270P - Phase II study of gemcitabine, trastuzumab, and pertuzumab for HER2-positive metastatic breast cancer after prior pertuzumab-based therapy

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Breast Cancer, Metastatic
Presenter Neil Iyengar
Citation Annals of Oncology (2016) 27 (6): 68-99. 10.1093/annonc/mdw365
Authors N.M. Iyengar1, L. Smyth2, D. Lake2, A. Gucalp2, J. Singh2, T.A. Traina2, P. Defusco2, M.N. Dickler2, M. Fornier2, S. Goldfarb2, K. Jhaveri2, A. Latif2, S. Modi2, T. Troso-Sandoval2, G. Ulaner3, M. Jochelson3, J. Baselga2, L. Norton2, C. Hudis2, C. Dang2
  • 1Medicine, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 2Medicine, Memorial Sloan Kettering Cancer Center, New York/US
  • 3Radiology, Memorial Sloan Kettering Cancer Center, New York/US

Abstract

Background

The combination of taxanes with trastuzumab (H) and pertuzumab (P) for first line treatment of HER2-positive metastatic breast cancer (MBC) is associated with improved progression-free survival (PFS) and overall survival (OS). Treatment per physician's choice with anti-HER2 therapy after second line therapy is associated with a median PFS of 3 months. While continued use of H in therapeutic combinations after progression on H-based therapy is common, the efficacy of continuing HP-based treatment after progression on P-based therapy is unknown.

Methods

This is a single arm phase II trial of gemcitabine (G) with HP. Eligible patients had HER2-positive (IHC 3+ or FISH > 2.0) MBC with prior HP-based treatment and ≤ 3 prior chemotherapies. Patients received G (1200 mg/m2) on days 1 and 8 of a q 3 week (w) cycle, and H (8 mg/kg load  →  6 mg/kg) and P (840 mg load  →  420 mg) q3w. The primary endpoint is PFS at 3 months. Secondary endpoints include OS, safety and tolerability. An exploratory endpoint is to compare PFS by RECIST criteria versus 18-F FDG-PET response criteria. Using a Simon optimal 2-stage design, 21 patients were enrolled in stage 1. The successful 3-month PFS rate for stage 1 was set at 57% to allow accrual to stage 2 for a total of 45 patients. The study therapy will be considered successful if at least 27/45 (60%) patients are progression free at 3 months.

Results

As of April 11, 2016, 22 patients are enrolled; 17 are evaluable at 3 months and 5 have not had 3-month evaluation. At 3 months, 12/17 (71%) are progression free (1 CR, 4 PR, 7 SD); 5 patients have progressed. The 3 month-PFS results for evaluable patients will be updated. There are no cardiac or febrile neutropenic events to date. 5 patients required G dose reduction (4 due to grade 3 neutropenia and 1 due to grade 3 vomiting) and the study was amended to lower initial G dose to 1000 mg/m2.

Conclusions

The preliminary 3 month-PFS is 71% in evaluable patients, and updated data will be presented. These findings suggest clinical benefit when P is continued beyond progression.

Clinical trial identification

NCT02252887 September 26, 2014

Legal entity responsible for the study

Memorial Sloan Kettering Cancer Center

Funding

Genentech/Roche

Disclosure

All authors have declared no conflicts of interest.