The invited discussant of the phase II feMMe trial1 was Angeles Alvarez Secord, MD, Professor of Obstetrics and Gynecology, Duke University School of Medicine, Durham, North Carolina. She noted that, because of its “alarming” increase in incidence and mortality, endometrial cancer is “a critically important area to study.”
“One of the things that most interested me in this study is the remarkable weight loss that was seen across these various arms. In my clinical experience and based on the research we have conducted, it is difficult for patients with endometrial cancer to lose weight, even with counseling, and most often these women continue to gain weight,” she said. An unanswered question, of course, is whether this weight loss will be sustained, she added.
Dr. Alvarez Secord also expressed disappointment that the rates of pathologic complete response were not higher among women with endometrial cancer. “Although the pathologic complete response results in the women with atypical endometrial hyperplasia were very reassuring (82%), the findings in endometrial cancer (43%) were lower than I expected,” she said.
Cautious Optimism Moving Forward
Some studies of levonorgestrel intrauterine devices have reported pathologic complete response rates of up to 95%, she pointed out, but she acknowledged that many of them were retrospective or observational, and prospective studies were mostly single-armed. Therefore, this randomized trial provided important data, Dr. Alvarez Secord said.
The underlying biology of the tumors in this study may have played a role in the lower response rates, Dr. Alvarez Secord proposed. In a study from her institution, patients with copy-number-high tumors were observed to have a much shorter time to disease progression or definitive therapy.2 “This highlights the importance of understanding the molecular biology in early-stage endometrial cancer, to inform our decision-making and management,” she said. “The underlying molecular biology and proteomic expression will inform both future trial design and therapeutic target prioritization.”
DISCLOSURE: Dr. Alvarez Secord has received honoraria from Arivave, Clovis Oncology, Eisai, Merck, Myriad Genetics, and Tesaro/GSK; has served as a consultant or advisor to Arivave, Clovis Oncology, Eisai, Merck, and Tesaro; has received institutional research funding from AbbVie, AstraZeneca, Boehringer Ingelheim, Clovis, Eisai, Genentech, GlaxoSmithKline, Immutep, Merck, OncoQuest Pharmaceuticals, PharmaMar, Seattle Genetics, Tesaro, and VBL Therapeutics; and has held uncompensated relationships with the GOG Foundation, OncoQuest Pharmaceuticals, Roche/Genentech, and VBL Therapeutics.
REFERENCES
1. Janda M, Robledo K, Gebski V, et al: Complete pathological response following levonorgestrel intrauterine in clinical stage 1 endometrial adenocarcinoma: Results of a clinical trial (feMMe trial, ANZGOG1301). SGO 2021 Annual Meeting on Women’s Cancer. Abstract 72. Presented March 21, 2021.
2. Puechi AM, Spinosa D, Berchuck A, et al: Turning ProMisE into practice: Predicting response in medically managed endometrial cancers via molecular classification. SGO 2020 Annual Meeting on Women’s Cancer. Abstract 29. Presented March 29, 2020.
