A pilot phase II study of neoadjuvant fulvestrant plus abemaciclib in women with advanced low-grade serous carcinoma.
Authors: Cobb Lauren P. , Davis Joseph , Hull Sara , Vining David J. , Fellman Bryan M. , Yuan Ying , Westin Shannon Neville , Taylor Jolyn Sharpe , Bevers Michael W. , Shafer Aaron , Fleming Nicole D. , Lu Karen H. , Gershenson David Marc , Jazaeri Amir A. 
Published: June 2022

5522 Background: Neoadjuvant chemotherapy has demonstrated limited activity in low-grade serous carcinomas (LGSOC) of the ovary, fallopian tube, and peritoneum, with objective response rate of 11% and complete gross resection (CGR) rate of 38% at the time of interval cytoreductive surgery (ICS). LGSOC has many similarities to hormone receptor positive (HR+) breast cancer, including clinical benefit from endocrine therapies in the recurrent and maintenance settings. Based on the activity of antiestrogen plus CDK4/6 inhibitor combination therapy in HR+ breast cancer, we conducted a phase II pilot study to assess the clinical benefit of neoadjuvant treatment with fulvestrant and abemaciclib for women with advanced LGSOC. Methods: Women with unresectable, untreated stage III or IV LGSOC of the ovary, fallopian tube or peritoneum were eligible. Patients received fulvestrant (500 mg IM on day 1 and 15 of the first 28-day cycle, followed by day 1 of subsequent cycles) and abemaciclib 150 mg orally BID. Pre/perimenopausal patients also received goserelin 10.8 mg subcutaneously every 12 weeks for ovarian suppression. Patients continued treatment until deemed resectable by the treating surgeon with imaging re-assessment every 8 weeks using RECIST 1.1. Following ICS, patients receive 4 cycles of adjuvant fulvestrant and abemaciclib and then transition to maintenance letrozole. Patients with progressive disease (PD) were removed from study and received standard of care chemotherapy. Primary endpoint is clinical benefit rate (CBR). Results: Fifteen patients were enrolled and evaluable. At data cutoff date (January 20, 2022), 7 of 15 patients (47%) had partial response (PR) (one patient with radiologic PR had a pathologic complete response at ICS), 5 of 15 (33%) had stable disease (SD), and 3 of 15 (20%) had progressive disease (PD), resulting in a CBR of 80%. Of the 7 patients with PR, 3 have had ICS with CGR, 3 have not yet had ICS, and 1 underwent resection of supraclavicular disease with small volume residual disease in the chest. Of the 5 patients with SD, one underwent ICS with CGR, and two have been on treatment for 8 and 16 weeks with reduction in measurable disease but not yet deemed to be candidates for surgery. Four of the 5 patients (80%) who had ICS, had CGR. Median time on study prior to surgery was 24 weeks. Adverse events (grade 3 or 4) possibly related to abemaciclib occurred in 2 patients (13.3%) and included acute kidney injury (6.7%) and neutropenia (6.7%). Conclusions: Neoadjuvant treatment with fulvestrant and abemaciclib was tolerable and demonstrated unprecedented response and CGR rates in this pilot study. These results compare favorably to published outcomes of neoadjuvant chemotherapy in LGSOC. Further studies are planned to explore this new treatment option in a larger study population. Clinical trial information: NCT03531645.