The aromatase inhibitor letrozole alone, without chemotherapy, may be sufficient to prevent disease progression after complete resection of low-grade serous ovarian carcinoma, according to a phase 3 noninferiority trial.

Chemotherapy is generally standard following resection, but response rates are low. With the addition of letrozole to treatment guidelines in recent years, it’s been unclear if chemotherapy — and its side effects — are still necessary.

To find out, the NRG-GY019 trial randomly assigned 450 women after cytoreductive surgery to either six cycles of paclitaxel/carboplatin followed by daily 2.5 mg letrozole until progression or to letrozole alone until progression. Lead investigator, Amanda Fader, MD, presented results of the trial at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer 2026.

How women fared seemed to depend on if they had residual disease after resection.

The trial was stopped early for futility after letrozole monotherapy exceeded the noninferiority threshold for disease-free progression (hazard ratio [HR], 1.18) in the intent-to-treat population, which included women both with and without complete R0 resections. At a median follow-up of 27.3 months, there were 63 progression events with letrozole alone vs 50 events in the combination arm (HR, 1.3).

However, in a subgroup analysis of the 64% of women who had R0 resections, letrozole monotherapy fell within the noninferiority threshold (HR, 1.15) with 29 progression events with letrozole monotherapy compared with 27 events with combination treatment; the difference was not statistically significant.

Among women on letrozole monotherapy, the rate of recurrence was 41.5% if they had residual disease after surgery but 20.5% if they did not.

In short, “a clinically relevant subset of patients may be appropriate candidates for letrozole monotherapy.” Additional follow-up and investigation “are essential to better contextualize these observations and determine whether letrozole alone may be a reasonable alternative” after R0 resection, said Fader, who is a gynecologic oncologist with John Hopkins Medicine. 

Study discussant Roisin O’Cearbhaill, MD, gynecologic medical oncologist at Memorial Sloan Kettering Cancer Center, New York City, agreed. 

Although GY0219 closed early for futility, “it may be possible with careful discussion and patient selection that there is a subset of patients that we could move away from chemotherapy,” she said.

For now, Fader said the findings remain hypothesis-generating; the trial was not powered to demonstrate noninferiority following R0 resection, and CIs were wide.

As expected, the odds of grade 3/4 events were four times higher in the chemotherapy/letrozole arm, primarily due to hematologic, gastrointestinal, and neurologic toxicities, she said.

The trial included women with stages 2-4, p53 wild-type, low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum. Participants had a median age of 52 years; 96% were in the US or Canada; 86% were White, and 92% had stage 3/4 disease.

The trial launched in 2019. Across the entire cohort as of January 2026, 77.9% of combination patients and 71.9% of letrozole patients are alive and progression-free, with overall survival rates of 95% and 92%, respectively.

The work was funded by the National Cancer Institute. Fader disclosed ties to GSK. O’Cearbhaill is an advisor for GSK, Pfizer, AstraZeneca, AbbVie, and other companies.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@medscape.net.