Abstract P3-14-14: Neoadjuvant phase II trial with carboplatin and eribulin in triple negative breast cancer patients
Authors: Giordano SB , Jeruss JS , Bethke KP , Hansen NM , Khan S , Von Roenn J , Rosen S , Gradishar WL , Siziopikou KP , Meservey C , Kaklamani V 
Published: August 2014

Abstract
Background:
Several neoadjuvant trials have been conducted directed at treating triple negative breast cancer (TNBC) patients with platinum agents with pathologic complete response (pCR) rates ranging from 16%-32%. Eribulin mesylate, a nontaxane microtubule dynamics inhibitor with a novel mechanism of action, has clinical activity as monotherapy in breast cancer and other solid tumors. A recent phase I trial found that the combination of eribulin mesylate with carboplatin was well tolerated and showed activity in advanced solid tumors. The recommended dose for future trials was eribulin mesylate 1.1 mg/m2 and carboplatin AUC6. We proposed a neoadjuvant phase II trial with the combination of carboplatin and eribulin in patients with TNBC.
Methods:
30 patients were enrolled between November 2011 and February 2013. Patients received eribulin at 1.4 mg/m2 (intravenously over 2-5 minutes) on days 1 and 8 followed by carboplatin AUC = 6 (intravenously over 30 minutes) on day 1 every 21 days for a total of 4 cycles. Definitive surgery was performed 3-8 weeks after completion of therapy.
Our primary endpoint was to determine the pCR in TNBC patients treated with the combination of carboplatin and eribulin. Secondary objectives included determination of the clinical response rate, residual cancer burden (RCB), toxicity evaluation, in addition to correlative markers including TLE3, Smad3, cyclins/CDKs, and PIN1 and the Homologous Recombination Deficiency Assay (HRD).
Results:
There was an initial safety run-in to evaluate the appropriate dose of eribulin in the study population. After the 10th patient, the study was temporarily suspended; toxicity was assessed for the first 10 patients (cycle 1 only) to assess whether eribulin at 1.4mg/m2 or a dose reduction to 1.1 mg/m2 would be required for the remaining patients. Of the first 10 patients, only 2 of 10 experienced grade 3 or 4 neutropenia, and 0 of 10 patients experienced grade 3 or 4 peripheral neuropathy. Therefore, the study was continued for the remaining 20 patients with eribulin dosed at 1.4 mg/m2 and carboplatin AUC = 6.
Thirty of the planned 30 patients have been enrolled to date. Of the 30 patients, 24 have completed therapy and 6 are currently on study. Of the 24 patients who have completed therapy, 11 have achieved a pCR (45.83%). As for clinical response rates, 5 have had stable disease (20.8%), 5 have had a complete response (20.8%), and 13 have had a partial response (54.2%). Final results will be presented at the time of the meeting including pCR, RCB, toxicity and correlative studies.
The combination of eribulin and carboplatin was well tolerated with a predictable side effect profile. Of the 24 patients who have completed therapy, 8 (33%) required a dose reduction in eribulin for grade 3 or 4 neutropenia. One patient had neutropenic fever. There were no dose reductions for thrombocytopenia thus far. Correlative studies are in progress.
Conclusion:
The combination of carboplatin and eribulin in the neoadjuvant setting appears to be safe and efficacious in patients with TNBC. Statistical analysis on outcomes for the entire study population and correlative study results on pre- and post-treatment tissues are forthcoming. Future randomized clinical trials should evaluate further this regimen.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-14.