Neoadjuvant talazoparib in patients with germline BRCA1/2 (gBRCA1/2) mutation-positive, early HER2-negative breast cancer (BC): Results of a phase 2 study.

505 Background: Talazoparib (TALA) is a poly(ADP-ribose) polymerase inhibitor approved as monotherapy for treating adult patients (pts) with g BRCA1/2-mutated HER2-negative locally advanced or metastatic BC. Methods: This phase 2, non-randomized, single-arm, open-label study (NCT03499353) evaluated the efficacy and safety of TALA in the neoadjuvant setting for pts with early g BRCA1/2-mutated HER2− BC. Primary endpoint was evaluation of pathologic complete response (pCR) as assessed by Independent Central Review (ICR) after completing 24 weeks of neoadjuvant TALA monotherapy 1 mg QD (0.75 mg for moderate renal impairment) followed by surgery. Secondary endpoints included pCR by investigator (INV) and residual cancer burden (RCB) by ICR (RCB: 0 [pCR], I [minimal], II [moderate], III [extensive]). The evaluable population included pts who received at least 80% of the TALA dose prescribed at treatment start and underwent breast surgery and pCR assessment, plus those who progressed before pCR could be assessed. The intent-to-treat (ITT) population included all pts who received at least 1 dose of TALA. Results: Of 61 pts treated with TALA (ITT and safety populations), 48 comprised the evaluable population. All pts had triple-negative BC. 60 pts had adenocarcinoma and 1 had squamous cell histology, with the following staging: I=20, II=27, III=14. Mean age was 44.6 years, mean duration of 4.5 wks since disease onset, mean duration of treatment of 23.3 wks, and mean overall relative dose intensity of 84.5% (ITT population). pCR (assessed by ICR and INV) and RCB (by ICR) for the evaluable and ITT populations are shown in the table below. Ten (16.4%) patients discontinued treatment due to progressive disease. One pt had a disruption of treatment as a result of COVID-19 restrictions, 2 pts for other reasons: to undergo surgery early and consent withdrawal; 9 patients received <80% dose. Treatment-emergent adverse events (AEs) were reported in 98.4% of pts (27.9% grade [G] 1, 23.0% G2, 45.9% G3, 1.6% G4); the most common were fatigue (78.7%; G1 54.1%; G2 21.3%; G3 3.3%), nausea (68.9%; G1 54.1%; G2 13.1%; G3 1.6%), and alopecia (57.4%; G1 54.1%; G2 3.3%). Three (4.9%) pts discontinued treatment due to AEs (G3 anemia [n=2] and G3 vertigo [n=1]) and continued on study. Conclusions: TALA monotherapy in the neoadjuvant setting was active and showed pCR rates comparable to those observed with combination anthracycline and taxane-based chemotherapy regimens and was generally well tolerated. Clinical trial information: NCT03499353. [Table: see text]