Ribociclib-Letrozole Regimen Tested in Ovarian, Endometrial Cancer

A phase II study found that the combination of ribociclib and letrozole showed promising activity in patients with estrogen receptor-positive ovarian cancer and endometrial cancer. The most benefit was observed in low-grade serous ovarian cancers.

“Up to 60% of ovarian tumors can be estrogen receptor (ER)-positive,” said Gerardo Colon-Otero, MD, of the Mayo Clinic in Jacksonville, Florida.

Previous trials of aromatase inhibitors in ovarian and endometrial cancer have been disappointing, but recent work showing good results when combined with cyclin kinase inhibitors, such as ribociclib, led to the new trial. Colon-Otero presented results of the study at the American Society of Clinical Oncology (ASCO) 2019 Annual Meeting, held May 31-June 4 in Chicago (Abstract 5510).

The phase II trial included 20 women with ER-positive ovarian cancer and 20 with ER-positive endometrial cancer. All patients received letrozole 2.5 mg daily and ribociclib 400 mg daily; they were treated until progression or unacceptable toxicity.

The median age in the ovarian cancer cohort was 61 years; in the endometrial cancer cohort, it was 64.5 years. Most patients in both cohorts had a performance status of 0, and most of the cohorts were white. Ovarian cancer patients had a median of three previous chemotherapy regimens; for those with endometrial cancer, the median was two previous regimens.

The study’s primary endpoint was met, based on the percentage of patients still alive and progression-free after 12 weeks (PFS12). The PFS12 in the ovarian cancer cohort was 50%, and 25% (five patients) were progression-free at 23 weeks. In the endometrial cancer patients, the PFS12 rate was 55%, and 45% were progression-free at 23 weeks.

Patients with low-grade serous ovarian cancer appeared to derive the most benefit, as all three patients were progression-free for at least 23 weeks; in fact, those three patients remained on therapy for more than 28, 24, and 19 months, respectively. Only 2 of the other 17 patients (12%) with ovarian cancer were progression-free at 23 weeks.

In the endometrial cancer patients, the most benefit was seen in those with grade 1–2 disease; 64% of those patients were progression-free for at least 23 weeks, compared with 22% of those with grade 3 disease.

The median PFS was 2.8 months in the ovarian cancer cohort, and 5.4 months in the endometrial cancer patients. The median overall survival in the two cohorts was 18.9 months and 15.7 months, respectively.

The most common treatment-related serious adverse events (AEs) included leukopenia (17.5%), neutropenia (15%), lymphopenia (7.5%), liver enzyme elevations (7.5%), and fatigue (5%). These were grade 3 AEs, with the exception of one case of grade 4 lymphopenia. There were no grade 5 AEs.

“Additional studies of this combination are indicated in ER-positive low-grade serous ovarian cancer, and grade one and two endometrial cancers,” Colon-Otero concluded.

Helen Mackay, MD, of the Princess Margaret Cancer Center in Toronto, discussed the study for ASCO. She agreed that these are “interesting data” and that larger, randomized trials are warranted. She noted, though, that some outstanding questions about the approach remain.

“Are the aromatase inhibitors the same in endocrine and gynecologic cancers as in breast?” she asked. “What’s going on in these pathways?... I’d encourage people to address the fundamental questions before moving into toxic combinations.”