Updated results from the phase III NRG GY019 trial show that letrozole monotherapy (L) is noninferior 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 second protocol-specified interim analysis (median follow-up 27.3 months), the hazard ratio (HR) for L versus PC/L was 1.30 (95% CI, 0.90 to 1.89), exceeding the prespecified futility/noninferiority margin (HR > 1.213). As of data cutoff on January 5, 2026, 77.9% of PC/L patients and 71.9% of L patients were alive and progression-free, with overall survival rates of 95% and 92%, respectively. These results were presented at the opening plenary session of the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer, held on April 10, 2026.
NRG-GY019 was designed as an international phase III non-inferiority trial comparing both treatment options after initial cytoreductive surgery. Patients were enrolled and stratified by postoperative residual disease status and country after cytoreductive surgery. Patients were then randomized to receive paclitaxel and carboplatin followed by letrozole (PC/L) or letrozole alone (L). This study included 450 patients and considered 80% power (one-sided α=0.1) to assess the non-inferiority of L compared to PC/L by PFS. Two interim analyzes were planned during the study.
PC/L was associated with significantly more severe side effects than L monotherapy, and the odds of experiencing at least one grade 3-4 event were higher in the PC/L treatment group (OR 4.26; 95% CI, 2.74-6.62). Furthermore, in an exploratory analysis of 286 study patients (64% of the study population) who underwent cytoreductive surgery (NGR) until there was no apparent gross residual disease (a subgroup with a more favorable prognosis), the difference in PFS outcomes between treatment groups was smaller, with a noninferiority hazard ratio of 1.15 (95% CI, 0.68 to 1.94).
This is the first Phase III frontline trial to complete enrollment in rare ovarian cancer and is a milestone demonstrating that collaborative group institutions, treating oncologists, and patient advocates can work together to plan and successfully recruit patients for rare tumor research. NRG-GY019 is a practice-defining trial, establishing PC/L as the standard approach for patients with advanced low-grade serous ovarian cancer. ”
Amanda Fader, MD, first author of the NRG-GY019 abstract, director of the Rare Gynecologic Cancer Center, and professor of gynecology, obstetrics, and oncology at Johns Hopkins Hospital
Translational endpoints remain under analysis and will be reported as they become available.
“Our hypothesis-generating analysis in patients with post-surgical NGR disease is provocative and raises the possibility that a clinically relevant subset of patients may be suitable candidates for L monotherapy,” Fader says. “Ongoing clinical follow-up and planned correlative tumor molecular profiling are essential to contextualize these observations, identify which patients benefit most from PC/L, and determine whether L alone may be a reasonable option in specific patients.”
This project was supported by grants U10CA180868 (NRG Oncology Operations) and U10CA180822 (NRG Oncology SDMC) from the National Cancer Institute (NCI).
