TY - JOUR
T1 - Efficacy and safety of first-line veliparib and carboplatin–paclitaxel in patients with HER2− advanced germline BRCA+ breast cancer
T2 - Subgroup analysis of a randomised clinical trial
AU - Arun, Banu K.
AU - Han, Hyo S.
AU - Kaufman, Bella
AU - Wildiers, Hans
AU - Friedlander, Michael
AU - Ayoub, Jean Pierre
AU - Puhalla, Shannon L.
AU - Bell-McGuinn, Katherine M.
AU - Bach, Bruce A.
AU - Kundu, Madan G.
AU - Ratajczak, Christine K.
AU - Maag, David
AU - Diéras, Véronique
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/9
Y1 - 2021/9
N2 - Background: Addition of veliparib to carboplatin–paclitaxel, with continuation of veliparib monotherapy if carboplatin–paclitaxel was discontinued, improved progression-free survival (PFS) in patients with germline BRCA-associated locally advanced/metastatic HER2− breast cancer and ≤2 lines of previous cytotoxic therapy for metastatic disease in BROCADE3. A pre-planned subgroup analysis evaluated efficacy and safety in patients without previous cytotoxic therapy for metastatic disease. Methods: Patients were randomised 2:1 to receive veliparib (120 mg orally BID) or placebo on days −2 to 5. Carboplatin (AUC 6) was administered on day 1, and paclitaxel (80 mg/m2) on days 1, 8 and 15 (21-day cycles). Patients discontinuing carboplatin–paclitaxel for reasons besides progression could continue veliparib/placebo monotherapy (300 mg BID, increasing to 400 mg BID if tolerated) until progression. The primary end-point was PFS assessed by investigator. Results: Of 509 patients in the intention-to-treat population (98.6% female; mean age 47, standard deviation 11), 413 (81%) had no previous cytotoxic therapy for metastatic disease (274, veliparib; 139, placebo). In the first-line subgroup, median PFS was 16.6 months (95% confidence interval [CI] 13.4–18.7) versus 13.1 months (95% CI 11.4–14.5) for the veliparib versus control groups (hazard ratio 0.70, 95% CI 0.54–0.89, P = .004). More patients were alive and progression-free at 2 years (36% versus 23.2%) and 3 years (27.9% versus 13.3%) in the veliparib versus control group. Adverse events unrelated to progression leading to study drug discontinuation occurred in 25 (9.1%) and 8 (5.8%) patients. Conclusions: Veliparib with carboplatin–paclitaxel led to durable disease control among first-line patients, suggesting a benefit of this treatment approach in early lines. Clinical trial registration: NCT02163694.
AB - Background: Addition of veliparib to carboplatin–paclitaxel, with continuation of veliparib monotherapy if carboplatin–paclitaxel was discontinued, improved progression-free survival (PFS) in patients with germline BRCA-associated locally advanced/metastatic HER2− breast cancer and ≤2 lines of previous cytotoxic therapy for metastatic disease in BROCADE3. A pre-planned subgroup analysis evaluated efficacy and safety in patients without previous cytotoxic therapy for metastatic disease. Methods: Patients were randomised 2:1 to receive veliparib (120 mg orally BID) or placebo on days −2 to 5. Carboplatin (AUC 6) was administered on day 1, and paclitaxel (80 mg/m2) on days 1, 8 and 15 (21-day cycles). Patients discontinuing carboplatin–paclitaxel for reasons besides progression could continue veliparib/placebo monotherapy (300 mg BID, increasing to 400 mg BID if tolerated) until progression. The primary end-point was PFS assessed by investigator. Results: Of 509 patients in the intention-to-treat population (98.6% female; mean age 47, standard deviation 11), 413 (81%) had no previous cytotoxic therapy for metastatic disease (274, veliparib; 139, placebo). In the first-line subgroup, median PFS was 16.6 months (95% confidence interval [CI] 13.4–18.7) versus 13.1 months (95% CI 11.4–14.5) for the veliparib versus control groups (hazard ratio 0.70, 95% CI 0.54–0.89, P = .004). More patients were alive and progression-free at 2 years (36% versus 23.2%) and 3 years (27.9% versus 13.3%) in the veliparib versus control group. Adverse events unrelated to progression leading to study drug discontinuation occurred in 25 (9.1%) and 8 (5.8%) patients. Conclusions: Veliparib with carboplatin–paclitaxel led to durable disease control among first-line patients, suggesting a benefit of this treatment approach in early lines. Clinical trial registration: NCT02163694.
KW - BRCA
KW - Breast cancer
KW - Chemotherapy
KW - PARP inhibitor
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UR - http://www.scopus.com/inward/citedby.url?scp=85109194900&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2021.05.037
DO - 10.1016/j.ejca.2021.05.037
M3 - Article
C2 - 34243076
AN - SCOPUS:85109194900
SN - 0959-8049
VL - 154
SP - 35
EP - 45
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -