A case series of four patients with recurrent ovarian granulosa cell tumors treated with CDK4/6 inhibitors and estrogen blockade in a pilot study

Background: No optimal management strategy has been established for advanced and recurrent granulosa cell tumors. This presents a clinical challenge as viable treatment options are limited. Considering their efficacy in hormone receptor positive breast cancer, addition of cyclin dependent kinase 4/6 (CDK4/6) inhibitors may benefit patients burdened with other HR+ (hormone receptor) cancers. CDK4/6 inhibitors work synergistically with estrogen blockade and can help overcome estrogen blockade resistance. We report a case series of four patients with GCTs (Granulosa cell tumors) treated with CDK4/6 inhibition in combination with hormonal therapy. Our objective is to report the clinical outcomes of patients treated with this novel combination. Cases: A retrospective review of four patients diagnosed with relapsed GCTs treated with a CDK4/6 inhibitor in combination with estrogen blockade was performed. Patient clinical data was collected from the electronic medical records of a large academic institution. All patients had adult-type GCTs. Median age at initial diagnosis was 42.5 years (range 27–73 years). All tumor samples had a forkhead box L2 (FOXL2) and telomerase reverse transcriptase (TERT) genetic alteration on testing. Patients had a median of five recurrences or progressions prior to the treatment of interest (range 4–8). Median time on treatment was 38 months (range 6–60 months). At last follow-up, one patient was still on treatment without disease, two patients had meaningful duration of response spanning over a year but ultimately progressed, and one patient had progressive disease on this treatment. Treatment was well tolerated. No patients discontinued treatment due to toxicity. Conclusion: GCT patients treated with CDK4/6 inhibition plus estrogen blockade had durable responses from treatment and the therapy was well tolerated. These findings indicate that the combination of CDK4/6 inhibitors with estrogen blockade could provide a promising therapeutic option for patients with recurrent ovarian GCTs, highlighting the need for further investigation through prospective clinical trials.

Granulosa cell tumor; CDK4/6 inhibitor; Hormone therapy; Ovarian cancer; Palbociclib

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