Abstract OT3-1-08: A phase II, randomized study of T-DM1 versus T-DM1 plus short induction with docetaxel in first line treatment for locally advanced or metastatic HER2+ breast cancer (SOLTI-1203)
Authors: Llombart Antonio , Cortés Javier , Ciruelos Eva , González Xavier , de la Peña Lorena , Villagrasa Patricia , Bernedo Elena , Moreno Katya , Meya Susanne , Baselga Jose 
Published: May 2015

Abstract
Background: This study is founded upon the hypothesis that the addition of a short induction phase with docetaxel to the treatment with T-DM1 can improve efficacy with respect to T-DM1 administered as a single agent, in patients with advanced HER2 positive breast cancer who have not received previous treatment for the advanced disease. The rational for this approach is based on the results of the phase II randomized study of T-DM1 versus docetaxel trastuzumab, in which the administration of T-DM1 to the patients resulted in a statistically significant and clinically relevant improved progression free survival (PFS). One important observation with respect to this comparative study is that, in the T-DM1 arm, a higher number of patients progressed during the first six months than in the docetaxel trastuzumab arm. The existence of T-DM1 resistant patients, who progress during the first 6 months, highlights the need to explore new combinations with cytotoxic agents to induce an early response.
Study design: This is a phase II, prospective, randomized, open label, research study with two groups designed to assess the efficacy of T-DM1 together with short induction with docetaxel (SI docetaxel) versus T-DM1monotherapy treatment, in patients recently diagnosed with locally advanced or metastatic, progressive or recurrent, HER2+ breast cancer, who have not received previous chemotherapy for the advanced disease. The randomization will be carried out at a 1:1 ratio to one of the following two groups: 1.Monotherapy treatment regimen with T-DM1 at a dose of 3.6 mg/kg every 3 weeks until treatment finalization, 2.T-DM1 at a dose of 3.6 mg/kg on Day 1 and every 3 weeks until treatment finalization, together with docetaxel 60 mg/mg2 on Day 1 and every 3 weeks for a total of 4 treatment cycles.
Eligibility criteria: Female adults recently diagnosed with progressive or recurrent, locally advanced or metastatic HER2+ breast cancer, who have not received previous chemotherapy for the advanced disease.
Endpoints: The primary endpoint is to compare the early efficacy of the combination of T-DM1 together with SI docetaxel versus monotherapy treatment with T-DM1 measured as the PFS rate at 4 months. Secondary endpoints include comparison of the ORR, CBR, DR and OS of the combination versus monotherapy treatment Exploratory endpoints consist to assess if the PAM50 intrinsic subtypes (HER2-enriched in comparison with the rest) predict benefit of T-DM1 plus SI docetaxel or T-DM1 as monotherapy treatment, in terms of ORR and PFS.
Statistical methods: The considerations for the sample size are based on obtaining a statistical power of 80 % to be able to detect a difference in the rate of PFS at 4 months of 8% (83% in group A and 91% in group B), with a bilateral significance level of 5% and supposing a patient withdrawal rate of 10%. According to these calculations, the sample size is estimated at 236 patients. The analysis of the primary endpoint will be based on the Kaplan Meier estimate analysis.
Target accrual: Approximately 40 European sites from Spain, Portugal and Austria will be participating. The FPI is planned in October 2014.
Citation Format: Antonio Llombart, Javier Cortés, Eva Ciruelos, Xavier González, Lorena de la Peña, Patricia Villagrasa, Elena Bernedo, Katya Moreno, Susanne Meya, Jose Baselga. A phase II, randomized study of T-DM1 versus T-DM1 plus short induction with docetaxel in first line treatment for locally advanced or metastatic HER2+ breast cancer (SOLTI-1203) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT3-1-08.