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)

Abstract

PURPOSE Low-grade serous carcinoma (LGSOC) of the ovary, fallopian tube, or peritoneum is a hormonally driven, relatively chemoresistant malignancy with limited treatment options in the recurrent setting. Given frequent estrogen receptor (ER) expression and dysregulation of the cyclin-dependent kinases 4 and 6 (CDK4/6)–p16–Rb pathway, features shared with hormone receptor–positive breast cancer, dual endocrine, and CDK4/6 inhibition is a biologically rational strategy. This phase II trial evaluated ribociclib plus letrozole in recurrent LGSOC. METHODS This open-label, single-arm, multicenter phase II study enrolled women with measurable, recurrent LGSOC. Patients received ribociclib (600 mg orally, once daily, days 1-21 of a 28-day cycle) and letrozole (2.5 mg orally, once daily). The primary end point was investigator-assessed objective response rate (ORR) per RECIST 1.1. Secondary end points included clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS Of 74 patients screened, 51 were enrolled and 49 treated. The confirmed ORR was 30.6% (90% CI, 19.9 to 43.2), including one complete and 14 partial responses. Among responders, the median duration of response was 21.2 months. The CBR was 84% (90% CI, 72.5 to 91.6). The median PFS was 14.5 months (90% CI, 10.1 to 28.8), and the median OS was 44.5 months (90% CI, 31.8 to not reached). The most common grade ≥3 adverse event (AE) was neutropenia (47%), managed with dose modifications. Three grade 5 events (6%) occurred but were unrelated to treatment. Treatment discontinuation because of AEs occurred in 4%. No dose-limiting toxicities were observed. CONCLUSION Ribociclib plus letrozole met the primary end point, achieving meaningful response rates and durable disease control in recurrent LGSOC. The safety profile was consistent with prior CDK4/6 inhibitor studies. This combination represents a therapeutic option in this rare and genomically distinct subtype.

Affiliated Institutions

• Texas Oncology US
• University of New Mexico US
• Northside Hospital US
• UNM Comprehensive Cancer Center
• The University of Texas MD Anderson Cancer Center US
• University of Oklahoma Health Sciences Center US
• Houston Methodist Sugar Land Hospital US
• NorthShore University HealthSystem US
• The US Oncology Network US
• Roswell Park Comprehensive Cancer Center US
• Trinity Health Oakland Hospital US
• New Mexico Cancer Center US
• Thomas Jefferson University US
• New York Hospital Queens US
• The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute US
• University of Cincinnati US
• Valley Health System US
• Trinity Health US
• St. Vincent Hospital US
• Florida College US
• Trinity Health Ann Arbor Hospital US
• Moffitt Cancer Center US
• Mount Sinai Medical Center US
• The Ohio State University US
• The University of Texas Southwestern Medical Center US
• Sidney Kimmel Cancer Center US
• Oklahoma Cancer Specialists and Research Institute US
• Miami Valley Hospital South US
• University of California, San Francisco US
• Mayo Clinic in Arizona US
• University of Florida Health US

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