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In 2L+ RAS WT, HER2+ mCRC

IT'S TIME TO REINVENT WHAT'S POSSIBLE

The TUKYSA regimen is the first FDA-approved HER2-directed therapy in 2L+ RAS WT, HER2+ mCRC1,2*

*TUKYSA is indicated in combination with trastuzumab.1

National Comprehensive Cancer Network® (NCCN®) Recommended 
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend testing for RAS and BRAF mutations and HER2 amplification in patients with metastatic colorectal cancer.3,4


2L = second-line; FDA = US Food and Drug Administration; HER = human epidermal growth factor receptor; mCRC = metastatic colorectal cancer; NCCN = National Comprehensive Cancer Network; WT = wild type.

Biomarker Testing

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Testing for RAS and HER2 status

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Dosing

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Administering the TUKYSA® (tucatinib) regimen

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Access

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Seagen Secure® for patient support

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TUKYSA is part of a chemotherapy-free treatment option designed to target HER2+ mCRC1,5*

Vertical inhibition

Vertical inhibition may be achieved through complementary intracellular and extracellular targeting by TUKYSA and trastuzumab, respectively. This vertical inhibition has shown a greater antitumor effect in preclinical studies, compared to inhibition by either product alone.1,6

*HER2 may also be expressed on healthy cells, which may also be targeted by anti-HER2 treatments. This may result in adverse reactions, some of which may be serious.7,8

Depiction of TUKYSA® (tucatinib) tablets Mechanism of Action 

 

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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 MOUNTAINEER, when TUKYSA was given in combination with trastuzumab, diarrhea occurred in 64% of patients, including Grade 3 (3.5%), Grade 2 (10%), and Grade 1 (50%). 
  • 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 MOUNTAINEER, 6% of patients had a bilirubin increase > 3 × ULN (Grade ≥3), 6% had an AST increase > 5 × ULN, and 4.7% had an ALT increase > 5 × ULN. Hepatotoxicity led to dose reduction of TUKYSA in 3.5% of patients and discontinuation of TUKYSA in 2.3% 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

Serious adverse reactions occurred in 22% of patients; the most common (in ≥2% of patients) were intestinal obstruction (7%), urinary tract infection (3.5%), pneumonia, abdominal pain, and rectal perforation (2.3% each).

Adverse reactions leading to permanent discontinuation of TUKYSA occurred in 6% of patients; the most common (in ≥2% of patients) was increased ALT (2.3%). Adverse reactions leading to dosage interruption occurred in 23% of patients; the most common (in ≥3% of patients) were increased ALT and diarrhea (3.5% each). Adverse reactions leading to dose reduction occurred in 9% of patients; the most common (in ≥2% of patients) were increased ALT and diarrhea (2.3% each).

The most common adverse reactions (≥20%) in patients treated with TUKYSA and trastuzumab were diarrhea, fatigue, rash, nausea, abdominal pain, infusion-related reactions, and pyrexia.

Other adverse reactions (<10%) include epistaxis (7%), weight decreased (7%), oropharyngeal pain (5%), oral dysesthesia (1%), and stomatitis (1%).

Lab Abnormalities

In MOUNTAINEER, Grade ≥3 laboratory abnormalities reported in ≥5% of patients who received TUKYSA were decreased lymphocytes, decreased sodium, increased AST, and increased bilirubin.

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 in 87% of patients with values outside normal lab limits 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 with a CYP3A substrate, 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 toxicities.

Use in Specific Populations

  • Lactation: Advise women not to breastfeed while taking TUKYSA and for 1 week after the last dose.
  • Hepatic Impairment: Reduce the dose of TUKYSA for patients with severe (Child-Pugh C) hepatic impairment.

REF-7647_FINAL_01/23

Indication

TUKYSA is indicated in combination with trastuzumab for the treatment of adult patients with RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Please see full Prescribing Information.

References 1. TUKYSA [Prescribing Information]. Bothell, WA: Seagen Inc. January 2023. 2. Strickler JH, Cercek A, Siena S, et al; MOUNTAINEER investigators. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study. Lancet Oncol. 2023;24(5):496-508. doi:10.1016/S1470-2045(23)00150-X 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V4.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed July 11, 2024. 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. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer V3.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed July 11, 2024. 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. 5. Trastuzumab [Prescribing Information]. South San Francisco, CA: Genentech, Inc. February 2021. 6. 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 7. 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 8. 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


Important Safety Information and Indication

Find Out More+

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 MOUNTAINEER, when TUKYSA was given in combination with trastuzumab, diarrhea occurred in 64% of patients, including Grade 3 (3.5%), Grade 2 (10%), and Grade 1 (50%). 
  • 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 MOUNTAINEER, 6% of patients had a bilirubin increase > 3 × ULN (Grade ≥3), 6% had an AST increase > 5 × ULN, and 4.7% had an ALT increase > 5 × ULN. Hepatotoxicity led to dose reduction of TUKYSA in 3.5% of patients and discontinuation of TUKYSA in 2.3% of patients.