In combination with trastuzumab + capecitabine

TUKYSA extended survival for patients with HER2+ MBC1

HER2CLIMB met all key efficacy endpoints1

In patients treated with TUKYSA + trastuzumab + capecitabine (TUKYSA arm) vs those treated with placebo + trastuzumab + capecitabine (control arm):

Primary endpoint

  • 46% reduction in the risk of disease progression or death in the primary endpoint population (n = 480; HR = 0.54 [95% CI: 0.42-0.71], P <0.00001; median PFS: 7.8 months [95% CI: 7.5-9.6] in the TUKYSA arm vs 5.6 months [95% CI: 4.2-7.1] in the control arm)

Secondary endpoints

  • 4.5-month improvement in median OS (21.9 months [95% CI: 18.3-31.0] in the TUKYSA arm vs 17.4 months [95% CI: 13.6-19.9] in the control arm; HR = 0.66 [95% CI: 0.50-0.87], P = 0.0048)
  • 52% lower risk of disease progression or death in patients with brain metastases (HR = 0.48 [95% CI: 0.34-0.69], P <0.00001; median PFS: 7.6 months [95% CI: 6.2-9.5] in the TUKYSA arm vs 5.4 months [95% CI: 4.1-5.7] in the control arm)
  • ~2x greater antitumor activity (confirmed ORR: 40.6% in the TUKYSA arm [n = 340; CR = 0.9%; PR = 39.7%; 95% CI: 35.3-46.0] vs 22.8% in the control arm [n = 171; CR = 1.2%; PR = 21.6%; 95% CI: 16.7-29.8]; P = 0.00008)

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.

See full survival data below.

Learn about the HER2CLIMB trial design and baseline patient characteristics.


CI = confidence interval; CR = complete response; HR = hazard ratio; HER = human epidermal growth factor receptor; MBC = metastatic breast cancer; PFS = progression-free survival; PR = partial response; ORR = objective response rate; OS = overall survival.

In combination with trastuzumab + capecitabine

TUKYSA improved OS in the total population*1

TUKYSA (tucatinib): Kaplan-Meier estimates of overall survival (OS) from the HER2CLIMB trial TUKYSA (tucatinib): Kaplan-Meier estimates of overall survival (OS) from the HER2CLIMB trial

Secondary endpoint

HR = 0.66 (95% CI: 0.55-0.87); P = 0.0048

Number of Events

TUKYSA arm: 130/410
Control arm: 85/202

At 24 months, more than 1.5x as many patients were alive†2

TUKYSA arm, 45% vs control arm, 27%

*Time from randomization to death from any cause.

†This exploratory analysis is descriptive only. HER2CLIMB was not powered to assess a statistical difference between treatment groups at this time point.

Consistent OS across all subgroups2

Forest plot of the OS subgroup analysis Forest plot of the OS subgroup analysis

‡These subgroups were not prespecified and results of the exploratory analysis should be interpreted with caution.
§Data from the patients in the United States and Canada were combined for this analysis.
ECOG = Eastern Cooperative Oncology Group; ER = estrogen receptor; PR = progesterone receptor.

In combination with trastuzumab + capecitabine

TUKYSA delivered proven PFS benefit in patients with and without brain metastases1-3

Reduced risk of disease progression or death by 46% in the primary endpoint population1

Kaplan-Meier estimates of PFS in the primary endpoint population (primary endpoint) from the HER2CLIMB trial Kaplan-Meier estimates of PFS in the primary endpoint population (primary endpoint) from the HER2CLIMB trial

Primary endpoint

HR = 0.54 (95% CI: 0.42-0.71); P <0.00001

Number of Events

TUKYSA arm: 178/320
Control arm: 97/160

At 12 months, ~3x as many patients were progression-free**2

TUKYSA arm, 33% vs control arm, 12%

**This exploratory analysis is descriptive only. HER2CLIMB was not powered to assess a statistical difference between treatment groups at this time point.

Reduced risk of disease progression or death by 52% in patients with brain metastases††1,2

Kaplan-Meier estimates of PFS in patients with brain metastases (secondary endpoint) from the HER2CLIMB trial Kaplan-Meier estimates of PFS in patients with brain metastases (secondary endpoint) from the HER2CLIMB trial

Secondary endpoint

HR = 0.48 (95% CI: 0.34-0.69); P <0.00001

Number of Events

TUKYSA arm: 106/198
Control arm: 51/93

At 12 months, 1 in 4 patients with brain metastases were progression-free‡‡2

TUKYSA arm, 25% vs control arm, 0%

††Analysis includes patients with history or presence of parenchymal brain metastases at baseline, including target and nontarget lesions. Analysis does not include patients with dural lesions only.

‡‡This exploratory analysis is descriptive only. HER2CLIMB was not powered to assess a statistical difference between treatment groups at this time point.

Reduced risk of disease progression or death by 43% in patients without brain metastases§§3

Kaplan-Meier estimates of PFS in patients without brain metastases (exploratory endpoint) from the HER2CLIMB trial Kaplan-Meier estimates of PFS in patients without brain metastases (exploratory endpoint) from the HER2CLIMB trial

Exploratory endpoint

HR = 0.57 (95% CI: 0.41-0.80)

Number of Events

TUKYSA arm: 91/211
Control arm: 60/108

§§This exploratory analysis was not controlled for a type 1 error and HER2CLIMB was not powered to test this endpoint. Results are descriptive only and are not contained in the approved product labeling.

¶Time from randomization to documented disease progression, as assessed by blinded independent central review, or death from any cause.

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 hepatoxicity, 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

  • 1. TUKYSA [Prescribing Information]. Bothell, WA: Seattle Genetics, Inc. April 2020.
  • 2. Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597-609.
  • 3. Murthy RK, Loi S, Okines A, et al. Supplemental appendix for: Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597-609.