Tucatinib, sold under the brand name Tukysa, is an

anticancer medication Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

used for the treatment of HER2-positive breast cancer. It is a small molecule inhibitor of

HER2 Receptor tyrosine-protein kinase erbB-2 is a protein that normally resides in the membranes of cells and is encoded by the ''ERBB2'' gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The ...

. It was developed by Array BioPharma and licensed to Cascadian Therapeutics (formerly Oncothyreon, subsequently part of

Seattle Genetics SeaGen was the world's first large scale commercial tidal stream generator. It was four times more powerful than any other tidal stream generator in the world at the time of installation. It was decommissioned by SIMEC Atlantis Energy Li ...

). Common side effects include diarrhea, palmar-plantar erythrodysesthesia (burning or tingling discomfort in the hands and feet), nausea, fatigue, hepatotoxicity (liver damage), vomiting, stomatitis (inflammation of the mouth and lips), decreased appetite, abdominal pain, headache, anemia and rash. Tucatinib may cause harm to a developing fetus or baby. Tucatinib was approved for medical use in the United States in April 2020, in Australia in August 2020, and in the European Union in February 2021.

Medical uses

Tucatinib is a kinase inhibitor

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

in combination with

trastuzumab Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together ...

and

capecitabine Capecitabine, sold under the brand name Xeloda among others, is a anticancer medication used to treat breast cancer, gastric cancer and colorectal cancer. For breast cancer it is often used together with docetaxel. It is taken by mouth. ...

for the treatment of adults with advanced unresectable or metastatic HER2-positive breast cancer, including those with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. In the European Union, it is indicated in combination with trastuzumab and capecitabine for the treatment of adults with HER2‑positive locally advanced or metastatic breast cancer who have received at least two prior anti‑HER2 treatment regimens. In January 2023, the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) granted accelerated approval to tucatinib in combination with trastuzumab for RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

Clinical trials

Two early stage clinical trials have reported encouraging results, both of which had options to enroll subjects with central nervous system (CNS) metastases. HER2CLIMB is a Phase 2 randomized, double-blinded, placebo-controlled study of tucatinib in combination with

and

in patients with pretreated, unresectable locally advanced or metastatic HER2-positive breast cancer.

History

In April 2020, the U.S.

(FDA) approved tucatinib in combination with chemotherapy (

and

) for the treatment of adults with advanced forms of HER2-positive breast cancer that can't be removed with surgery, or has spread to other parts of the body, including the brain, and who have received one or more prior treatments. The FDA collaborated with the Australian

Therapeutic Goods Administration The Therapeutic Goods Administration (TGA) is the medicine and therapeutic regulatory agency of the Australian Government. As part of the Department of Health, Disability and Ageing, the TGA regulates the safety, quality, efficacy and advertisi ...

(TGA),

Health Canada Health Canada (HC; )Health Canada is the applied title under the Federal Identity Program; the legal title is Department of Health (). is the Structure of the Canadian federal government#Departments, with subsidiary units, department of the Gove ...

Health Sciences Authority The Health Sciences Authority (HSA) is a statutory board under the Ministry of Health of the Government of Singapore. It is a multi-disciplinary agency responsible for applying medical, pharmaceutical, and scientific expertise to protect and ...

(HSA, Singapore) and

Swissmedic The Swiss Agency for Therapeutic Products (Swissmedic) is the Swiss surveillance authority for medicines and medical devices, registered in Bern. It began operations on 1 January 2002 as successor of ''Interkantonale Kontrollstelle für Heilmittel ...

(SMC, Switzerland) on the review. This was the first Project Orbis partnership between the FDA, HSA and Swissmedic. , the application is still under review at the other agencies. Tucatinib is a

kinase inhibitor In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...

meaning it blocks a type of enzyme (kinase) and helps prevent the cancer cells from growing. Tucatinib is approved for treatment after adults have taken one or more anti-HER2-based regimens in the metastatic setting. The FDA approved tucatinib based on the results of the HER2CLIMB trial (NCT02614794) enrolling 612 subjects who had HER2-positive advanced unresectable or

metastatic breast cancer Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumors, secondaries or stage IV breast cancer, is a stage of breast cancer where the breast cancer cells have spread to distant sites beyond the axillary l ...

and had prior treatment with

pertuzumab Pertuzumab, sold under the brand name Perjeta, is a monoclonal antibody used in combination with trastuzumab and docetaxel for the treatment of metastatic HER2-positive breast cancer; it also used in the same combination as a neoadjuvant in earl ...

and

ado-trastuzumab emtansine Trastuzumab emtansine, sold under the brand name Kadcyla, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the cytotoxic agent DM1. Trastuzumab alone stops growth of c ...

(T-DM1). Subjects with previously treated and stable brain metastases, as well as those with previously treated and growing or untreated brain metastases, were eligible for the clinical trial, and 48% of enrolled subjects had brain metastases at the start of the trial. Subjects received either tucatinib 300mg twice daily plus trastuzumab and capecitabine (tucatinib arm, n=410) or placebo plus trastuzumab and capecitabine (control arm, n=202). The primary endpoint was progression-free survival (PFS), or the amount of time when there was no growth of the tumor, assessed by a blinded independent central review, evaluated in the initial 480 randomized patients. The median PFS in subjects who received tucatinib, trastuzumab, and capecitabine was 7.8 months (95% CI: 7.5, 9.6) compared to 5.6 months (95% CI: 4.2, 7.1) in those subjects who received placebo, trastuzumab, and capecitabine (HR 0.54; 95% CI: 0.42, 0.71; p<0.00001). Overall survival and PFS in subjects with brain metastases at baseline were key secondary endpoints. The median overall survival in subjects who received tucatinib, trastuzumab, and capecitabine was 21.9 months (95% CI: 18.3, 31.0) compared to 17.4 months (95% CI: 13.6, 19.9) in subjects who received placebo, trastuzumab, and capecitabine (HR: 0.66; 95% CI: 0.50, 0.87; p=0.00480). The median PFS in subjects with brain metastases at baseline who received tucatinib, trastuzumab and capecitabine was 7.6 months (95% CI: 6.2, 9.5) compared to 5.4 months (95% CI: 4.1, 5.7) in subjects who received placebo, trastuzumab and capecitabine (HR: 0.48; 0.34, 0.69; p<0.00001). The FDA granted the application for tucatinib

priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

breakthrough therapy Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "b ...

fast track Fast Track, Fast track, or Fasttrack may refer to: Processes and systems * Fast track (FDA), a U.S. Food and Drug Administration expedited review program * Fast track (trade), the authority of the U.S. President to broker trade agreements with lim ...

, and

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

designations. The FDA granted approval of Tukysa to Seattle Genetics, Inc.

Society and culture

Economics

Tucatinib was denied entry into the Australian

Pharmaceutical Benefits Scheme The Pharmaceutical Benefits Scheme (PBS) is a program of the Australian Government that subsidises prescription medication for Australian citizens and permanent residents, as well as international visitors covered by a reciprocal health car ...

in March 2021, as "the incremental cost effectiveness ratio was unacceptably high at the proposed price".

Legal status

Tucatinib was approved for medical use in the United States in April 2020. Tucatinib was approved for medical use in Australia in August 2020. On 10 December 2020, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...

(CHMP) of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Tukysa, intended for the treatment of HER2-positive locally advanced or metastatic breast cancer. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. The applicant for this medicinal product is Seagen B.V. Tucatinib was approved for medical use in the European Union in February 2021.

Names

Tucatinib is the International nonproprietary name.

References

External links

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