Abstract P2-16-03: Neoadjuvant treatment of triple negative breast cancer patients with docetaxel and carboplatin to assess anti-tumor activity

Background: Anthracycline- and taxane-based neoadjuvant chemotherapy (NAT) in triple negative breast cancer (TNBC) patients yields a pathological complete response (pCR) rate of approximately 45%. Anthracyclines can lead to long-term toxicities including congestive heart failure and leukemia. TNBC patients achieving pCR have excellent long-term outcomes irrespective of NAT regimen. This study was designed to evaluate the efficacy of a non-anthracycline NAT regimen with carboplatin and docetaxel in TNBC. Correlative studies include detecting and tracking plasma circulating tumor DNA (ctDNA) to determine if it will predict clinical outcomes, and whole exome sequencing (WES) on tissue samples to decipher the genomic architecture of those who achieve pCR versus those who do not. Methods: This is a joint analysis of two identical multicenter trials. Eligible patients with AJCC 7 clinical stages II and III TNBC received docetaxel 75mg/m2 and carboplatin AUC 6 every 3 weeks X 6 cycles. Following NAT, all patients underwent definitive surgery. The primary endpoint is pCR (no invasive tumor in the breast and axilla). Secondary objectives include evaluating ctDNA as a prognostic biomarker that may be used in identifying TNBC patients at a high risk of disease relapse, and evaluating differences in the genomic architecture between pCR and non-pCR patients. Patients have a research biopsy at baseline, cycle 1 day 3 (optional), and at definitive surgery for those with residual disease. Plasma for ctDNA is collected at baseline, cycle 1 day 3, at definitive surgery, and every 6 months for 5 years. Results: Between 2014 and 2019, 103 patients have been registered. Median age is 53 years (range 25-74), 27.2%: African-American, 77.7%: clinical stage II. Ninety-nine have completed NAT and have had surgery. In the intent to treat population, the preliminary pCR rate is 46.5% (95% CI 36.9% - 56.2%). Nine (8.7%) have developed recurrent disease, and 7 (6.8%) have died. Preliminary ctDNA results from 6 patients (4 non-pCR, 2 pCR) show that ctDNA is detectable in 67%. We identified 627 somatic variants by exome analysis. Of these, 10 variants overlapped with the Swift panel (Accel-Amplicon™ 56G Oncology Panel v2) used for ctDNA sequencing and variant detection. TP53 variants were identified in all 6 patients’ tumor tissue samples. At least one TP53 variant was identified in 4 patients’ baseline pre-chemotherapy ctDNA. Both pCR patients had either no detectable ctDNA TP53 mutations, or clearance of ctDNA following chemotherapy. Three non-PCR patients had persistent TP53 mutations in ctDNA during the treatment course. WES and ctDNA analysis on all patients is currently ongoing. Conclusions: We report a very encouraging pCR rate of 46.5% in TNBC patients with carboplatin and docetaxel NAT. This rate is similar to observed rates with anthracycline- and taxane-based NAT and may represent an option for treatment for TNBC patients. Correlative genomic and ctDNA studies are ongoing. Clinical trial information: NCT02124902 & NCT02547987. Citation Format: FOLUSO O ADEMUYIWA, Mothaffar F Rimawi, Tracy Summa, Jingqin Luo, Tao Wang, Rama Suresh, Lindsay Peterson, Michael Naughton, Ashley Frith, Leonel Hernandez-Aya, Katherine Weilbaecher, Cynthia Ma, Aadel A Chaudhuri, Yang-Yang Feng, Zachary L Skidmore, Obi L Griffith, Malachi Griffith, Matthew Ellis. Neoadjuvant treatment of triple negative breast cancer patients with docetaxel and carboplatin to assess anti-tumor activity [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-03.