SAN JUAN, PR – Late breaking results from the phase III NRG GY019 trial indicate that letrozole monotherapy (L) did not demonstrate non inferiority to paclitaxel/carboplatin followed by letrozole (PC/L) for progression free survival (PFS) in patients with newly diagnosed stage II-IV low grade serous carcinoma of the ovary or peritoneum. At the protocol specified second interim analysis (median follow up 27.3 months), the hazard ratio (HR) for L versus PC/L was 1.30 (95% CI, 0.90–1.89), crossing the prespecified futility/non inferiority margin (HR > 1.213). As of the January 5, 2026 data cutoff, 77.9% of PC/L and 71.9% of L patients remained alive and progression free, and overall survival rates of 95% and 92%, respectively. These results were presented on April 10th, 2026 at the Opening Plenary Session of the Society of Gynecologic Oncology Annual Meeting on Women's Cancer.
NRG-GY019 was designed as an international, phase III, noninferiority trial comparing both treatment options after primary cytoreductive surgery. Patients were enrolled and stratified by residual disease status after surgery and country following cytoreductive surgery. Patients were then randomized to receive either paclitaxel and carboplatin followed by letrozole (PC/L) or letrozole alone (L). This study included 450 patients which allowed for 80% power (1-sided α=0.1) to assess the noninferiority of L compared to PC/L by PFS. Two interim analyses were planned during the study.
PC/L was associated with significantly more serious side effects than L monotherapy, with the odds of experiencing at least one grade 3–4 event higher in the PC/L treatment arm (OR 4.26; 95% CI, 2.74–6.62). Additionally, in an exploratory analysis of the 286 study patients (64% of the study population) who underwent cytoreductive surgery to no apparent gross residual (NGR)--a subgroup with more favorable prognosis—the difference in the PFS outcomes between treatment arms was smaller, with a non-inferiority hazard ratio of 1.15 (95% CI, 0.68–1.94).
"This is the first Phase III frontline trial in rare ovarian cancer to complete enrollment — a milestone that demonstrates cooperative group sites, treating oncologists, and patient advocates can work together to design and successfully recruit patients for rare-tumor studies. NRG-GY019 is a practice-defining trial, establishing PC/L as the standard approach for patients with advanced low-grade serous ovarian carcinoma," said Amanda Fader, MD, the lead author of the NRG-GY019 abstract and Director of the Center for Rare Gynecologic Cancers and Professor in the Departments of Gynecology and Obstetrics and Oncology at Johns Hopkins Hospital.
Translational endpoints remain under analysis and will be reported when available.
"The hypothesis-generating analysis in patients with NGR disease after surgery is provocative and raises the possibility that a clinically relevant subset of patients may be appropriate candidates for L monotherapy", says Fader. "Ongoing clinical follow up and planned correlative tumor molecular profiling are essential to contextualize these observations, identify which patients derive the greatest benefit from PC/L, and determine whether L alone may be a reasonable alternative in select patients."
This project was supported by grants U10CA180868 (NRG Oncology Operations) and U10CA180822 (NRG Oncology SDMC) from the National Cancer Institute (NCI).
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