For:
HR+, HER2+ Metastatic Breast Cancer (mBC)

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.

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Indication TYKERB® (lapatinib) tablets is indicated in combination with letrozole for the treatment of postmenopausal women with hormone-receptor positive metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated.

TYKERB in combination with an aromatase inhibitor has not been compared to a trastuzumab-containing chemotherapy regimen for the treatment of metastatic breast cancer.

EFFICACY

Trial Design

EFG 30008: A large multicenter, phase 3, randomized, double-blind, controlled trial of 1286 postmenopausal women with hormone receptor-positive metastatic breast cancer1,2

  • 219 (17%) were HER2+
  • 952 (74%) were HER2-
  • 115 (9%) did not have their HER2 receptor status confirmed

 

Abbreviations: ER+, estrogen receptor-positive; HER2+, human EGF (epidermal growth factor) receptor 2-positive; HER2-ve, human EGF (epidermal growth factor) receptor 2-negative; PgR+, progesterone receptor-positive.
PFS was defined as the interval of time between date of randomization and the earlier date of first documented sign of disease progression or death due to any cause.

 

  • Approximately 50% of the HER2-positive population had prior adjuvant/neo-adjuvant chemotherapy and 56% had prior hormonal therapy1
  • Only 2 patients had prior trastuzumab. However, trastuzumab was not approved for adjuvant use at the time of the study initiation1,2

Patient Baseline Characteristics

Baseline Characteristics in HR+/HER2+ Subgroup1,2

 

  • Patient baseline characteristics were similar between the 2 groups1,2 

Primary End Point

Progression-Free Survival for the HER2+ Population1

4.3 weeks = 1 month.
  • There was a significant increase in response rate for TYKERB® (lapatinib) Tablets + letrozole (27.9% [95% CI; 19.8, 37.2]) compared to letrozole (14.8% [95% CI; 8.7, 22.9]), (odds ratio [OR] = 0.4 [95% CI; 0.2, 0.9; P=0.021])1,2
  • At the time of updated analysis, the overall survival data were not mature1

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.

 

No significant improvement in PFS in the HER2- population1

  • There was no statistical significance in median PFS for TYKERB + letrozole vs letrozole in the HER2- subgroup
  • Median PFS was 59.7 weeks (95% CI; 48.6, 69.7) in the TYKERB + letrozole group compared to 58.3 weeks in the letrozole group (95% CI; 47.9, 62.0); HR=0.90 (95% CI: 0.77, 1.05); P=0.188
  • Response rates were 32.6% (95% CI; 28.4, 37.0) in the TYKERB + letrozole group and 31.6% in the letrozole group (95% CI; 27.5, 36.0)

References:

1. Tykerb [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2018.
2. Johnston S, Pippen J Jr, Pivot X, et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009;27(33):5538-5546.

INDICATION

TYKERB® (lapatinib) tablets is indicated in combination with letrozole for the treatment of postmenopausal women with hormone-receptor positive metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated.

TYKERB in combination with an aromatase inhibitor has not been compared to a trastuzumab-containing chemotherapy regimen for the treatment of metastatic breast cancer.

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 (ULN) and total bilirubin >2 times the ULN] 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 and patients should not be retreated with TYKERB.

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: A concentration-dependent QT prolongation has been associated with TYKERB. During treatment with TYKERB, monitor 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 with known risk for QT prolongation/Torsades de Pointes. Correct hypokalemia or hypomagnesemia prior to TYKERB administration.

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. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Prior to the initiation of TYKERB, verify the pregnancy status of females of reproductive potential and advise them to use effective contraception during treatment with TYKERB and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TYKERB and for 1 week after the last dose.

Adverse Reactions: The most common adverse reactions (≥10%) during therapy with TYKERB plus letrozole compared to letrozole were diarrhea (64%, 20%), rash (44%, 13%), nausea (31%, 21%), fatigue (20%, 17%), vomiting (17%, 11%), headache, (14%, 13%), dry skin (13%, 4%), alopecia (13%, 7%), pruritus (12%, 9%), asthenia (12%, 11%), nail disorder (11%, <1%), anorexia (11%, 9%) and epistaxis (11%, 2%).The most common (≥2%) grade 3 and 4 adverse reactions with TYKERB plus letrozole compared to letrozole were diarrhea (9%, <1%) and fatigue (2%, <1%).

Laboratory Abnormalities: Laboratory abnormalities during therapy with TYKERB plus letrozole compared to letrozole included increased AST (53%, 36%), increased ALT (46%, 35%), and increased total bilirubin (22%, 11%).

Please see accompanying full Prescribing Information, including Boxed WARNING.