PATHOLOGICAL COMPLETE RESPONSE TO TRASTUZUMAB SUBCUTANEOUS FIXED-DOSE FORMULATION IN THE HANNAH STUDY: SUBGROUP ANALYSIS OF PATIENT DEMOGRAPHICS AND TUMOR CHARACTERISTICS AND INFLUENCE OF BODY WEIGHT (BW) AND SERUM TROUGH CONCENTRATION (CTROUGH) OF T

Background

Intravenous (IV) trastuzumab (H) is the standard of care for HER2-positive breast cancer. The Phase III, neoadjuvant-adjuvant HannaH study (Jackisch et al. EBCC 2012) demonstrated the non-inferiority of H subcutaneous (SC) vs. H-IV with respect to serum Ctrough of H and pathological complete response (pCR), with comparable safety profiles for the two formulations. The aim of the presented analyses was to determine whether pCR rates (H-SC vs. H-IV) were consistent across subgroups, and to investigate the relationship of pCR with BW and serum Ctrough of H.

Methods

Subgroup analyses of pCR were performed in the per-protocol population (PPP) based on patient demographics (race, age [< 65 and ≥ 65 years]) and disease characteristics (breast cancer type/subtype/histological grade, hormone receptor status). Further analyses, including multiple logistic regression (MLR), investigated the relationship of pCR rate with BW and serum Ctrough of H. Covariates in the MLR model included treatment arm, serum Ctrough, BW, and all interactions between covariates, in order to account for the different dosing schemes (BW-based vs. fixed dosing).

Results

pCR subgroup analyses showed that the numerically higher pCR rate point estimate in H-SC vs. H-IV was reflected in the majority of subgroups, with all confidence intervals for the rate difference (SC-IV) containing ‘0‘. The findings of the PPP analysis were supported by results obtained in the ITT population. Further analyses, including MLR, showed that neither BW nor serum Ctrough of H correlated with pCR rates in either treatment arm.

Conclusions

BW and serum Ctrough of H did not impact on efficacy (pCR). The 600 mg fixed dose of H-SC is efficacious irrespective of BW. This finding supports H-SC as a treatment alternative to the registered IV formulation.

Disclosure

B. Melichar: Prof. Melichar has participated in advisory board meetings and received honoraria from F. Hoffmann-La Roche Ltd.

J. Li: Jing Li is an employee of F. Hoffmann La-Roche Ltd, and owns stock in Roche Holdings.

T. van der Horst: Tina van der Horst is an employee of F. Hoffmann-La Roche Ltd.

S. Muehlbauer: Susanne Muehlbauer is an employee of F. Hoffmann-La Roche Ltd and owns stock in Roche Holdings.

C. Jackisch: Christian Jackisch has participated in advisory board meetings for F. Hoffmann-La Roche Ltd.

All other authors have declared no conflicts of interest.

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a v 
Ann Oncol (2012) 23 (suppl 9)