Case study*

P.V., a patient with mBC with visceral metastases

Patient history and treatment
  • P.V. is a 49-year-old premenopausal woman and stay-at-home mother to 2 daughters

  • She was in generally good health prior to her breast cancer diagnosis

  • In 2010, she was diagnosed with breast cancer

    • Multifocal invasive ductal carcinoma (measuring 0.2-0.6 cm)

    • Extensive ductal carcinoma in situ and lobular carcinoma in situ

  • P.V. underwent left mastectomy with immediate breast reconstruction by TRAM flap surgery

INITIAL SURGERY/LABORATORY FINDINGS
Tumor Type Multifocal invasive ductal carcinoma Lymph node status 2/20
Clinical tumor size 0.2-0.6 cm ER status Positive
Histologic grade 2 PR status Positive
Stage IIB HER2/neu status Negative
Tumor Type Multifocal invasive ductal carcinoma
Clinical tumor size 0.2-0.6 cm
Histologic grade 2
Stage IIB
Lymph node status 2/20
ER status Positive
PR status Positive
HER2/neu status Negative

TRAM=transverse rectus abdominis myocutaneous; ER=estrogen receptor; PR=progesterone receptor; HER2/neu=human epidermal growth factor receptor 2.

Adjuvant treatment
  • P.V. was treated with 4 cycles of dose-dense AC followed by 12 weeks of weekly paclitaxel before switching to tamoxifen

    • P.V. tolerated chemotherapy poorly; she became hypotensive and fell, suffering a maxillary fracture

    • Tamoxifen was reasonably well tolerated; P.V. gained weight and resumed menses

Visceral metastases and initial mBC treatment
  • P.V. received regular follow-ups; 25 months after starting tamoxifen, she presented with symptoms of kidney stones. A non-contrast CT scan of the abdomen and pelvis had incidental finding of suspicious liver lesions

    • A PET scan revealed 3 liver lesions (measuring 1-2 cm), and 2 bone lesions in the sternum and T10 vertebra

  • A liver biopsy confirmed metastatic disease consistent with primary ER+/PR+, HER2/neu-negative breast cancer

  • P.V. was asymptomatic and did not wish to consider chemotherapy, and her physician did not feel it was necessary

    • P.V. started on endocrine therapy, OFS, and denosumab, with good initial response

    • After 7 months of endocrine therapy, P.V. presented with progressive disease in the liver and bone

AC=doxorubicin/cyclophosphamide; CT=computed tomography; PET=positron emission tomography; OFS=ovarian function suppression.

*This case study presents a hypothetical patient. HALAVEN® (eribulin mesylate) Injection (0.5 mg per mL) is not appropriate for all patients. This information should not substitute for the independent medical judgment of the treating physician.

Anthracyclines were the standard of care in adjuvant treatment at the time.

mBC treatment history

PREVIOUS CHEMOTHERAPIES FOR MBC

Clinical findings

  • ECOG PS: 1

LABORATORY FINDINGS
PARAMETER PATIENT P.V.'S RESULTS
Liver ALP 292 U/L
AST 80 U/L
ALT 59 U/L
Serum albumin 3.2 g/dL
WBC 3.4 x 103/μL
Hemoglobin 9.8 g/dL
Platelets 105 x 103/μL
Bilirubin 0.9 mg/dL
INR 1.1

ECOG PS=Eastern Cooperative Oncology Group performance status; ALP=alkaline phosphatase; AST=aspartate aminotransferase; ALT=alanine aminotransferase; WBC=white blood cell; INR=international normalized ratio.


WHAT TREATMENT WOULD YOU RECOMMEND FOR PATIENT P.V., GIVEN HER VISCERAL METASTASES AND HER TREATMENT HISTORY?


Based on the Phase III EMBRACE trial, P.V. was identified as appropriate for treatment with HALAVEN®1

After receiving an anthracycline and a taxane in the adjuvant setting and following 2 prior chemotherapies for mBC, P.V. may begin third-line treatment with HALAVEN

SELECTED PATIENT FACTORS

EMBRACE=Eisai Metastatic Breast Cancer Study Assessing Physician's Choice versus E7389 (Eribulin).

*Subject to patient eligibility.

Indications

Metastatic Breast Cancer

HALAVEN (eribulin mesylate) Injection is indicated for the treatment of patients with metastatic breast cancer (mBC) who have previously received at least 2 chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.

Liposarcoma

HALAVEN is indicated for the treatment of patients with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen.

Important Safety Information

Warnings and Precautions

Neutropenia: Severe neutropenia (ANC <500/mm3) lasting >1 week occurred in 12% of patients with mBC and liposarcoma or leiomyosarcoma. Febrile neutropenia occurred in 5% of patients with mBC and 2 patients (0.4%) died from complications. Febrile neutropenia occurred in 0.9% of patients with liposarcoma or leiomyosarcoma, and fatal neutropenic sepsis occurred in 0.9% of patients. Patients with mBC with elevated liver enzymes >3 × ULN and bilirubin >1.5 × ULN experienced a higher incidence of Grade 4 neutropenia and febrile neutropenia than patients with normal levels. Monitor complete blood cell counts prior to each dose, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. Delay administration and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting >7 days.

Peripheral Neuropathy: Grade 3 peripheral neuropathy occurred in 8% of patients with mBC (Grade 4=0.4%) and 22% developed a new or worsening neuropathy that had not recovered within a median follow-up duration of 269 days (range 25-662 days). Neuropathy lasting >1 year occurred in 5% of patients with mBC. Grade 3 peripheral neuropathy occurred in 3.1% of patients with liposarcoma and leiomyosarcoma receiving HALAVEN and neuropathy lasting more than 60 days occurred in 58% (38/65) of patients who had neuropathy at the last treatment visit. Patients should be monitored for signs of peripheral motor and sensory neuropathy. Withhold HALAVEN in patients who experience Grade 3 or 4 peripheral neuropathy until resolution to Grade 2 or less.

Embryo-Fetal Toxicity: HALAVEN can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with HALAVEN and for at least 2 weeks following the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with HALAVEN and for 3.5 months following the final dose.

QT Prolongation: Monitor for prolonged QT intervals in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities. Correct hypokalemia or hypomagnesemia prior to initiating HALAVEN and monitor these electrolytes periodically during therapy. Avoid in patients with congenital long QT syndrome.

Adverse Reactions

In patients with mBC receiving HALAVEN, the most common adverse reactions (≥25%) were neutropenia (82%), anemia (58%), asthenia/fatigue (54%), alopecia (45%), peripheral neuropathy (35%), nausea (35%), and constipation (25%). Febrile neutropenia (4%) and neutropenia (2%) were the most common serious adverse reactions. The most common adverse reaction resulting in discontinuation was peripheral neuropathy (5%).

In patients with liposarcoma and leiomyosarcoma receiving HALAVEN, the most common adverse reactions (≥25%) reported in patients receiving HALAVEN were fatigue (62%), nausea (41%), alopecia (35%), constipation (32%), peripheral neuropathy (29%), abdominal pain (29%), and pyrexia (28%). The most common (≥5%) Grade 3-4 laboratory abnormalities reported in patients receiving HALAVEN were neutropenia (32%), hypokalemia (5.4%), and hypocalcemia (5%). Neutropenia (4.9%) and pyrexia (4.5%) were the most common serious adverse reactions. The most common adverse reactions resulting in discontinuation were fatigue and thrombocytopenia (0.9% each).

Use in Specific Populations

Lactation: Because of the potential for serious adverse reactions in breastfed infants from eribulin mesylate, advise women not to breastfeed during treatment with HALAVEN and for 2 weeks after the final dose.

Hepatic and Renal Impairment: A reduction in starting dose is recommended for patients with mild or moderate hepatic impairment and/or moderate or severe renal impairment.

 

Reference: 1. Data on file, Eisai Inc.