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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)
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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)

Amanda Fader, Austin Miller, Lilian Gien, Amy Deery, Colleen Rivard, Lauren Cobb, Rachel Grisham, Laura Holman, Kidong Kim, Christa Nagel, …
Gynecologic oncology, Vol.208(Supplement), pp.S452-S452
05/2026
DOI: 10.1016/j.ygyno.2026.02.023

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Abstract

Objectives To assess the efficacy and toxicity of Letrozole alone (L) versus paclitaxel and carboplatin followed by L (PC/L) as initial treatment for patients with stage II-IV, p53 wildtype, low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum. Methods NRG-GY019 is a phase III, noninferiority (NI) trial. After primary cytoreductive surgery (CRS), eligible subjects were randomized 1:1 to PC/L (paclitaxel and carboplatin IV, for up to six 21-day cycles) followed by L (PO once daily) or L alone (PO once daily). The randomization was stratified by 1) Country and 2) Residual disease following CRS (no gross—NGR–vs any residual disease). Progression-free survival (PFS) was the primary endpoint. The targeted 450 patient accrual supported 80% power (1-sided α = 0.1) to assess the NI of L (NI margin = 1.18) compared to PC/L. Two interim analyses were planned. Results Of 450 patients accrued, 3 were deemed ineligible, and 26 withdrew consent. The median patient age was 52, 92% had stage III/IV disease, and 64% had no gross residual (NGR) disease after CRS. In cycles 1–6, 100 PC/L and 38 L patients experienced at least one grade 3/4 event. Two grade 5 events on the Letrozole arm were considered unrelated to treatment. The odds of observing at least one grade 3/4 event was 4.26 (95%CI: 2.74, 6.62) higher in the PC/L patients than the L patients. The protocol-specified 2nd interim analysis assessed the futility or efficacy of L vs PC/L against a prespecified futility margin of HR ≥1.213 (lower values favor L). The interim analysis included 63 (L) and 50 (PC/L) PFS events, with a median follow-up time of 27.3 months. The HR estimate for L vs PC/L was 1.3 [95% CI: 0.9, 1.89], and the DSMB closed the study for futility of L. However, in the 64% (286/450) patients who underwent CRS to NGR, 29/142 (20.4%) of L patients experienced a progression event compared to 27/144 (18.8%) of PC/L patients, with an estimated HR at 1.15 [95% CI: 0.68–1.94]. The median PFS has not been reached in either treatment arm. At 18 months from randomization, 84% PC/L and 74% L patients were alive and progression-free. At the Jan 5, 2026 data cut off, 77.9% of PC/L and 71.9% of L patients remained alive and progression-free, with overall survival of 95% and 92%, respectively. Conclusions In the intent-to-treat population, the trial met the pre-specified criteria for early termination for futility and did not demonstrate noninferiority of L compared with PC/L. Ongoing follow-up and translational research are in progress. These results are practice-defining for PC/L as the current standard of care.

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