"New" metastases are associated with a poorer prognosis than growth of pre-existing metastases in patients with metastatic breast cancer treated with chemotherapy

Christopher Twelves, Javier Cortes, Peter A Kaufman, Louise Yelle, Ahmad Awada, Terri A Binder, Martin Olivo, James Song, Joyce A O'Shaughnessy, Maria Jove, Edith A Perez, Christopher Twelves, Javier Cortes, Peter A Kaufman, Louise Yelle, Ahmad Awada, Terri A Binder, Martin Olivo, James Song, Joyce A O'Shaughnessy, Maria Jove, Edith A Perez

Abstract

Introduction: Progression-free survival (PFS) and overall survival (OS) endpoints often only weakly correlate. This analysis investigates how different progression events impact on OS, using data from two phase 3 studies with eribulin in women with advanced/metastatic breast cancer (MBC).

Methods: In Study 301, 1102 women with ≤2 prior chemotherapies for advanced/MBC were randomized to eribulin mesylate (1.4 mg/m(2) on days 1 and 8 every 21 days) or capecitabine (1.25 g/m(2) twice daily on days 1-14 every 21 days). Study 305/EMBRACE enrolled 762 patients following two to five prior chemotherapies for advanced/MBC, randomized to eribulin (as above) or treatment of physician's choice. We analyzed OS and PFS post hoc for patients whose disease progressed due to development of "new" metastases, growth of pre-existing lesions, and patients with no reported disease progression.

Results: In both clinical studies, development of new metastases was associated with an increased risk of death (p < 0.0001). The time to development of new metastasis or death was significantly longer with eribulin than the comparator in Study 305 (p = 0.0017), but not in Study 301 (p = 0.46). Significantly longer OS was observed in the eribulin compared with the comparator arm for the new metastases subgroup in Study 301 (p = 0.008), but not in Study 305 (p = 0.16), compared with other progression subgroups.

Conclusions: Patients with MBC progressing with new metastases have a worse prognosis than those whose disease progresses due to growth of existing lesions or patients with no reported disease progression. These findings have potentially important implications for the interpretation of clinical study data and clinical practice.

Trial registration: ClinicalTrials.gov registration IDs: Study 301: NCT00337103 ; Study 305: NCT00388726 .

Figures

Fig. 1
Fig. 1
Cumulative incidence function of new metastasis or death in studies (a) 301, and (b) 305/EMBRACE. The data are based on independent review of the intent-to-treat population.
Fig. 2
Fig. 2
New-metasasis–free survival in studies (a) 301 and (b) 305/EMBRACE. The data are based on independent review of the intent-to-treat population. New-metastasis–free survival was defined as the time from randomization to death or disease progression due to a new metastasis (whichever occurred earlier).
Fig. 3
Fig. 3
Time to new metastases in vital organs in studies (a) 301, and (b) 305/EMBRACE. The data are based on independent review of the intent-to-treat population. Vital organs constitute the central nervous system, lungs, or liver.

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