Ribociclib Plus Letrozole Yields Meaningful Responses in Ovarian Cancer

Findings from a phase 2 clinical trial (NCT03673124) evaluating the combination of ribociclib (Kisqali) and letrozole in patients with recurrent low-grade serous carcinoma (LGSOC) of the ovary, fallopian tube, or peritoneum demonstrated that the combination therapy achieved meaningful response rates and durable disease control, meeting the study’s primary end point.^1,2

The trial reported a confirmed objective response rate of 30.6% (90% CI, 19.9%–43.2%), with a median duration of response (DOR) of 21.2 months. One patient achieved a complete response, and 14 patients achieved a partial response.

The clinical benefit rate (CBR) was 84% (90% CI, 72.5%–91.6%). Furthermore, the median progression-free survival (PFS) was 14.5 months (90% CI, 10.1–28.8), and the median overall survival (OS) reached 44.5 months.

The safety profile of the ribociclib and letrozole combination was consistent with the known adverse events (AEs) from prior studies of CDK4/6 inhibitors. The treatment was generally manageable.

The most frequent grade 3 or higher AE was neutropenia, which occurred in 47% of patients. AEs were effectively managed with dose modifications. No dose-limiting toxicities were observed during the trial. A low rate of patients (4%) had to discontinue treatment due to AEs. Three grade 5 events (fatalities), representing 6% of the treated population, occurred during the study; however, these were determined to be unrelated to the study treatment.

Study Rationale and Methodology

The trial was founded on a strong biological rationale for targeting LGSOC with a dual endocrine and CDK4/6 inhibitor approach. LGSOC is characterized by several key features that make it a suitable candidate for this combination therapy, including being hormonally driven; having a high estrogen receptor expression; CDK4/6 pathway dysregulation; and being chemoresistant. These characteristics are shared with hormone receptor–positive breast cancer, where the combination of endocrine therapy and CDK4/6 inhibition is an established strategy.

This study was a multicenter, open-label, single-arm phase 2 trial designed to assess the efficacy and safety of the combination treatment. The study enrolled 51 women (out of 74 screened) with measurable, recurrent LGSOC of the ovary, fallopian tube, or peritoneum. A total of 49 patients received treatment.

Patients received a combination of 600 mg of ribociclib administered orally, once daily, on days 1 through 21 of a 28-day cycle, and 2.5 mg of letrozole administered orally, once daily.

The study’s secondary end points included CBR, PFS, OS, and safety.

Patient Eligibility Criteria

Patient eligibility criteria included, but were not limited to, having never received a prior cyclin dependent kinase inhibitor; having no remaining ovarian function; and having an ECOG score of 0 to 2.

Patient ineligibility criteria included, but were not limited to, having a known hypersensitivity to ribociclib or letrozole; having a concurrent malignancy or malignancy within 3 years prior to the study; having an impairment of gastrointestinal function or disease; and having a known history of HIV infection.

Key Takeaways

The phase 2 trial concluded that the combination of ribociclib and letrozole provides a highly effective therapeutic option for patients with recurrent LGSOC. The regimen achieved its primary end point by demonstrating meaningful response rates and offered durable disease control as evidenced by the lengthy median DOR and PFS. The safety profile was predictable and manageable, further supporting its clinical utility.

“This combination represents a therapeutic option in this rare and genomically distinct subtype,” concluded Slomovitz et al, authors of the study.

REFERENCES

1.Slomovitz B, Weroha S, Deng W et al. Phase II trial of ribociclib plus letrozole in women with recurrent low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum: A GOG partners trial (GOG 3026). J Clin Oncol. Published December 12, 2025. Accessed January 2, 2026. doi: 10.1200/JCO-25-01348.

2.Ribociclib and letrozole treatment in ovarian cancer. ClinicalTrials.gov. Updated December 23, 2025. Accessed January 2, 2026. https://www.clinicaltrials.gov/study/NCT03673124