1. PHASE III OPEN-LABEL RANDOMIZED
STUDY OF ERIBULIN MESYLATE VERSUS
CAPECITABINE IN PATIENTS WITH LOCALLY
ADVANCED OR METASTATIC BREAST
CANCER PREVIOUSLY TREATED WITH AN
ANTHRACYCLINE AND A TAXANE
Meriam Khalil
PharmD Candidate, Class of
2016
July 27, 2015
Albany College of Pharmacy & Health
Module B:
Ambulatory Care

2. Outline
 Intro/Background:
 Metastatic Breast Cancer
 Eribulin (Halaven)
 Capecitabine (Xeloda)
 Patients & methods
 Study Design
 Study Objectives
 Study Assessment
 QoL Analyses & Statistical Analyses
 Results
 Discussion & conclusion
 Study Analysis

3. Objectives
 Discuss Metastatic Breast Cancer
 Introduce study and summarize key points
 Recommend appropriate treatment strategies

4. Metastatic Breast Cancer
 Overall Survival (OS) has improved.
 Long-term survival remains poor.
 First line
 Anthracycline- or Taxane based regimens
 Neo (adjuvant)
 No single standard of care after failure of
Anthracycline- or Taxane therapy
 Capecitabine (Xeloda): 1st, 2nd, or 3rd line
 Eribulin (Halaven): EMBRACE trial

5. Eribulin Mesylate (Halaven)
Classification: Antimicrotubial agent, non taxane
Mechanism of Action: Inhibits mitotic spindles
Administration: Infusion over 2-5 mins
Indication : Metastatic Breast Cancer who
received 2 prior chemo regimens
Dosage: 1.4 mg/m2 IV on days 1 & 8 every 21
days
Adverse Events: Neutropenia, alopecia, constipation,
Nausea
Interactions : Antiarrythmic agents
Manufacture : Eisai Inc., Woodcliff Lake, NJ

6. Capecitabine
(Xeloda)
Classification: Antimetaboite
Mechanism of Action: Prodrug of 5’ DFUR  5FU
Administration: PO
Indication : First line: Mestastic colon cancer
Dosage: 2000- 2500 mg/m2/day after a meal.
Dose is given for 2 weeks followed by
a 1 week rest period and repeated for
3 cycles.
Adverse Events: Diarrhea, edema, dermatitis, hand-foot
syndrome, neutropenia, nausea
(53%), headache, anemia
Interactions : Antacids. CYP2C9 inhibitors,
leucovorin, phenytoin, anticoagulants
Manufacture : Genentech, Inc., South San
Francisco, CA

7. Patients & Methods

8. Inclusion Criteria
1. Female
2. Age ≥ 18 years
3. Histological or cytologically confirmed breast cancer
4. Up to THREE prior chemotherapy regimens and up to TWO
prior chemotherapy regimens for advanced and/or
metastatic disease
5. Prior therapy with an anthracycline and a taxane
6. Resolution of all chemotherapy- or radiation-related
toxicities to ≤ grade 1 (except for stable sensory
neuropathy ≤ grade 2 and alopecia)
7. Eastern Cooperative Oncology Group performance status
of 0 to 2

9. Exclusion
 Prior capecitabine treatment and radiation
therapy encompassing more than 30% of
marrow.
**Patients with HER2–positive disease could
have received HER2-targeted therapy before
or after study treatment but NOT while on
study treatment.

10. Study Design
 Phase III, randomized, open-label,
parallel, two-arm, multicenter trial
 Stratified patients by geographic
region & HER2 status of their
cancer.

11. Study Objectives
 Compare eribulin & capecitabine in patients with
locally advanced or metastatic breast Cancer
previously treated with an Anthracycline and a
Taxane
 Primary Endpoints:
 Overall Survival (OS)
 Progression- Free Survival (PFS)
 Secondary Endpoints:
 objectives response rate (ORR); duration of
response; 1-, 2-, and 3-year survival; safety; QoL;
and population pharmacokinetic/pharmacodynamic
relationships.

12. Study Assessments
1. Overall survival (OS):
2. Progression-Free survival rate (PFS):
3. Tumor response:
4. Duration of response:
5. Adverse Events:

13. QoL Analyses & Statistical
Analyses
 QoL Analyses
 Two Quality of Life Questionnaires
 At baseline, 6 weeks, and at 3, 6, 18 & 24 months or
until disease progression or initiation of other antitumor
treatments.
 0 (worst) to 100 (best) scale
 Statistical Analyses
 OS & PFS
 Type error 1 was spit; 0.04 for OS and 0.01 for PFS.
 2-sided log rank test
 Interim planned OS analysis
 Tumor response: independent & investigator analysis

14. Interpreting the data
 Positive Study
 Either OS with eribulin was statistically
significantly better (P ≤ .0372) versus
capecitabine
 or PFS with eribulin was statistically
significantly better (P ≤ .01) versus capecitabin
 & the HR for OS (eribulin/capecitabine) was <
1.

15. Results: Patients


16. Results: Efficacy

17. Results: Efficacy

18. Results: Safety

19. QoL Analyses
1. > 95% QoL data= available at baseline
2. Completion rates over time = decreased
3. GHS/QoL scores = low
4. Over time average GHS/QoL scores =
improved
BOTH
ARMS
 Linear mixed model and pattern-mixture model
showed no significant difference between the
groups:
 Linear mixed model  P = .958
 Pattern-mixture model  P = .949

20. Discussion & Conclusion
 Discussion
 Although eribulin is an active single in patients with
MBC, it was not superior to capecitabine with regard
to either OS or PFS.
 Resulted contrasted with those of EMBRACE *
(significant improvement with eribulin compared with
TPC)
 Effects of QoL & AE profiles (of both drug) were
consistent with their known AE.
 Conclusion
Eribulin was NOT shown to be
superior to capecitabine with regard
to OS or PFS.

21. Study Analysis
 Study Design
 Inclusion/Exclusion Criteria
 Interventions
 Objectives/Outcomes
 Statistical Analysis
 Results
 Conclusions

22. Further Analysis
 Strengths:
 Power
Randomized
Intention to treat
 Weaknesses:
 Funded by Eisai
Open – labeled

23. Recommendation
Currently, there is no standard therapy for
patients who have MBC & fail Anthracyclines
or Taxanes
Chemotherapy regimes should be based on
contraindications, drug-drug interaction,
tolerability (side effects) & compliance

24. Questions

25. References
 Phase III Open-Label Randomized Study of Eribulin Mesylate Versus
Capecitabine in Patients With Locally Advanced or Metastatic Breast
Cancer Previously Treated With an Anthracycline and a TaxanePeter A.
Kaufman, Ahmad Awada, Chris Twelves, Louise Yelle, Edith A. Perez,
Galina Velikova, Martin S. Olivo, Yi He, Corina E. Dutcus, and Javier
CortesJCO Feb 20, 2015:594-601; published online on January 20, 2015.