Letrozole monotherapy did not prove to be as effective as a combination of paclitaxel and carboplatin followed by letrozole for progression free survival in patients with newly diagnosed stage II-IV low grade serous carcinoma of the ovary or peritoneum, according to results from the phase III NRG GY019 trial presented on April 10 at the Society of Gynecologic Oncology Annual Meeting on Women's Cancer.
The findings are important for treatment planning, as they suggest that letrozole alone may not be sufficient for most patients, although certain subgroups could benefit.
At a median follow up of 27.3 months, researchers reported that the hazard ratio for letrozole alone compared to combination therapy was 1.30 (95% confidence interval: 0.90–1.89), which crossed the threshold set by study protocol for non inferiority. As of January 5, 2026, about 77.9% of patients receiving combination therapy and 71.9% receiving only letrozole remained alive and progression free; overall survival rates were reported at 95% and 92%, respectively.
The NRG-GY019 study enrolled 450 patients internationally after primary cytoreductive surgery and randomized them to receive either paclitaxel/carboplatin followed by letrozole or letrozole alone. The trial also found that serious side effects were more common in those who received combination therapy, with higher odds of experiencing at least one severe adverse event compared to those on monotherapy.
In an exploratory analysis among patients who had no apparent gross residual disease after surgery—a group with a better prognosis—the difference between treatment outcomes was smaller but still favored the combined approach.
"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." Translational endpoints from this research remain under analysis.
