A Pilot Phase II Study of Neoadjuvant Fulvestrant plus Abemaciclib in Women with Advanced Low--Grade Serous Carcinoma

Methods

Women with untreated, unresectable stage III or IV LGSOC were eligible. Patients received fulvestrant (500 mg IM on day 1 and 15 of the first 28-day cycle, then day 1 of subsequent cycles) and abemaciclib 150 mg orally BID. Pre/perimenopausal patients received goserelin 10.8 mg subcutaneously every 12 weeks for ovarian suppression.

Imaging re-assessment was performed every 8 weeks using RECIST 1.1 until deemed resectable. Following interval cytoreductive surgery (ICS), patients received 4 cycles of adjuvant fulvestrant and abemaciclib followed by maintenance letrozole. Patients with progressive disease were removed from the study and received standard chemotherapy.

The pPrimary endpoint is best overall response clinical benefit rate (BOR CBR). Results: Fifteen patients were enrolled and evaluable for efficacy. BOR CBR in the neoadjuvant setting was 100%, with (9/15 patients (60%) achieving partial response (PR), and 6/15 patients (40%) showing stable disease (SD).

One patient with radiologic PR had pathologic complete response at ICS. Nine of fifteen patients (60%) underwent ICS – 5 (55.5%) with complete gross resection, 2 (22.2%) with <1cm residual disease, and 2 (22.2%) with suboptimal cytoreduction. Median time on study prior to surgery was 8.38 months.

Conclusion: Neoadjuvant treatment with fulvestrant and abemaciclib was tolerable and demonstrated unprecedented response and CBGR rates in this pilot study. These results compare favorably withto published outcomes of neoadjuvant chemotherapy in LGSOC.