Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatin in patients with HER2-negative BC and HRD -long-term survival of the GeparOLA study.

Backgound: The GeparOLA study evaluated paclitaxel(P) plus olaparib(O) in neoadjuvant chemotherapy (NACT) for patients with HER2-negative early breast cancer (eBC) with homologous recombination deficiency (HRD). HRD was defined by high HRD-score or germline(g)/tumor(t) BRCA1/2 mutations (g/tBRCA1/2mut). Here, we report long-term outcome data.

Patients and methods: GeparOLA (NCT02789332) was a randomized, multicenter, prospective, open-label, phase II trial. Patients with HER2-negative eBC, HRD, indication for chemotherapy (cT2-cT4a-d or cT1c and cN+ or cT1c and pNSLN+ or cT1c and triple-negative[TN]BC or cT1c and Ki-67>20%), were randomly assigned to P+O or P+carboplatin(Cb), both followed by epirubicin+cyclophosphamide(EC). Long-term efficacy endpoints were secondary endpoints and included invasive disease-free survival(iDFS), distant disease-free survival(DDFS) and overall survival(OS).

Results: Between 09/2016 and 07/2018, 107 patients were randomized and 106 (PO N=69;PCb N=37) started treatment. The median age was 47.0 years; 35.8% had cT1 tumors; 31.4% were cN+; 86.8% had G3 tumors; 89.6% had Ki-67>20% and 72.6% were TN. After median follow-up of 49.8 months, 18(15 PO; 3 PCb) iDFS events and 7(6 PO; 1 PCb) deaths were reported. The 4-year iDFS (76.0%PO vs 88.5%PCb, HR=2.86 [95%CI 0.83-9.90],log-rank p=0.081), DDFS (81.2%PO vs 93.4%PCb, HR=3.03 [95%CI 0.67-13.67],log-rank p=0.129) and OS (89.2%PO vs 96.9%PCb, HR=3.27 [95%CI 0.39-27.20],log-rank p=0.244) tended to be inferior with O. Patients without g/tBRCA1/2mut benefited from Cb [7/30 patients had iDFS/DDFS events in PO vs 0/16 in PCb].

Conclusion: For HER2-negative eBC with HRD, olaparib showed a tendency for inferior outcomes compared to carboplatin, particularly in patients without g/tBRCA1/2mut. In patients with g/tBRCA1/2mut olaparib may replace carboplatin.