Amanda Nickles Fader, MD, Professor of Gynecology and Obstetrics, Professor of Oncology, and Vice Chair of Gynecologic Surgical Operations at Johns Hopkins Health System, Baltimore, provided her thoughts on GOG 3026 for The ASCO Post.
Dr. Fader applauded the investigators and the Gynecologic Oncology Group for conducting GOG 3026, which she said “represents an important step forward in the treatment of women with low-grade serous ovarian carcinoma.” As Dr. Fader pointed out, for more than 2 decades, the treatment of advanced ovarian cancer has involved cytotoxic chemotherapy. But recent advances in the understanding of tumor biology, occurring in an era of big data and molecular/genomic classification of tumors, has revealed that patients with low-grade epithelial ovarian cancers may benefit from treatments other than cytotoxic agents.
“There is a quiet revolution happening in cancer care with the approval and utilization of many new therapeutics and a concurrent move away from cytotoxic chemotherapy. The concept of foregoing cytotoxic therapy is gaining traction in several tumor types, including breast cancer and low-grade ovarian malignancies.1 For instance, most women with hormone receptor–positive, HER2-negative, low-grade breast cancers are now treated with endocrine combination therapies instead of chemotherapy. This includes the combination analyzed in GOG-3026, letrozole and ribociclib, which in phase III trials has demonstrated improved survival for women with advanced or recurrent breast cancer when compared to endocrine therapy alone,2” Dr. Fader said.
Amanda Nickles Fader, MD
“Increased expression of cyclin-depedent kinases 4 and 6 (CDK4/6), which play a critical role in regulating cell cycle progression, drives resistance to endocrine therapies in patients with hormone receptor-positive cancers. Therefore, inhibiting this mechanism is crucial to improving response rate to endocrine treatments like letrozole. There are similarities between breast cancer and low-grade serous carcinoma in terms of tumoral grade and hormonal expression profiles, so it makes sense to study similar therapies,” she said.
“It was exciting to see that in the phase II GOG 3026 trial, one in four women durably responded to letrozole/ribociclib, and four of five women experienced some form of clinical benefit from the combination therapy. The combination was also well tolerated. These impressive trial data add to the breakthrough results of an unpublished phase II trial conducted at the MD Anderson Cancer Center demonstrating excellent neoadjuvant activity (60% objective response rate) of abemaciclib (a CDK4/6 inhibitor) and fulvestrant in 15 women with advanced low-grade serous ovarian cancer,3” she said.
“In the United States, the current standard treatment for women with advanced-stage low grade serous carcinoma includes maintenance letrozole therapy. Given that prior letrozole therapy was an exclusion criterion in the GOG 3026 trial, a question I have for the study authors is whether letrozole/ribociclib will be a relevant therapeutic choice for patients who have received prior treatment with letrozole. While additional studies will be needed, letrozole could potentially be substituted with fulvestrant in this situation, as has been done in the breast cancer treatment paradigms,” Dr. Fader suggested. “I congratulate Dr. Slomovitz and the GOG study team, again, for their outstanding efforts to advance ovarian cancer outcomes for women with low-grade serous ovarian tumors.”
DISCLOSURE: Dr. Fader is principal investigator of the NRG Oncology GY019 trial and has received support from Verastem.
1. Kolata G: Cancer without chemotherapy: A totally different world. The New York Times. Available at https://www.nytimes.com/2021/09/27/health/breast-cancer-chemotherapy-lung.html. Accessed April 4, 2023.
2. Horobagyi GN, Stemmer SM, Burris HA, et al: Overall survival with ribociclib plus letrozole in advanced breast cancer. N Engl J Med 386:942-950, 2022.
3. Cobb LP, Davis J, Hull S, et al. A pilot phase II study of neoadjuvant fulvestrant plus abemaciclib in women with advanced low-grade serous carcinoma. J Clin Oncol 40(suppl 16):55522, 2022.
In patients with recurrent low-grade serous ovarian cancer, treatment with ribociclib plus letrozole was not only active, but led to outcomes that are comparable to those achieved with current agents—with a particularly striking 19-month duration of response—according to Brian M. Slomovitz, MD,...