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Cisplatin with or without rucaparib after preoperative chemotherapy in patients with triple-negative breast cancer (TNBC): Hoosier Oncology Group BRE09-146.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: Patients (pts) with triple negative breast cancer (TNBC) who have residual disease after preoperative chemotherapy have a high risk of recurrence. No standard systemic therapy has proven benefit. Data suggest that some pts with TNBC and/or BRCA mutations may be sensitive to DNA-damaging chemotherapy and PARP inhibition. Methods: Eligible pts with TNBC or known BRCA mutations who had residual lymph node involvement or > 2 cm invasive disease after anthracycline or taxane neoadjuvant therapy were assigned 1:1 to postoperative cisplatin (C: 75 mg/m2D1 q3 wks x 4) +/- rucaparib (R: 24-30 mg IV D1,2,3 q3 wks x 4 followed by rucaparib 30 mg IV or 100 mg orally wkly for 24 wks). BROCA analysis (U. Washington) was used to identify deleterious germline mutations. The primary objective is 2-yr DFS. Results: 128 pts were enrolled. Median age was 48; 6 pts were known at study entry to have BRCA1 or BRCA2 mutations. Neoadjuvant therapy included anthracyclines in 57% and taxanes in 91%. Median tumor size at surgery was 1.9 cm (0-11.5) with median LN involvement 1 (0-38); Toxicity required C dose reduction (20% of pts) or delay (~43% of pts) in both arms. R dose reduction was uncommon (6%). Overall 73% of pts completed planned C. With a median follow-up of 9 months, 1-yr DFS was similar (~76%) in both treatment groups. BROCA identified deleterious mutations in 22/101 (22%) pts (8 BRCA 1, 12 BRCA 2, 2 BRIP1). 1-yr DFS in the 22 pts with mutations was ~85% compared to 79% without mutations. Whole transcriptome sequencing of paired pre vs. post preoperative chemotherapysamples will be reported separately (Radovich et al, ASCO 2014). Conclusions: The addition of low dose rucaparib (current phase II monotherapy dose 600 mg orally twice daily) did not impact the toxicity of cisplatin or improve 1-yr DFS. Comparison to predicted DFS based on residual cancer burden (RCB) is planned to investigate potential benefit from cisplatin. Genetic testing was underutilized in this high risk population with only 30% of BRCA1 and BRCA2 mutations identified as part of routine clinical care. Clinical trial information: NCT01074970.