Evaluating Frontline Treatment Options for Low-Grade Serous Ovarian Cancer

CancerNetwork® spoke with Kathleen N. Moore, MD, MS, Virginia Kerley Cade Endowed Chair of Cancer Development, associate director of Clinical Research at the Stephenson Cancer Center, director of the Oklahoma TSET Phase I Program and professor in the Section of Gynecologic Oncology the University of Oklahoma Health Sciences Center, about first-line treatment options for low-grade serous ovarian cancer.

Moore began by stating that treatment in the first-line setting is evolving, suggesting that the standard of care is similar to high-grade serous ovarian cancer. She further expressed that current treatment includes primary cytoreduction, followed by paclitaxel and carboplatin. She further alluded to a retrospective study conducted by David M. Gershenson, MD and the MD Anderson Cancer Center which revealed that treatment with letrozole (Femara) in combination with primary cytoreduction and chemotherapy elicited enhanced progression-free survival (PFS) and overall survival (OS) outcomes vs primary cytoreduction and chemotherapy alone in patients with low-grade serous ovarian cancer.¹

She further expressed that some oncologists use bevacizumab (Avastin) as an active agent for low-grade serous ovarian cancer but suggests that most others use standard of care chemotherapy with letrozole. Furthermore, Moore identified studies wherein patients with low-grade serous ovarian cancer who underwent primary cytoreduction and bypassed chemotherapy experienced benefit with letrozole alone. Although she explained that the trials demonstrated a strong signal for the drug in this indication, she asserts that not enough data are available to suggest that it is a standard of care.

Moore then introduced the phase 3 NRG-GY019 trial (NCT04095364), which looks to assess letrozole with or without paclitaxel and carboplatin in patients with stage II to IV primarily resected low-grade serous ovarian cancer.² Led by Amanda Nickles Fader, MD, she stated that this trial will be impactful in investigating further standard of care treatment for this patient population. Moore concluded by explaining that the end points will not be evaluable for a number of years, considering the trial is only now almost finished with accrual and deals with a rarer and lower grade subtype of epithelial ovarian cancer.

Transcript:

First line treatment is evolving. The standard of care, ideally, is similar to high-grade serous ovarian cancer. It is primary cytoreduction, and I will come back to that point, followed by paclitaxel and carboplatin. There is retrospective data, although [primarily from a] single, large site at MD Anderson Cancer Center. This is [David M. Gershenson’s] work that looked at a population of patients who were primary cytoreduced and [received] chemotherapy with or without maintenance letrozole. The maintenance letrozole group retrospectively looked much better in terms of their PFS and OS. Even though the NCCN does not have a confirmed phase 3 study listed, I would consider that to be one of the leading options for standard of care in that setting.

Some will use bevacizumab. Bevacizumab [can be used] as an active agent in low-grade serous as well ... but I believe most are using chemotherapy and letrozole. There were [additional] small retrospective studies in patients who had undergone primary cytoreduction with near or complete resections who did not get chemotherapy at all and went directly onto letrozole, which is an aromatase inhibitor. Those small studies without control arms did demonstrate a strong signal that that could be an appropriate intervention. That also is listed as an option in the NCCN, although I am going to show my bias a bit. I do not think that is a standard of care. Others might disagree with me, but I do not think we have enough data yet to prove that.

That brings us to one of the more important clinical trials that just about completed accrual. It is through the National Cancer Institute, and it is called the NRG-GY019 trial, and it is led by Amanda Nickles Fader, MD, who published the first reports of letrozole alone. It [randomly assigns] patients with stage II to IV primarily resected low-grade serous ovarian cancer to [paclitaxel plus carboplatin], followed by letrozole vs letrozole [alone]. The end points, because it is lower grade, will probably take several years so we know the answer. It is a non-inferiority study. It is an incredibly important study, and we will have to wait and see what that looks like. Even though we are almost done with accrual, it is not going to read out for a number of years. I think that is the current standard of care.

References

1. Gershenson DM, Bodurka DC, Lu KH, et al. Impact of age and primary disease site on outcome in women with low-grade serous carcinoma of the ovary or peritoneum: results of a large single-institution registry of a rare tumor. 2015;33(24):2675-2682. doi:10.1200/JCO.2015.61.0873
2. Letrozole with or without paclitaxel and carboplatin in treating patients with stage II-IV ovarian, fallopian tube, or primary peritoneal cancer. ClinicalTrials.gov. Updated May 5, 2024. Accessed February 18, 2025. https://tinyurl.com/yprf2h8y