Neoadjuvant giredestrant + palbociclib (P) vs. anastrozole (A) + P in postmenopausal women with estrogen receptor-positive, HER2-negative, untreated early breast cancer (ER+, HER2– eBC): Patient (pt)-reported outcomes (PROs) in the randomized, open-label, international phase II coopERA BC study.

Abstract

591 Background: Endocrine therapies (ETs) are the therapeutic mainstay for ER+ BC but persistent adverse events (AEs; eg joint pain, especially with aromatase inhibitors) negatively impact quality of life, and resistance impacts efficacy. Giredestrant, a highly potent, nonsteroidal, oral selective ER antagonist and degrader (PO SERD), may help address these issues. coopERA BC (NCT04436744) evaluated giredestrant in eBC and met its primary endpoint, demonstrating a greater reduction of Ki67 with giredestrant vs. A after 2 weeks. Giredestrant was well tolerated as a single agent and with P. We report exploratory PRO analyses. Methods: Pts with cT1c-cT4a-c (≥ 1.5 cm within cT1c) ER+, HER2– untreated eBC and baseline Ki67 score ≥ 5% were randomized 1:1 to 30 mg PO daily (QD) giredestrant or 1 mg PO QD A on days (D)1–14 of a window-of-opportunity phase. A 16-week neoadjuvant phase added 125 mg PO QD P on D1–21 of four 28-D cycles. Presence/frequency/severity/interference of relevant symptomatic AEs were assessed at Cycles 1–4 via NCI PRO-CTCAE library items; overall burden due to AEs, via FACT-G item GP5. Results: PRO completion rates were > 80% at all time points. PRO-CTCAE postbaseline frequency scores were comparable between arms and mostly 0/1 (never/rare; reported for: Diarrhea > 80% of pts; hot flash > 60%; joint pain > 65%; nausea > 90%; vomiting > 90%). No rash was reported by > 90% of pts; fatigue at 0/1 severity (none/mild) by > 75% and at 0/1 interference (none at all/a little bit) by 80%. Hot flash frequency scores of 2–4 (occasionally/frequently/almost constantly) were reported by 30% of pts in the giredestrant + P arm and 37% in the A + P arm; joint pain frequency scores of 2–4, by 25% and 35%. Worst postbaseline scores of 3–4 are shown in the table. FACT-G GP5 showed greater proportions of “improved/no change” responses in the giredestrant + P than the A + P arm at Cycles 2–4 (Cycle 2 75%; Cycle 3 71%; Cycle 4 68% vs. 62%; 66%; 53%), and smaller proportions of “worsened” responses (25%; 29%; 32% vs. 38%; 34%; 47%). Conclusions: This is the first analysis to our knowledge of PROs with a PO SERD in eBC; it showed that most pts reported minimal symptomatic AEs at frequency and severity levels that were generally numerically lower in the giredestrant + P than the A + P arm (particularly joint pain). Furthermore, there were numeric trends towards greater stability and improvement and less worsening of treatment burden in the giredestrant + P arm. Studies to further assess giredestrant’s clinical benefit are ongoing in the adjuvant setting. Clinical trial information: NCT04436744 . [Table: see text]