In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 18_suppl ( 2021-06-20), p. LBA1-LBA1
Kurzfassung:
LBA1 Background: PARP inhibitors (PARPi) target cancers with homologous recombination repair defects by synthetic lethality. The PARPi olaparib (OL) is licensed for metastatic HER2-negative breast cancer with BRCA1/2 germline mutation (gBRCAm). Despite (neo)adjuvant chemotherapy ([N]ACT), recurrence rates in patients (pts) with gBRCAm early breast c ancer (EBC) can be high. Novel adjuvant treatments are needed. Methods: OlympiA (NCT02032823), a randomized, double-blind, phase III study, enrolled pts with gBRCAm and HER2-negative (TNBC or hormone-receptor+ [HR+]) high-risk EBC after primary local treatment and ACT/NACT. Eligible pts with TNBC had ≥pT2 or ≥pN1 disease prior to ACT or non-pCR after NACT; those with HR+ BC had ≥4 positive nodes prior to ACT or non-pCR and CPS & EG score ≥3 after NACT. Pts were randomized 1:1 to 1 year of continuous oral OL (300 mg BID) or placebo (PL). Endocrine therapy and bisphosphonates were allowed. The primary endpoint was invasive disease-free survival (IDFS) in the ITT population. Secondary endpoints included distant DFS (DDFS), overall survival (OS) and safety. Safety analysis included adverse events of special interest (AESI) (myelodysplastic syndrome/ acute myeloid leukemia, new primary malignancy, pneumonitis). Per protocol IDMC interim analysis (IA) review was triggered at 165 IDFS events in the first 900 pts, with superiority boundaries based on a hierarchical multiple testing procedure: P 〈 0.005 for IDFS, followed by P 〈 0.005 for DDFS and p 〈 0.01 for OS. Results: 1836 pts were enrolled between 06/14–05/19; 49.9% had ACT, 50.1% NACT. Baseline demographics and tumor characteristics were balanced between arms. 82.2% had TNBC; 26.5% received a platinum agent. The IDMC recommended data unblinding as IA showed a significant benefit of OL vs PL for IDFS (hazard ratio [HR] 0.58; 99.5% CI 0.41, 0.82; P 〈 0.0001) at 2.5 yrs median follow-up. IDFS events occurred in 106/921 and 178/915 pts assigned to OL and PL, respectively. 3-yr IDFS was 85.9% vs 77.1% (diff. 8.8%; 95% CI 4.5%, 13.0%). DDFS was significantly improved with OL (HR 0.57; 99.5% CI 0.39, 0.83; P 〈 0.0001); 3-yr DDFS was 87.5% vs 80.4% (diff. 7.1%; 95% CI 3.0%, 11.1%). OS was greater for OL than PL but was not statistically significant at IA (HR 0.68; 99.0% CI 0.44, 1.05; P = 0.024); 3-yr OS% 92.0% vs 88.3% (diff. 3.7%; 95% CI 0.3%, 7.1%). Median intended OL exposure was 94.8%. AEs were consistent with the label. G3+ AEs in 〉 1% of OL pts were; anemia (8.7%), neutropenia (4.8%), leukopenia (3.0%), fatigue (1.8%), and lymphocytopenia (1.2%). SAEs and AESI were not increased by OL, SAE 8.7% vs 8.4% and AESI 3.3% vs 5.1%, OL vs PL respectively. Conclusions: Adjuvant OL following ACT or NACT significantly improved IDFS and DDFS with acceptable toxicity in pts with gBRCAm and high-risk HER2-negative EBC. Clinical trial information: NCT02032823.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2021.39.15_suppl.LBA1
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2021
ZDB Id:
2005181-5
