Indication

IXEMPRA is indicated as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine.

Study 081: IXEMPRA
monotherapy

Study objective

To evaluate the efficacy and safety of IXEMPRA® (ixabepilone) in patients with metastatic or locally advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine.1

Study design

Study design and baseline characteristics

Study 081 design1,2

IXEMPRA® (ixabepilone) Study 081 was a phase 2, single-arm, multicenter trial of patients with metastatic or locally advanced breast cancer (N=126)

HER2, human epidermal growth factor receptor 2; ORR, objective tumor response rate; RECIST, Response Evaluation Criteria in Solid Tumors.

* For anthracyclines, patients who received a minimum cumulative dose of 240 mg/m2 of doxorubicin or 360 mg/m2 of epirubicin were also eligible.2

As determined by independent radiologic review.2

Study 081 baseline patient demographics and clinical characteristics1

IXEMPRA® (ixabepilone) monotherapy Study 081 baseline patient demographics and clinical characteristics

ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; IRF, independent radiology facility; PR, progesterone receptor.

* Two of the 128 patients enrolled were not treated: elevated total bilirubin precluded treatment in one patient, and the other refused treatment.

Defined as positive by fluorescence in situ hybridization and/or 3+ by immunohistochemistry.

HER2 testing was not performed routinely in sites in Latin America.

Efficacy

As monotherapy, IXEMPRA® (ixabepilone) demonstrated an objective tumor response rate of 12.4% and 18.3% (IRR vs IA, respectively)2

As monotherapy, IXEMPRA® (ixabepilone) demonstrated an objective tumor response rate of 12.4% and 18.3% (IRR vs IA, respectively)

CI, confidence interval; IA, investigator assessment; IRR, independent radiologic review; ORR, objective tumor response rate.

* IXEMPRA was administered at a dose of 40 mg/m2 IV over 3 hours every 3 weeks. Patients received a median of 4 cycles (range, 1-18).

All responses were partial.

As assessed by IRR.

  • Approximately 70% of patients received IXEMPRA after initial taxane failure3
  • Objective tumor response rates2:
    • IRR* (n=113): 12.4% (95% CI, 6.9%-19.9%)
    • IA (N=126): 18.3% (95% CI, 11.9%-26.1%)
  • Median time to response by IRR (n=14) was 6.1 weeks (min-max, 5-54.4)2
  • Median duration of response by IRR (n=14) was 6.0 months (95% CI, 5.0-7.6)2
* All responses were partial.

Patient profile

Trina

IXEMPRA® (ixabepilone) patient profile Trina* | Age: 45 years—perimenopausal

DIAGNOSIS

Initial stage

  • Palpable mass in the right breast
  • Mammography revealed 3.5-cm mass
  • Ultrasound-guided biopsy confirmed presence of invasive ductal carcinoma
  • Chest X-ray, bone scan, and CT scan were negative for metastatic disease

Receptor status

  • ER−, PR−, HER2/neu−

TREATMENT HISTORY

  • Underwent a mastectomy with axillary node dissection performed approximately 1 month after initial presentation
  • 6 of 12 axillary nodes contained macrometastases, and 1 contained 2-mm micrometastasis (pT2N2)

Adjuvant

  • Adjuvant therapy (AC–>T) initiated
  • Patient subsequently received radiation therapy

PRESENTATION

General

  • 9 months after completion of adjuvant therapy, patient complained of abdominal pain and shortness of breath on mild exertion; unable to work a full day due to severe fatigue

Sites of metastases

  • Multiple liver and lung lesions

Pertinent labs

  • CT-guided biopsy of one of the liver nodules was consistent with invasive ductal carcinoma
  • Receptor status confirmed as ER−, PR−, and HER2/neu−
  • LFT (AST/ALT) values were normal
  • Neutrophil and platelet counts were within normal limits

FIRST-LINE METASTATIC CHEMOTHERAPY

  • 16 months after surgery, patient was started on docetaxel plus capecitabine
  • Further anthracycline therapy was contraindicated
  • Patient progressed within 4 months
Trina reached the IXEMPRA® (ixabepilone) Zone for monotherapy

AC–>T, doxorubicin and cyclophosphamide followed by taxane (docetaxel or paclitaxel); ALT, alanine aminotransferase; AST, aspartate aminotransferase; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; LFT, liver function test; PR, progesterone receptor; Tx, treatment.

* Hypothetical patient profile. Photo not of actual patient.

Further anthracycline therapy was contraindicated.

Reflects approved indications for IXEMPRA.

Safety profile

Safety profile of IXEMPRA® (ixabepilone) monotherapy2

Study 081 peripheral neuropathy

Safety profile of IXEMPRA® (ixabepilone) as monotherapy * Sensory and motor neuropathy combined.
  • Prior therapy with neurotoxic chemotherapy agents did not predict the development of neuropathy
  • Peripheral neuropathy was common and primarily sensory
  • Neuropathy is cumulative and generally reversible and should be managed with dose adjustments and delays
    • The median time to improvement of grades 3/4 neuropathy to baseline or grade 1 was 4.6 weeks
    • Following dose reduction, 87% of patients had improvement or no worsening of their neuropathy
    • Discontinuation due to neuropathy was 6%

Study 081 hematologic abnormalities

Continued safety profile of IXEMPRA® (ixabepilone) as monotherapy

Hgb, hemoglobin; WBC, white blood cell count.

* Granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) was used in 17% of patients who received IXEMPRA in Study 081.

In clinical trials, febrile neutropenia was classified as a nonhematologic adverse reaction.

  • Infection with neutropenia was reported in 5% of patients treated with IXEMPRA as monotherapy

Study 081 nonhematologic drug-related adverse reactions occurring in ≥5% of patients

IXEMPRA® (ixabepilone) as monotherapy Study 081 nonhematologic drug-related adverse reactions occurring in ≥5% of patients

* System organ class presented as outlined in Guidelines for Preparing Core Clinical-Safety Information on Drugs by the Council for International Organizations of Medical Sciences (CIOMS).

A composite of multiple MedDRA Preferred Terms.

No grade 4 reports.

§ Peripheral sensory neuropathy (graded with the National Cancer Institute Common Terminology Criteria [NCI CTC] scale) was defined as the occurrence of any of the following: areflexia, burning sensation, dysesthesia, hyperesthesia, hypoesthesia, hyporeflexia, neuralgia, neuritis, neuropathy, neuropathy peripheral, neurotoxicity, painful response to normal stimuli, pallanesthesia, paresthesia, peripheral sensory neuropathy, polyneuropathy, polyneuropathy toxic, and sensorimotor disorder.

|| Peripheral motor neuropathy (graded with the NCI CTC scale) was defined as the occurrence of any of the following: multifocal motor neuropathy, neuromuscular toxicity, peripheral motor neuropathy, and peripheral sensorimotor neuropathy.

Indications and Important Safety Informationexpand

Indications

IXEMPRA® (ixabepilone) is indicated in combination with capecitabine for the treatment of patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated.

  • Anthracycline resistance is defined as progression while on therapy or within 6 months in the adjuvant setting or 3 months in the metastatic setting
  • Taxane resistance is defined as progression while on therapy or within 12 months in the adjuvant setting or 4 months in the metastatic setting

IXEMPRA is indicated as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine.

Important Safety Information
WARNING: Toxicity in hepatic impairment

Contraindications

Peripheral neuropathy

Myelosuppression

Hypersensitivity reaction

Pregnancy

Cardiac adverse reactions

Potential for cognitive impairment from excipients

Adverse reactions

Monotherapy

Combination with capecitabine

Cremophor is a registered trademark of BASF AG.

AST = aspartate aminotransferase; ALT = alanine aminotransferase; ULN = upper limit of normal; CTC = common terminology criteria.

Indications

IXEMPRA® (ixabepilone) is indicated in combination with capecitabine for the treatment of patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated.

  • Anthracycline resistance is defined as progression while on therapy or within 6 months in the adjuvant setting or 3 months in the metastatic setting
  • Taxane resistance is defined as progression while on therapy or within 12 months in the adjuvant setting or 4 months in the metastatic setting

IXEMPRA is indicated as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine.

Please see US Full Prescribing Information, including boxed WARNING regarding hepatic impairment.

References: 1. Perez EA, Lerzo G, Pivot X, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2007;25(23):3407-3414. 2. IXEMPRA (ixabepilone) Prescribing Information; January 2016. 3. Data on file: IXEM005. R-Pharm US: Princeton, NJ; 2006.

To view this site properly, you will need to update your browser to the most current version.