Determining Standard of Care First-Line Treatment in Advanced, Low-Grade Serous Ovarian Carcinoma

By: Lisa Astor
Posted: Monday, May 18, 2026

Letrozole monotherapy did not show noninferiority compared with chemotherapy followed by letrozole in patients with advanced, low-grade serous ovarian carcinoma, according to results from the phase III noninferiority NRG-GY019 trial presented at the 2026 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer.

“This is a practice-defining trial and establishes carboplatin/paclitaxel and letrozole as the standard of care,” said presenting author Amanda N. Fader, MD, Vice Chair of Gynecologic Surgical Operations, Johns Hopkins Health System; Director, Center for Rare Gynecologic Cancers; and Professor of Gynecology and Obstetrics, Johns Hopkins Medicine.

NRG-GY019 sought to determine if chemotherapy could safely be removed in patients with advanced low-grade serous ovarian cancer. The researchers explored the efficacy and safety of letrozole monotherapy vs paclitaxel and carboplatin chemotherapy followed by letrozole as first-line treatment in patients with stage II to IV, p53 wild-type, low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum (n = 421).

Patients were randomly assigned to the monotherapy or combination treatment arm after primary cytoreductive surgery, with stratification by country and residual disease after surgery. In the combination treatment arm, intravenous paclitaxel and carboplatin were administered for up to six cycles of 21 days each followed by letrozole orally once daily. The primary endpoint was progression-free survival.

Letrozole monotherapy did not achieve noninferiority vs chemotherapy followed by letrozole (hazard ratio [HR] = 1.30; 95% confidence interval [CI] = 0.90–1.89; one-sided P = .6977). At one year, the progression-free survival rate was 80% with letrozole monotherapy and 91% with chemotherapy and letrozole. The HR for overall survival was 1.52 (95% CI = 0.73–3.13).

The phase III trial met the prespecified futility stopping criteria.

In terms of safety, the odds of observing at least one grade 3/4 adverse event during the first six cycles was 3.99 times higher (95% CI = 2.57–6.18; P < .001) among patients on the combination treatment arm vs the letrozole monotherapy arm.

A prespecified hypothesis-generating analysis looked at progression-free survival in patients who achieved no gross residual disease after surgery. In this group (n = 286), the HR for progression-free survival was 1.15 (95% CI = 0.68–1.94; one-sided P = .4560). In the letrozole monotherapy arm, 20.5% of patients with no gross residual disease had disease recurrence vs 41.5% of patients who had residual disease.

“Although exploratory, this finding is provocative and raises the possibility that a clinically relevant subset of patients may be appropriate candidates for letrozole monotherapy,” Dr. Fader said.

Disclosures: The research was supported by grants from NRG Oncology Operations and NRG Oncology SDMC. Dr. Fader reported a financial relationship with GSK.

2026 SGO Annual Meeting on Women’s Cancer

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