Ixabepilone plus capecitabine in metastatic breast cancer patients with reduced performance status previously treated with anthracyclines and taxanes: a pooled analysis by performance status of efficacy and safety data from 2 phase III studies

125 Background: BOLERO-2, a phase III study, randomized 724 patients with hormone-receptor–positive metastatic breast cancer, who had recurrence or progression on/after prior nonsteroidal aromatase inhibitor therapy, to everolimus (EVE) + exemestane (EXE) or EXE + placebo. A preplanned 12-mo median time interim analysis demonstrated that EVE + EXE significantly improved progression-free survival (PFS) vs EXE + placebo, but EVE + EXE resulted in a higher rate of grade 3-4 toxicity. Per-protocol patients reported HRQoL data are limited; here we report on additional post hoc analyses of these outcomes. Methods: Using the EORTC QLQ-C30 questionnaire, HRQoL was assessed at baseline and every 6 weeks thereafter until progression. QLQ-C30 consists of 30 items combined into 15 subscales, including a Global Health Status (GHS), where higher scores (range, 0-100) indicate better HRQoL. Analysis included a protocol-specified time to definitive deterioration (TTD) analysis at a 5% decrease in QoL relative to baseline, with no subsequent increase above this threshold. We report additional sensitivity analyses using 10-point minimally important difference (MID) decreases in QLQ-C30 score relative to baseline. Treatment arms were compared using a stratified log-rank test and a Cox proportional hazards model adjusted for trial stratum (visceral metastases and previous hormone sensitivity), age, sex, race, baseline score, ECOG performance status, prognostic risk factors, and treatment history. Results: Baseline QLQ-C30 GHS scores were not statistically significantly different across treatment groups (64.7 vs 65.3; difference –0.7 [95% CI, –4.3-3.0]). Median TTD in HRQoL was 7.0 mo (95% CI, 5.6-8.3) for EVE + EXE vs 5.6 (95% CI, 4.2-7.0) for EXE (p = .0792). Adjusted HR (0.80) approached significance (95% CI, 0.63-1.02). At the 10-point MID, median TTD for EVE + EXE was 9.7 mo (95% CI, 8.3-11.2) vs 8.4 mo (95% CI, 6.3-12.5) for EXE. Adjusted HR was 0.90 (95% CI, 0.69-1.18). Conclusions: These additional analyses from the BOLERO-2 study demonstrate that in addition to significantly improving PFS, EVE + EXE does not compromise HRQoL.

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Efficacy and safety of balugrastim in chemotherapy-induced neutropenia: Integrated analysis of two randomized phase III studies.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e17572 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e17572-e17572

Author(s):

Oleg Gladkov ◽

Constantin D. Volovat ◽

Steven Barash ◽

Anton Buchner ◽

Noa Avisar ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Medical Condition ◽

Phase Iii ◽

Severe Neutropenia ◽

Integrated Analysis ◽

Efficacy And Safety ◽

Breast Cancer Patients ◽

Myelosuppressive Chemotherapy ◽

Phase Iii Studies

e17572 Background: Balugrastim is a recombinant fusion protein composed of human serum albumin and human granulocyte colony-stimulating factor, which allows for once-per-chemotherapy cycle administration. We present a combined analysis of two double-blind, randomized Phase III studies comparing efficacy and safety of balugrastim vs pegfilgrastim in breast cancer patients receiving myelosuppressive chemotherapy (CTx). Methods: All patients were treated with doxorubicin 60 mg/m2 followed by docetaxel 75 mg/m2 administered by i.v. infusion on Day 1 of a 21-day cycle for up to 4 cycles. For each cycle, patients received a single s.c. injection of balugrastim approximately 24 hours after administration of CTx. The primary endpoint for both studies was duration of severe neutropenia (DSN) in Cycle 1. Safety of balugrastim was assessed by evaluating the type, frequency, and severity of adverse events (AEs); changes in laboratory parameters and vital signs, and immunogenicity over time. Analyses were performed in the per-protocol population. Results: A total of 469 patients were randomized to receive balugrastim 40 mg (N=235) or pegfilgrastim 6 mg (N=234). Mean DSN in Cycle 1 was 1.1±1.11 days in patients receiving balugrastim (n=236) and 1.0±1.14 days in patients receiving pegfilgrastim (n=234). Non-inferiority was demonstrated by statistical analysis for balugrastim vs pegfilgrastim for reduction in DSN across studies. Patients treated with balugrastim had a significantly shorter time to ANC recovery in Cycle 1 vs pegfilgrastim (2.0 vs 2.3 days; P=0.015). No other significant differences were seen between treatment groups in either study for any other secondary endpoints in Cycles 1–4. The safety profile was similar for both drugs, with the incidence of AEs consistent with the underlying medical condition and administration of myelosuppressive CTx. Conclusions: In both Phase III studies, non-inferiority was clearly demonstrated for balugrastim 40 mg vs pegfilgrastim 6 mg. Balugrastim is a safe and effective alternative to long-acting pegfilgrastim for reducing DSN in breast cancer patients receiving myelosuppressive chemotherapy. Clinical trial information: 2010-019001-42.

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Ixabepilone plus capecitabine vs capecitabine in patients with metastatic breast cancer receiving ixabepilone in the first line setting: a pooled analysis from two phase III studies.

10.1158/0008-5472.sabcs-6117 ◽

2009 ◽

Cited By ~ 7

Author(s):

L Vahdat ◽

LE Fein ◽

MW Karwal ◽

M Campone ◽

R Peck ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Pooled Analysis ◽

Phase Iii ◽

First Line ◽

Two Phase ◽

Line Setting ◽

Phase Iii Studies

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Ixabepilone plus capecitabine improves overall survival in symptomatic patients with metastatic breast cancer previously treated with anthracycline and taxane in 2 large phase III studies.

10.1158/0008-5472.sabcs-6114 ◽

2009 ◽

Cited By ~ 11

Author(s):

P Conte ◽

H Roche ◽

E Perez ◽

J Sparano ◽

B Xu ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Phase Iii ◽

Large Phase ◽

Previously Treated ◽

Phase Iii Studies

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Comparison between doublet agents versus single agent in metastatic breast cancer patients previously treated with an anthracycline and a taxane: A meta-analysis of four phase III trials

The Breast ◽

10.1016/j.breast.2012.07.014 ◽

2013 ◽

Vol 22 (3) ◽

pp. 314-319 ◽

Cited By ~ 7

Author(s):

Wei-Xiang Qi ◽

Li-na Tang ◽

Ai-na He ◽

Zan Shen ◽

Yang Yao

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Meta Analysis ◽

Single Agent ◽

Metastatic Breast ◽

Phase Iii ◽

Breast Cancer Patients ◽

Phase Iii Trials ◽

Previously Treated

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Randomized Phase III Trial of Ixabepilone Plus Capecitabine Versus Capecitabine in Patients With Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane

Journal of Clinical Oncology ◽

10.1200/jco.2009.24.4244 ◽

2010 ◽

Vol 28 (20) ◽

pp. 3256-3263 ◽

Cited By ~ 148

Author(s):

Joseph A. Sparano ◽

Eduard Vrdoljak ◽

Oliver Rixe ◽

Binghe Xu ◽

Alexey Manikhas ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cox Regression ◽

Karnofsky Performance Status ◽

Performance Status ◽

Metastatic Breast ◽

Phase Iii ◽

Cox Regression Analysis ◽

Significant Difference ◽

Previously Treated

PurposeWe sought to determine whether the combination of ixabepilone plus capecitabine improved overall survival (OS) compared with capecitabine alone in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes.Patients and MethodsA total of 1,221 patients with MBC previously treated with anthracycline and taxanes were randomly assigned to ixabepilone (40 mg/m2intravenously on day 1) plus capecitabine (2,000 mg/m2orally on days 1 through 14) or capecitabine alone (2,500 mg/m2on the same schedule) given every 21 days. The trial was powered to detect a 20% reduction in the hazard ratio (HR) for death.ResultsThere was no significant difference in OS between the combination and capecitabine monotherapy arm, the primary end point (median, 16.4 v 15.6 months; HR = 0.9; 95% CI, 078 to 1.03; P = .1162). The arms were well balanced with the exception of a higher prevalence of impaired performance status (Karnofsky performance status 70% to 80%) in the combination arm (32% v 25%). In a secondary Cox regression analysis adjusted for performance status and other prognostic factors, OS was improved for the combination (HR = 0.85; 95% CI, 0.75 to 0.98; P = .0231). In 79% of patients with measurable disease, the combination significantly improved progression-free survival (PFS; median, 6.2 v 4.2 months; HR = 0.79; P = .0005) and response rate (43% v 29%; P < .0001). Grade 3 to 4 neuropathy occurred in 24% treated with the combination, but was reversible.ConclusionThis study confirmed a previous trial demonstrating improved PFS and response for the ixabepilone-capecitabine combination compared with capecitabine alone, although this did not result in improved survival.

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