutations and the role of trastuzumab or other combinations as well as the role of—we want inhibitors in that copy-number high subgroups. So I think we've definitely started to make progress in our understanding, but I think there's more to come. And we're already kind of seeing that as some of these studies are ongoing.