A phase II study of weekly carboplatin and nab-paclitaxel with trastuzumab or bevacizumab as neoadjuvant therapy for patients with early-stage nonmetastatic breast cancer.

person Elham Vosoughi University of California, Irvine, Orange, CA info_outline Elham Vosoughi, Nellie Nafissi, Aditya Mahadevan, Seungshin Lee, Kritisha Parajuli, Nejina Rijal, Erin Lin, Paul Coluzzi, Ritesh Parajuli, Rita S. Mehta

Authors person Elham Vosoughi University of California, Irvine, Orange, CA info_outline Elham Vosoughi, Nellie Nafissi, Aditya Mahadevan, Seungshin Lee, Kritisha Parajuli, Nejina Rijal, Erin Lin, Paul Coluzzi, Ritesh Parajuli, Rita S. Mehta Organizations University of California, Irvine, Orange, CA, UC Irvine Health, Chao Family Comprehensive Cancer Center, Orange, CA, Nepal Medical College, Kathmandu, Nepal, Kathmandu Medical College, Kathmandu, Nepal, University of California Irvine Medical Center, Orange, CA Abstract Disclosures Research Funding Institutional Funding Sponsor: University of California, Irvine Background: Neo-Adjuvant chemotherapy (NAC) allows patients to undergo breast conserving surgery, treats micro metastatic disease and improves patient outcomes. Achieving a complete pathologic response to NACT has prognostic significance in HER2+ and triple negative breast cancer. Anthracyclines are commonly integrated to Neo-adjuvant regimens. Their use is limited by cardiac and hematologic toxicity. We proposed that weekly Carboplatin and Nab-Paclitaxel is a well-tolerated regimen and aim to demonstrate that this approach can be a selective anthracycline sparing regimen with comparable improvement in recurrence free survival (RFS) and pathologic complete response (pCR). Methods: We conducted a single institution, open label, prospective Phase II clinical trial for patients with non-metastatic breast cancer who were eligible to receive NACT. All Patients with stage I-III breast cancers were treated with weekly Nab-paclitaxel (90 mg/m2) and carboplatin (AUC 2) for 12 weeks. Patients with HER2+ breast cancer received trastuzumab (4 mg/kg induction, followed by 2 mg/kg/week) weekly for 12 weeks. Triple negative and HR + patients received bevacizumab (10 mg/kg) every other week for 5 doses. Results: We enrolled 125 patients from February 2008 to December 2015. 85 pts were HER2- and 42 pts were HER2+. The pCR rate was 17.6% (15 pts) in the HER2- cohort and 50% (21 pts) in the HER2+ cohort. In the subgroup analysis based on hormone receptor (HR) status, pts with HR- tumor had more favorable response with higher rate of pCR compared with pts with HR+ tumor. In the HER2- cohort, the total pCR rate was 34% in HR- tumors vs 8% in HR+ tumors, P = 0.0018. After a median follow up of 53 months, overall survival was 88.9% for pts who achieved pCR and 77.7% for those who did not. HR = 0.3664, CI = 0.06147 to 2.1843, P = 0.34.In the HER2+ cohort the pCR rate was 33% in pts with HR+ tumors vs 72% in pts with HR- tumor, P = 0.0137. After a median follow up of 53 months, overall survival was 100% for pts who achieved pCR vs 20% in those who did not. The relapse-free survival was 90% vs 25% respectively (HR = 0.0669, CI = 0.00454 to 0.9251 P = 0.0016). In the entire study population, 6 pts (4.7%) had treatment discontinuation and 12 pts (9.4%) had dose reduction due to side effects. The rate of treatment disruption was higher in the HER2- cohort. Nausea, vomiting, and neutropenia were the most common side effects in both cohorts (7.9%) followed by thrombocytopenia and anemia (4.7%). Hematologic toxicity was the most common toxicity grade 3 and 4. Conclusions: Combination of nab-paclitaxel and carboplatin plus targeted therapy as an anthracycline sparing neoadjuvant chemotherapy showed a good pCR rate in HER2+ subgroup and moderate activity in TNBC subset. High rate of pCR was associated with high survival outcomes in HER2+ cohort. The regimen was well tolerated among both cohorts. Clinical trial information: NCT00618657.

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