for:

HER2+ Advanced or Metastatic Breast Cancer (aBC or mBC)

Important Safety Information, including Boxed WARNING
WARNING: Hepatotoxicity has been observed in clinical trials and postmarketing experience. The hepatotoxicity may be severe and deaths have been reported. Causality of the deaths is uncertain.
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Indication

TYKERB® (lapatinib) is indicated in combination with capecitabine for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab.1

Limitation of use: Patients should have disease progression on trastuzumab prior to initiation of treatment with TYKERB in combination with capecitabine.1

EFFICACY

Trial Design

  • TYKERB (lapatinib) was studied in a phase 3 clinical trial of 399 women with advanced or metastatic HER2+ breast cancer who had progressed after prior treatment that included an anthracycline, a taxane, and trastuzumab1
  • Approximately 95% of patients had prior treatment with an anthracycline, a taxane, and trastuzumab1
  • Patients were randomized into 2 treatment arms1:
    •  TYKERB 1250 mg orally daily throughout the trial + capecitabine 2000 mg/m2/day orally in 2 divided doses, days 1 to 14 in a repeating 21-day cycle (n=198)
    •  Capecitabine 2500 mg/m2/day orally in 2 divided doses, days 1 to 14 in a repeating 21-day cycle (n=201)
  • The primary endpoint was time to progression, considered to be time from randomization until tumor progression or death related to breast cancer1
  • Data were analyzed using both independent (blinded) and investigator radiologic reviews1

Time to Progression

 Time to Progressiona (Independent Assessment)b in the Intent-to-Treat Population1

  • An analysis was performed to measure overall survival, and there was no statistical difference between the groups1
aTime to progression (TTP) was considered to be time from randomization until tumor progression or death related to breast cancer.
bThe time from last tumor assessment to the data cutoff date was >100 days in approximately 30% of patients in the independent assessment. The prespecified assessment interval was 42 or 84 days.
 

Time to Progression (Investigator Assessment) in the Intent-to-Treat Population1

References:

1. Tykerb [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2015.
2. Geyer CE, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355(26):2733-274

INDICATION

TYKERB is indicated in combination with capecitabine for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab.

Limitation of use: Patients should have disease progression on trastuzumab prior to initiation of treatment with TYKERB in combination with capecitabine.

 

IMPORTANT SAFETY INFORMATION

WARNING: Hepatotoxicity has been observed in clinical trials and postmarketing experience. The hepatotoxicity may be severe and deaths have been reported. Causality of the deaths is uncertain.

 

Contraindication: TYKERB is contraindicated in patients with known severe hypersensitivity (eg, anaphylaxis) to this product or any of its components.

Decreased Left Ventricular Ejection Fraction (LVEF): TYKERB has been reported to decrease LVEF. In clinical trials, >57% of LVEF decreases occurred within the first 12 weeks of treatment. Use caution if administering to patients with conditions that could impair LVEF. Confirm normal LVEF before starting TYKERB, and continue evaluations during treatment.

Hepatotoxicity: Hepatotoxicity (alanine transaminase [ALT] or aspartate transaminase [AST] >3 times the upper limit of normal and total bilirubin >2 times the upper limit of normal) has been observed in clinical trials (<1% of patients) and postmarketing experience. The hepatotoxicity may be severe and deaths have been reported. Causality of the deaths is uncertain. The hepatotoxicity may occur days to several months after initiation of treatment. Liver function tests (transaminases, bilirubin, and alkaline phosphatase) should be monitored before initiation of treatment, every 4 to 6 weeks during treatment, and as clinically indicated. If changes in liver function are severe, therapy with TYKERB should be discontinued.

Patients With Severe Hepatic Impairment: If TYKERB is to be administered to patients with severe preexisting hepatic impairment, dose reduction should be considered.

Diarrhea: Diarrhea has been reported during treatment with TYKERB. The diarrhea may be severe, and deaths have been reported. Diarrhea generally occurs early during treatment with TYKERB, with almost half of those patients with diarrhea first experiencing it within 6 days. This usually lasts 4 to 5 days. Lapatinib-induced diarrhea is usually low-grade, with grade 3 and 4 diarrhea occurring in <10% and <1% of patients, respectively. Prompt treatment of diarrhea with antidiarrheal agents (such as loperamide) after the first unformed stool is recommended. Severe cases of diarrhea may require administration of oral or intravenous electrolytes and fluids, use of antibiotics such as fluoroquinolones (especially if diarrhea is persistent beyond 24 hours, there is fever, or grade 3 or 4 neutropenia), and interruption or discontinuation of therapy with TYKERB.

Interstitial Lung Disease/Pneumonitis: TYKERB has been associated with interstitial lung disease and pneumonitis. Patients should be monitored for pulmonary symptoms indicative of interstitial lung disease or pneumonitis. Discontinue TYKERB in patients who experience pulmonary symptoms indicative of greater than or equal to grade 3 interstitial lung disease/pneumonitis.

QT Prolongation: TYKERB prolongs the QT interval in some patients and should be administered with caution in patients who have or may develop QT prolongation, including patients with hypokalemia or hypomagnesemia, congenital long QT syndrome, patients taking cumulative high-dose anthracycline, antiarrhythmics, or other products that lead to QT prolongation. Hypokalemia and hypomagnesemia should be corrected prior to administration, and electrocardiogram and electrolyte monitoring should be considered.

Severe Cutaneous Reactions have been reported. Discontinue TYKERB if life-threatening reactions (eg, erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis) are suspected.

Pregnancy: TYKERB can cause fetal harm when administered to a pregnant woman. Women should be advised not to become pregnant when taking TYKERB. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Adverse Reactions: The most common adverse reactions (≥10%) during therapy with TYKERB plus capecitabine vs capecitabine were diarrhea (65%, 40%), palmar-plantar erythrodysesthesia (53%, 51%), nausea (44%, 43%), rash (28%, 14%), vomiting (26%, 21%), fatigue (23%, 25%), mucosal inflammation (15%, 12%), stomatitis (14%, 11%), pain in extremity (12%, 7%), dyspnea (12%, 8%), back pain (11%, 6%), dyspepsia (11%, 3%), dry skin (10%, 6%), and insomnia (10%, 6%). The most common grade 3 and 4 adverse reactions with TYKERB plus capecitabine compared to capecitabine were diarrhea (14%, 10%) and palmar-plantar erythrodysesthesia (12%, 14%).

Laboratory Abnormalities: Laboratory abnormalities during therapy with TYKERB plus capecitabine vs capecitabine included increased AST (49%, 43%), increased ALT (37%, 33%), and increased total bilirubin (45%, 30%).

 Please see accompanying full Prescribing Information.