LBA1 Denosumab added to 2 different nab-paclitaxel regimens as neoadjuvant therapy in patients with primary breast cancer: Time to event analysis from the GeparX 2 × 2 randomized clinical trial

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GeparX (NCT02682693) investigated denosumab (Dmab) alongside anthracycline/taxane-based neoadjuvant chemotherapy (NACT) and two different nab-paclitaxel (nabP) schedules. Weekly nabP showed higher pathological complete response (pCR) rates, while adding Dmab did not. Patients (pts; n=780) were randomized in a 2x2 fashion to either receive Dmab (120 mg s.c. q4w for 6 cycles) or none and to receive nabP (125 mg/m2) either weekly or d1+8 q3w each for 12 weeks. Pts with TNBC received additional carboplatin, and pts with HER2+ BC received trastuzumab biosimilar ABP980 for 8 cycles and pertuzumab for at least 4 cycles. All pts subsequently received standard epirubicin/cyclophosphamide for 4 cycles. This is the preplanned analysis of invasive disease-free survival (iDFS), distant disease-free survival (DDFS) and overall survival (OS). After a median follow-up of 62.3 months, no significant difference in iDFS was observed between pts receiving Dmab or none (HR= 0.87, 95% CI 0.62–1.21; p=0.39) or between different nabP schedules (HR= 0.87, 95% CI 0.62–1.21; p=0.41). Pts receiving Dmab had numerically longer DDFS although not reaching statistical significance with a HR of 0.77 (CI 0.54, 1.1) p=0.16 and an estimated 5y DDFS of 85.8% with vs 80.2% without Dmab. A trend for a higher DDFS with vs without Dmab in the pCR group HR 0.46 (CI 0.21, 1.01) p=0.054 also did not reach significance. No significant differences in OS between pts receiving or not receiving Dmab or between different nabP schedules were detected. Overall, absence of pCR at surgery was associated with a poorer outcome with 5y rates for iDFS 73.9% vs 87.8%, DDFS 76.1% vs 91.6% and OS 86.2% vs 95.4% in pts without vs with pCR. No unexpected long-term toxicities were noted. This is the first randomized trial to report long-term outcomes for the addition of Dmab to anthracycline/taxane-based neoadjuvant therapy. Although there were numerically less distant relapses with Dmab, this did not reach statistical significance. Despite the observed increase in pCR with nabP weekly, this did not translate into an improved long-term outcome.

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