TAMPA, Fla. — About a fourth of patients with recurrent low-grade serous ovarian cancer (LGSOC) obtained durable responses to the combination of CDK4/6 inhibitor ribociclib (Kisqali) and letrozole, a small single-arm trial showed.

Overall, 23% of 48 patients had partial responses, increasing to 26% in those who had baseline and confirmatory CT scans. Almost 80% obtained clinical benefit. Median duration of response was 19.1 months.

Aside from decreased neutrophil count, grade 3+ adverse events (AEs) were uncommon, reported Brian Slomovitz, MD, of Mount Sinai Medical Center in Miami, at the Society of Gynecologic Oncology meeting.

“Ribociclib and letrozole is an active combination in patients with low-grade serious ovarian cancer,” he said. “The overall response rate [ORR], progression-free survival [PFS], and duration of response [DOR] compare favorably to the most active agents that have previously been investigated. The adverse event profile is as expected.”

“We did collect pretreatment specimens, so an evaluation of translational endpoints will be performed. Developing a strategy for FDA approval is also warranted,” he added.

LGSOC accounts for 5%-10% of all serous ovarian cancers. The disease is associated with prolonged survival, but more than 80% of patients have recurrences. From 95%-100% of LGSOCs are estrogen-receptor positive. Patients ages 35 or younger have worse prognosis, but the tumors have demonstrated responsiveness to endocrine therapies in multiple clinical settings (adjuvant, neoadjuvant, maintenance, recurrence), said Slomovitz.

Clinical studies have shown that 14% of recurrent LGSOCs respond to aromatase inhibitors, but are less sensitive to other types of endocrine therapy. Chemotherapy produces responses in 0%-15% of LGSOC. Studies of bevacizumab (Avastin) have shown response rates of 40%-47%, usually in combination with chemotherapy, and more recently, MEK inhibitors have demonstrated response rates of about 25%, said Slomovitz.

The rationale for treating LGSOC with a CDK4/6 inhibitor and endocrine therapy includes copy-number variant studies showing frequent loss of chromosome 9p in the region that contains CDKN2A, which encodes for p16. Other studies have shown that expression of p16 and retinoblastoma determines ovarian cancer response to CDK4/6 inhibition. Two-thirds of patients with LGSOC absence of p16 expression, and loss of p16 could be a predictive marker for response to CDK4/6 inhibition.

Slomovitz reported findings from an open-label, single-arm trial involving 51 patients with recurrent LGSOC. All patients received ribociclib and letrozole for 3 weeks of a 28-day cycle. Treatment continued until disease progression. Laboratory and radiographic assessments occurred after every three cycles of therapy.

The primary endpoint was ORR, and secondary endpoints included clinical benefit rate (CBR), PFS, overall survival (OS), DOR, and AEs. An ORR ≤10% indicated ineffective treatment.

Of the 51 patients enrolled, 48 were included in the data analysis. The patients had a mean age of 58.5. About three-fourths had received prior chemotherapy, on- fourth prior hormonal therapy, and 13% prior immunotherapy.

The results showed that 11 of the 48 patients had partial responses to ribociclib and letrozole, increasing to 11 of 42 when the analysis was limited to patients who had confirmatory CT scans. Slomovitz said 38 of 48 (79%) patients obtained clinical benefit from the treatment, 90% in those with pretreatment and posttreatment CT scans. Median time to response was 7.9 months.

Two-thirds of the 42 patients with confirmatory CT scans had some degree of tumor shrinkage. The cohort had a median PFS of 19.1 months, and median OS had yet to be reached.

The most common AE (all grade and grade 3+) was decreased neutrophil count (63%, 44%). Other AEs included decreased white blood cell count (46%), anemia (42%), nausea (42%), decreased lymphocytes (21%), anorexia (19%), myalgia (13%), and weight loss (11%). No other AE reached grade 3+ severity in more than 8% of patients.

Comparing the results with studies of other therapies for LGSOC, Slomovitz noted that ribociclib-letrozole led to the longest PFS reported to date (7.2-13.0 months for other regimens). The 19.1-month median DOR also exceeded all the other alternative therapies (5.9-13.6 months). The response rate compared favorably with reported rates from other trials (6%-26%), as did the CBR (79% vs 64%-85%).

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