REFRAME YOUR APPROACH
WITH THE TUKYSA REGIMEN*
†Category 1: Based upon high-level evidence (≥1 randomized phase 3 trials or high-quality, robust meta-analyses), there is uniform NCCN consensus (≥85% support of the Panel) that the intervention is appropriate.2
‡Preferred: Interventions that are based on superior efficacy, safety, and evidence; and, when appropriate, affordability.2
NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. See NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for detailed recommendations, including other preferred options.
2L = second line; 3L = third line; HER = human epidermal growth factor receptor; MBC = metastatic breast cancer; NCCN = National Comprehensive Cancer Network.
Proposed MOA
TUKYSA adds another targeted treatment modality to the HER2 treatment approach1
The TUKYSA regimen* includes 3 different MOAs:
- The intracellular HER2 blockade of
TUKYSA1 - The extracellular HER2 blockade and ADCC of
trastuzumab3 - The receptor-independent activity of
capecitabine4
1000x more selective in vitro
TUKYSA is a TKI that is 1000x more selective for HER2 than for EGFR in vitro, which may minimize
off-target
*TUKYSA is indicated in combination with trastuzumab and
ADC = antibody-drug conjugate; ADCC = antibody-dependent cell
cytotoxicity; EGFR = epidermal growth factor receptor; MOA = mechanism of action; T-DM1 =
ado-trastuzumab emtansine; T-DXd = trastuzumab deruxtecan; TKI = tyrosine kinase inhibitor.
Important Safety Information
Warnings and Precautions
-
Diarrhea: TUKYSA can cause severe diarrhea including
dehydration, hypotension, acute kidney injury, and death. 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.
In HER2CLIMB, when TUKYSA was given in combination with trastuzumab and capecitabine, 81% of patients who received TUKYSA experienced diarrhea, including 0.5% with Grade 4 and 12% with Grade 3. 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. -
Hepatotoxicity: TUKYSA can cause severe
hepatotoxicity. 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.
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. - 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 1 week after the last dose.
Adverse Reactions
In HER2CLIMB, serious adverse reactions occurred in 26% of patients
who received TUKYSA; the most common (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; the most common (in ≥1% of patients) were
hepatotoxicity (1.5%) and diarrhea (1%). Adverse reactions led to dose
reduction in 21% of patients who received TUKYSA; the most common (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,
hepatotoxicity, vomiting, stomatitis, decreased appetite, 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 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.
REF-T1K1161
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.
Important Safety Information
Important Safety Information + Indication
Indication
Warnings and Precautions
Warnings and Precautions
-
Diarrhea:
TUKYSA can cause severe diarrhea including dehydration,
hypotension, acute kidney injury, and death. 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.
In HER2CLIMB, when TUKYSA was given in combination with trastuzumab and capecitabine, 81% of patients who received TUKYSA experienced diarrhea, including 0.5% with Grade 4 and 12% with Grade 3. 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. -
Hepatotoxicity:
TUKYSA can cause severe hepatotoxicity. 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.
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.
-
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 1 week after the last dose.
Adverse Reactions
In HER2CLIMB, serious adverse reactions occurred in 26% of
patients who received TUKYSA; the most common (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; the most common (in ≥1% of
patients) were hepatotoxicity (1.5%) and diarrhea (1%). Adverse
reactions led to dose reduction in 21% of patients who received
TUKYSA; the most common (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, hepatotoxicity, vomiting, stomatitis, decreased
appetite, 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 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.
REF-T1K1161
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.
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.
1. TUKYSA. Prescribing information. Seagen Inc.; 2023. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V4.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed April 17, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 3. Trastuzumab. Prescribing information. Genentech, Inc.; 2024. 4. Capecitabine. Prescribing information. Genentech, Inc.; 2022. 5. Kulukian A, Lee P, Taylor J, et al. Preclinical activity of HER2-selective tyrosine kinase inhibitor tucatinib as a single agent or in combination with trastuzumab or docetaxel in solid tumor models. Mol Cancer Ther. 2020;19(4):976-987. doi:10.1158/1535-7163.MCT-19-0873 6. Harandi A, Zaidi AS, Stocker AM, Laber DA. Clinical efficacy and toxicity of anti-EGFR therapy in common cancers. J Oncol. 2009;2009:567486. doi:10.1155/2009/567486 7. Li J. Diarrhea with HER2-targeted agents in cancer patients: a systematic review and meta-analysis. J Clin Pharmacol. 2019;59(7):935-946. doi:10.1002/jcph.1382 8. Rubin I, Yarden Y. The basic biology of HER2. Ann Oncol. 2001;12(suppl 1):S3-S8. doi:10.1093/annonc/12.suppl_1.s3 9. Dent SF, Morse A, Burnette S, Guha A, Moore H. Cardiovascular toxicity of novel HER2-targeted therapies in the treatment of breast cancer. Curr Oncol Rep. 2021;23(11):128. doi:10.1007/s11912-021-01114-x