Abstract P1-14-16: Weekly paclitaxel, trastuzumab, carboplatin is a highly effective neoadjuvant regimen in HER2-positive breast cancer: Results from the TRAIN-study
Authors: van Ramshorst MS , van Werkhoven E , Mandjes IAM , Schot M , Wesseling J , Vrancken Peeters M-JTFD , Rodenhuis S , Oosterkamp HM , Bos MEM , Meerum Terwogt JM , Linn SC , Sonke GS 
Published: May 2016

Abstract
Background A trastuzumab/carboplatin/docetaxel regimen is an established alternative for the more commonly used and toxic anthracycline/cyclophosphamide containing regimen in HER2-positive breast cancer. Weekly paclitaxel, however, may be more effective and better tolerable than three-weekly docetaxel.
Aim To assess the efficacy and safety of an anthracycline/cyclophosphamide-free neoadjuvant treatment regimen with weekly paclitaxel, carboplatin and trastuzumab in HER2-positive breast cancer.
Patients and methods The TRAIN-study is a multicenter phase II trial which was developed during the 9th ECCO/AACR/ASCO Workshop on "Methods in Clinical Cancer Research" in Flims, Switzerland. Patients with stage II or III HER2-positive breast cancer were eligible. Treatment consisted of weekly administrations of paclitaxel ([P], 70mg/m2), trastuzumab ([T], 2mg/kg, loading dose 4mg/kg), and carboplatin ([C], AUC = 3mg/ml/minute) for a total of 24 weeks. In cycles 7, 8, 15, 16, 23 and 24 only trastuzumab was administered. The primary endpoint was pathologic complete response (pCR), defined as no residual invasive tumor cells in the breast and axilla. Event-free survival was evaluated as a secondary endpoint. In addition, we report efficacy results in an additional cohort of patients treated with the same regimen after study closure. Toxicity data were only recorded for the study population.
Results Baseline characteristics of 109 study patients and 72 additional patients were similar. The pCR rate in the study population was 43% (95% confidence interval [CI] 33-53%) and in all evaluable patients combined 47% (95% CI 39-54%).
The median follow-up was 41 months (interquartile range [IQR] 20-53). The 3-year event-free survival estimate was 89% (95% CI 84-95%). Patients who achieved a pCR had a better prognosis than patients who did not (hazard ratio [HR] 0.33; 95% CI 0.11-1.00, p&lt;0.05).
In the study population the most common grade 3-4 adverse events were neutropenia (67%) and thrombocytopenia (43%). Febrile neutropenia occurred in less than five percent of patients. During the neoadjuvant treatment period no symptomatic left ventricular systolic dysfunction was observed. Dose reductions were implemented in 56% of study patients and at least one chemotherapy dose was skipped in 67% of patients.
Conclusion Weekly paclitaxel, trastuzumab, and carboplatin is a highly effective neoadjuvant regimen in HER2-positive breast cancer with manageable toxicity. In the currently running randomized TRAIN-2 study this regimen will be directly compared to an anthracycline/cyclophosphamide containing neoadjuvant regimen in the setting of dual HER2-blockade with pertuzumab (clinicaltrials.gov NCT01996267).
Pathologic complete response rate according to population and hormone receptor status All patientsER- and PR-ER+ and/or PR+Study population (n=108)43%53%34%Additional cohort (n=70)53%71%36%Combined population (n=178)47%60%35%
Citation Format: van Ramshorst MS, van Werkhoven E, Mandjes IAM, Schot M, Wesseling J, Vrancken Peeters M-JTFD, Rodenhuis S, Oosterkamp HM, Bos MEM, Meerum Terwogt JM, Linn SC, Sonke GS. Weekly paclitaxel, trastuzumab, carboplatin is a highly effective neoadjuvant regimen in HER2-positive breast cancer: Results from the TRAIN-study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-16.