K. Jhaveri
Jun 26, 2021
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Influential Citations
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Journal
The oncologist
Abstract
Giredestrant is an oral, non-steroidal, selective ER antagonist with promising single-agent activity. Komal L. Jhaveri, M.D., of Memorial Sloan Kettering Cancer Center, presented findings from a phase I trial of giredestrant in 111 patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer [1]. All patients had breast cancer that progressed while receiving endocrine therapy in the adjuvant setting for at least 24 months and/or in the advanced setting for at least 6 months. Prior therapies included a CDK4/6 inhibitor (64%), fulvestrant (21%), and/or chemotherapy for metastatic disease (16%). The median patient age was 58 years and 65% of patients had visceral disease at baseline. Nearly half of patients (47%) had an ESR1 mutation. Patients were assigned to treatment with giredestrant across 4 dose cohorts: 10 mg (n = 6), 30 mg (n = 41), 90/100 mg (n = 55), and 250 mg (n = 9). Giredestrant exhibited antitumor activity across all dose cohorts and patient subgroups, regardless of ESR1 mutation status or prior treatment with CDK4/6 inhibitors, fulvestrant, or chemotherapy. The overall response rate (ORR) among patients treated with giredestrant 30 mg was 55%. Treatment with giredestrant was well tolerated; the maximum tolerated dose was not reached. The most common adverse events (AEs) of any grade were fatigue, arthralgia, back pain, nausea, and diarrhea. Grade 1–2 sinus bradycardia was observed in 9 patients. Based on promising phase I findings, giredestrant 30 mg is currently undergoing additional evaluation in randomized phase II and III trials as a single agent and in combination with CDK4/6 inhibitors in patients with ER-positive breast cancer.