First‐Line Palliative HER2‐Targeted Therapy in HER2‐Positive Metastatic Breast Cancer Is Less Effective After Previous Adjuvant Trastuzumab‐Based Therapy

Background Survival of patients with human epidermal growth receptor 2 (HER2)‐positive metastatic breast cancer (MBC) has improved dramatically since trastuzumab has become available, although the disease eventually progresses in most patients. This study investigates the outcome (overall survival [...

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Published in:The oncologist (Dayton, Ohio) Ohio), 2017-08, Vol.22 (8), p.901-909
Main Authors: Rier, Hánah N., Levin, Mark‐David, van Rosmalen, Joost, Bos, Monique M. E. M., Drooger, Jan C., de Jong, Paul, Portielje, Johanneke E. A., Elsten, Elisabeth M. P., Ten Tije, Albert‐Jan, Sleijfer, Stefan, Jager, Agnes
Format: Article
Language:English
Subjects:
Adult
Aged
Antibodies, Monoclonal, Humanized - administration & dosage
Biomarkers, Tumor - genetics
Breast Cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Bridged-Ring Compounds - administration & dosage
Chemotherapy, Adjuvant - adverse effects
Clinical Trials as Topic
Disease-Free Survival
Female
Human epidermal growth receptor 2 positive
Humans
Kaplan-Meier Estimate
Metastatic breast cancer
Middle Aged
Neoplasm Metastasis
Neoplasm Recurrence, Local - drug therapy
Neoplasm Recurrence, Local - genetics
Neoplasm Recurrence, Local - pathology
Neoplasm Staging
Overall survival
Palliative Care
Proportional Hazards Models
Receptor, ErbB-2 - genetics
Taxoids - administration & dosage
Trastuzumab
Trastuzumab - administration & dosage
Trastuzumab - adverse effects
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Summary:Background Survival of patients with human epidermal growth receptor 2 (HER2)‐positive metastatic breast cancer (MBC) has improved dramatically since trastuzumab has become available, although the disease eventually progresses in most patients. This study investigates the outcome (overall survival [OS] and time to next treatment [TNT]) in MBC patients pretreated with trastuzumab in the adjuvant setting (TP‐group) compared with trastuzumab‐naïve patients (TN‐group) in order to investigate the possibility of trastuzumab resistance. Patients and Methods Patients treated with first‐line HER2‐targeted‐containing chemotherapy were eligible for the study. A power analysis was performed to estimate the minimum size of the TP‐group. OS and TNT were estimated using Kaplan‐Meier curves and multivariable Cox proportional hazards models. Results Between January 1, 2000, and June 1, 2014, 469 patients were included, of whom 82 were in the TP‐group and 387 were in the TN‐group. Median OS and TNT were significantly worse in the TP‐group compared with the TN‐group (17 vs. 30 months, adjusted hazard ratio [HR] 1.84 [1.15–2.96], p = .01 and 7 vs. 13 months, adjusted HR 1.65 [1.06–2.58], p = .03) after adjustment for age, year of diagnosis, disease‐free interval, hormone receptor status, metastatic site, and cytotoxic regimens. Conclusion First‐line trastuzumab‐containing treatment regimens are less effective in patients with failure of adjuvant trastuzumab compared with trastuzumab‐naïve patients and might be due to trastuzumab resistance. The impact of trastuzumab resistance on the response on dual HER2 blockade with trastuzumab and pertuzumab and how resistance mechanisms can be used in the optimization of HER2‐targeted treatment lines need further investigation. Implications for Practice Evidence on the efficacy of palliative trastuzumab‐based therapy after failure of trastuzumab in the adjuvant setting is limited because of a minority of patients treated with adjuvant trastuzumab in clinical trials. In this study, less clinical benefit of palliative trastuzumab‐based therapy was observed in patients relapsing after adjuvant trastuzumab compared with no adjuvant trastuzumab treatment. Subgroup analyses and multivariable analyses revealed that this was independent of possible confounding factors, including adjuvant taxane‐treatment. This might suggest a clinically meaningful impaired efficacy of trastuzumab after previous, in this case adjuvant, trastuzumab therapy. These
ISSN:1083-7159
1549-490X
DOI:10.1634/theoncologist.2016-0448