In patients with metastatic colorectal cancer
ARE YOU TESTING FOR RAS AND HER2 (ERBB2) STATUS?
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.1,2
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend testing for RAS and BRAF mutations and HER2 amplification in patients with metastatic colorectal cancer.1,2
Testing for all actionable biomarkers should be initiated as early as possible to help guide treatment decisions, according to ASCO guidelines.3
OPTIONS FOR HER2 TESTING
Immunohistochemistry (IHC)
IHC measures the number of HER2 receptors on the surface of cells. An IHC score of 3+ or an IHC score of 2+ with ISH+ confirmation indicates HER2 overexpression.4
In situ hybridization (ISH)
ISH measures the number of copies of the HER2 gene present in a cell and can be used to identify HER2 amplification. ISH is typically used to help confirm the HER2 status of IHC 2+ tumors.4
Next-generation sequencing (NGS)
NGS can detect a multitude of variations and mutations in a cell, including HER2 amplification.5,6
However, it’s important to note that not all NGS panels include HER2 amplification by default.5,6
- Select patients for treatment of unresectable or metastatic colorectal cancer with TUKYSA based on the presence of HER2 overexpression or gene amplification, and RAS WT7
- An FDA-approved test for the detection of HER2 overexpression and gene amplification in patients with unresectable or metastatic colorectal cancer is not currently available. Information on FDA-approved tests for the detection of RAS mutations in patients with unresectable or metastatic colorectal cancer is available at http://www.fda.gov/CompanionDiagnostics7
The TUKYSA® (tucatinib) regimen may be an appropriate treatment option for eligible patients with RAS WT, HER2+ mCRC
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.
ASCO = American Society of Clinical Oncology; FDA = US Food and Drug Administration; HER = human epidermal growth factor receptor; mCRC = metastatic colorectal cancer; NCCN = National Comprehensive Cancer Network; WT = wild type.
Select Important Safety Information
Warnings and Precautions
- 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.
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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. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V2.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed May 2, 2023. 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. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer V3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed June 5, 2023. 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. Sepulveda AR, Hamilton SR, Allegra CJ, et al. Molecular biomarkers for the evaluation of colorectal cancer: guideline from the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology. Arch Pathol Lab Med. 2017;141(5):625-657. doi:10.5858/arpa.2016-0554-CP 4. Furrer D, Sanschagrin F, Jacob S, Diorio C. Advantages and disadvantages of technologies for HER2 testing in breast cancer specimens. Am J Clin Pathol. 2015;144(5):686-703. doi:10.1309/AJCPT41TCBUEVDQC 5. Mosele F, Remon J, Mateo J, et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2020;31(11):1491-1505. doi:10.1016/j.annonc.2020.07.014 6. Jennings LJ, Arcila ME, Corless C, et al. Guidelines for validation of next-generation sequencing–based oncology panels: a joint consensus recommendation of Association for Molecular Pathology and College of American Pathologists. J Mol Diagn. 2017;19(3):341-365. doi:10.1016/j.jmoldx.2017.01.011 7. TUKYSA [Prescribing Information]. Bothell, WA: Seagen Inc. January 2023.