Key Clinical Summary:

• Design/Population: The phase 3 NRG-GY019 trial randomized 450 patients with stage II to IV low-grade serous carcinoma after cytoreductive surgery to receive chemotherapy followed by letrozole or letrozole alone. The primary end point was progression-free survival.
• Key Outcomes: Letrozole monotherapy did not meet noninferiority criteria compared with chemotherapy followed by letrozole and the study was stopped early for futility. Chemotherapy was associated with higher toxicity, but improved disease control.
• Clinical Relevance: These findings support chemotherapy followed by letrozole as the standard frontline approach in this population. Endocrine therapy alone may still be considered in selected patients but cannot replace chemotherapy. 

Results from the phase 3 NRG-GY019 trial confirm that letrozole alone is inferior to chemotherapy followed by letrozole among patients with low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum. 

These findings were presented by Amanda Fader, MD, Johns Hopkins Medicine, Baltimore, Maryland, at the 2026 Society of Gynecologic Oncology (SGO) Annual Meeting in San Juan, Puerto Rico.

In this noninferiority trial, researchers enrolled 421 patients with stage II to IV, p53 wild-type low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum who underwent primary cytoreductive surgery. Patients were randomized 1:1 to receive either paclitaxel plus carboplatin (for up to six 21-day cycles) followed by once daily letrozole or letrozole alone. Patients were stratified by country and presence of residual disease following cytoreductive surgery (no gross residual disease n = 286; any residual disease n = 135). The primary end point was progression-free survival (PFS). Key secondary end points included overall survival (OS) and safety. 

At a median follow-up of 27.3 months, median PFS was not reached in either treatment arm (hazard ratio [HR], 1.30), with PFS events occurring in 50 patients in the combination arm and 63 patients in the letrozole arm. The 18-month PFS rates were 84% and 74%, respectively. At the data cutoff point, PFS rates were 77.9% in the combination arm and 71.9% in the letrozole arm, and OS was 95% and 92%, respectively. 

The study was closed early for futility and did not demonstrate noninferiority of letrozole monotherapy. However, in the subgroup of patients who achieved no gross residual disease after surgery, progression events were observed in 18.8% of patients in the combination arm and 20.4% of patients in the letrozole arm (HR, 1.15).

Throughout cycles 1 through 6, at least 1 grade 3/4 adverse event was reported among 100 patients in the combination arm and 38 patients in the letrozole arm. The odds of experiencing at least 1 grade 3/4 was 4.26 times higher in the combination arm, compared to the letrozole arm. Two deaths were reported in the letrozole arm deemed unrelated to treatment. 

“In the intent-to-treat population, the trial met the pre-specified criteria for early termination for futility and did not demonstrate noninferiority of [letrozole] compared with [paclitaxel plus carboplatin followed by letrozole],” concluded Dr Fader et al. “These results are practice-defining for [paclitaxel plus carboplatin followed by letrozole] as the current standard of care.” 

Source: 

Fader A, Miller A, Gien L, et al. Results of a randomized phase III trial of letrozole alone versus paclitaxel and carboplatin followed by letrozole as initial treatment for patients with stage II-IV ovarian, fallopian tube, or primary peritoneal low-grade serous carcinoma (NRG-GY019, NCT04095364). Presented at SGO Annual Meeting on Women’s Cancer. April 10 - 13, 2026; San Juan, Puerto Rico. LBA2.