In HER2 + MBC following 1L progression and beyond*

EMBRACE SUPERIOR SURVIVAL WITH PROVEN SAFETY

TUKYSA + trastuzumab + capecitabine vs placebo + trastuzumab + capecitabine

More than 2 years median overall survival at follow up analysis2

Follow-up OS analysis: Results of this prespecified exploratory analysis are descriptive but not conclusive, are not controlled for type 1 error, and should be interpreted with caution.

Safe and well tolerated1,3

Explore survival data See safety profile View the 2 Year Follow-up Analysis

Study design: HER2CLIMB was a randomized (2:1) trial of TUKYSA or placebo each in combination with trastuzumab and capecitabine in 612 patients with HER2+ MBC, previously treated with trastuzumab, pertuzumab, and T-DM1. Primary endpoint was PFS per BICR in the first 480 patients enrolled. Secondary endpoints included OS. A prespecified exploratory analysis was included to evaluate OS at ~2 years. Learn more about the trial design.

*≥1 anti-HER2-based regimen in the metastatic setting.1 †Data from the first 480 patients. ‡Primary analysis (data cutoff: September 4, 2019).3 §Prespecified exploratory analysis (data cutoff: February 8, 2021).2



The only FDA-approved 2L+ treatment option to demonstrate a significant OS benefit in patients with HER2+ MBC who received prior trastuzumab, pertuzumab, and T-DM11,4-7

Dosing

Administering the TUKYSA regimen

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Warnings and Precautions

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CI = confidence interval; HER = human epidermal growth factor receptor; HR = hazard ratio; MBC = metastatic breast cancer; OS = overall survival; PFS = progression-free survival; T-DM1 = ado-trastuzumab emtansine; PPE = palmar-plantar erythrodysesthesia

Discover how TUKYSA selectively blocks HER2 signaling to, together with trastuzumab, trigger tumor cell death1,16

Important Safety Information

Warnings and Precautions

  • Diarrhea: TUKYSA can cause severe diarrhea including dehydration, hypotension, acute kidney injury, and death. In HER2CLIMB, 81% of patients who received TUKYSA experienced diarrhea, including 12% with Grade 3 and 0.5% with Grade 4. Both patients who developed Grade 4 diarrhea subsequently died, with diarrhea as a contributor to death. Median time to onset of the first episode of diarrhea was 12 days and the median time to resolution was 8 days. Diarrhea led to TUKYSA dose reductions in 6% of patients and TUKYSA discontinuation in 1% of patients. Prophylactic use of antidiarrheal treatment was not required on HER2CLIMB.

    If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the severity of the diarrhea, interrupt dose, then dose reduce or permanently discontinue TUKYSA.

  • Hepatotoxicity: TUKYSA can cause severe hepatotoxicity. In HER2CLIMB, 8% of patients who received TUKYSA had an ALT increase >5 × ULN, 6% had an AST increase >5 × ULN, and 1.5% had a bilirubin increase >3 × ULN (Grade ≥3). Hepatotoxicity led to TUKYSA dose reductions in 8% of patients and TUKYSA discontinuation in 1.5% of patients.

    Monitor ALT, AST, and bilirubin prior to starting TUKYSA, every 3 weeks during treatment, and as clinically indicated. Based on the severity of hepatotoxicity, interrupt dose, then dose reduce or permanently discontinue TUKYSA.

  • Embryo-Fetal Toxicity: TUKYSA can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential, and male patients with female partners of reproductive potential, to use effective contraception during TUKYSA treatment and for at least 1 week after the last dose.

Adverse Reactions

Serious adverse reactions occurred in 26% of patients who received TUKYSA; those occurring in ≥2% of patients were diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), and seizure (2%). Fatal adverse reactions occurred in 2% of patients who received TUKYSA including sudden death, sepsis, dehydration, and cardiogenic shock.

Adverse reactions led to treatment discontinuation in 6% of patients who received TUKYSA; those occurring in ≥1% of patients were hepatotoxicity (1.5%) and diarrhea (1%). Adverse reactions led to dose reduction in 21% of patients who received TUKYSA; those occurring in ≥2% of patients were hepatotoxicity (8%) and diarrhea (6%).

The most common adverse reactions in patients who received TUKYSA (≥20%) were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash.

Lab Abnormalities

In HER2CLIMB, Grade ≥3 laboratory abnormalities reported in ≥5% of patients who received TUKYSA were decreased phosphate, increased ALT, decreased potassium, and increased AST.

The mean increase in serum creatinine was 32% within the first 21 days of treatment with TUKYSA. The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed.

Drug Interactions

  • Strong CYP3A/Moderate CYP2C8 Inducers: Concomitant use may decrease TUKYSA activity. Avoid concomitant use of TUKYSA.
  • Strong or Moderate CYP2C8 Inhibitors: Concomitant use of TUKYSA with a strong CYP2C8 inhibitor may increase the risk of TUKYSA toxicity; avoid concomitant use. Increase monitoring for TUKYSA toxicity with moderate CYP2C8 inhibitors.
  • CYP3A Substrates: Concomitant use may increase the toxicity associated with a CYP3A substrate. Avoid concomitant use of TUKYSA where minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, decrease the CYP3A substrate dosage.
  • P-gp Substrates: Concomitant use may increase the toxicity associated with a P-gp substrate. Consider reducing the dosage of P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicity.

Use in Specific Populations

  • Lactation: Advise women not to breastfeed while taking TUKYSA and for at least 1 week after the last dose.
  • Renal Impairment: Use of TUKYSA in combination with capecitabine and trastuzumab is not recommended in patients with severe renal impairment (CLcr < 30 mL/min), because capecitabine is contraindicated in patients with severe renal impairment.
  • Hepatic Impairment: Reduce the dose of TUKYSA for patients with severe (Child-Pugh C) hepatic impairment.

Indication

TUKYSA is indicated in combination with trastuzumab and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.

Please see full Prescribing Information.

References