Abstract P4-12-07: Neoadjuvant trastuzumab emtansine and docetaxel, with or without pertuzumab, in patients with HER2-positive early-stage breast cancer: Results from a phase 1b/2a study
Authors: Martin M , Dewar J , Albanell J , Limentani S , Chang J , Strasak A , Patre M , Garcia-Sáenz JA 
Published: August 2014

Abstract
Introduction
Trastuzumab emtansine (T-DM1) is an antibody–drug conjugate comprising trastuzumab, a stable linker, and DM1 (a microtubule inhibitor). T-DM1 prolonged PFS and OS compared with standard therapy in a phase 3 study in patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) previously treated with trastuzumab and a taxane and was well tolerated (Verma, NEJM 2012). When combined with docetaxel (D) or pertuzumab (P), T-DM1 antitumor activity was enhanced in preclinical models of HER2-positive breast cancer (Lewis-Phillips, AACR 2008; Fields, AACR 2010). The feasibility of combining T-DM1 with D±P in patients with HER2-positive MBC and early-stage breast cancer (EBC) was demonstrated in phase 1b of study BP22572, in which the maximum tolerated doses (MTDs) were defined (Martin, SABCS 2012). Here we report on patients with EBC who were treated at the MTDs in phases 1b and 2a of the study.
Methods
BP22572 is a phase 1b/2a open-label, multicenter study evaluating neoadjuvant T-DM1 with D±P in patients with centrally confirmed HER2-positive EBC (clinical stage IIa–IIIc) who have not received prior anticancer therapy. Patients with EBC were treated for up to 6 cycles at the doses specified in the Table.
Results
Recruitment into the neoadjuvant cohorts was completed in November 2012; the data cutoff date for analyses presented here was May 2, 2013. A total of 70 patients were treated with the combinations (median age, 51.5 years [range, 34–76]). Grade 3/4 adverse events (AEs) were reported for 51 (72.9%) patients; those occurring in &gt;1 patient are shown in the Table. One patient in the T-DM1 + D 100 mg/m2 cohort experienced grade 5 pneumonitis shortly after an episode of neutropenic fever. As of the data cutoff date, all patients had received neoadjuvant treatment, but not all had undergone surgery. Pathologic complete response (pCR; ypT0/is ypN0, absence of invasive disease or in situ disease only in the breast and negative axillary nodes) was achieved in 40 of 70 treated patients (preliminary pCR rate, 57.1%).
Grade 3/4 AEs occurring in &gt;1 patientAE, n (%)All patients (N = 70)T-DM1 3.6 mg/kg + D 75 mg/m2 q3w (n = 15)T-DM1 3.6 mg/kg + D 100 mg/m2 q3w (with G-CSF) (n = 22)T-DM1 3.6 mg/kg + D 60 mg/m2 + P 840 mg LD, then 420 mg q3w (n = 11)T-DM1 3.6 mg/kg + D 75 mg/m2 + P 840 mg LD, then 420 mg q3w (with G-CSF) (n = 22)Neutropenia21 (30)7 (47)2 (9)7 (64)5 (23)Thrombocytopenia14 (20)2 (13)6 (27)—6 (27)ALT increased11 (16)3 (20)3 (14)3 (27)2 (9)Asthenia6 (9)2 (13)2 (9)1 (9)1 (5)AST increased5 (7)2 (13)1 (5)—2 (9)Lymphopenia3 (4)—2 (9)—1 (5)Mucosal inflammation3 (4)—2 (9)—1 (5)Anemia2 (3)—1 (5)—1 (5)Febrile neutropenia2 (3)—1 (5)—1 (5)Leukopenia2 (3)1 (7)—1 (9)—Diarrhea2 (3)——1 (9)1 (5)
Conclusions
Grade 3/4 AE profiles were consistent with the known safety profiles of the 3 agents in patients with MBC. There was 1 grade 5 event (pneumonitis) in the T-DM1 + D 100 mg/m2 cohort. Preliminary pCR data are encouraging. Final safety and efficacy data from all patients in phase 2a of the study will be available for the presentation.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-07.