Currently Enrolling Trials
Tukysa (tucatinib) - 2 indications
- advanced unresectable or metastatic HER2-positive breast cancer; approved April 2020
- RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer; approved January 2023
Tukysa (tucatinib) is a kinase inhibitor.
Tukysa is specifically 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 antiHER2-based regimens in the metastatic setting.
- 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.
Tukysa is supplied as a tablet for oral administration.
- The recommended dosage of Tukysa is 300 mg taken orally twice daily in combination with trastuzumab and capecitabine (breast cancer) or trastuzumab (colorectal cancer) until disease progression or unacceptable toxicity.
- Advise patients to swallow Tukysa tablets whole and not to chew, crush, or split prior to swallowing. Advise patients not to ingest tablet if it is broken, cracked, or not otherwise intact.
- Advise patients to take Tukysa approximately 12 hours apart and at the same time each day with or without a meal.
- If the patient vomits or misses a dose of Tukysa, instruct the patient to take the next dose at its usual scheduled time.
Mechanism of Action
Tukysa (tucatinib) is a tyrosine kinase inhibitor of HER2. In vitro, tucatinib inhibits phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell proliferation, and showed anti-tumor activity in HER2 expressing tumor cells. In vivo, tucatinib inhibited the growth of HER2 expressing tumors. The combination of tucatinib and trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either drug alone.
Adverse effects associated with the use of Tukysa may include, but are not limited to, the following:
- palmar-plantar erythrodysesthesia
- decreased appetite
- abdominal pain
Indication 1 - advanced unresectable or metastatic HER2-positive breast cancer
approved April 2020
Clinical Trial Results
Indication 2 - RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer
approved January 2023
Clinical Trial Results
Tukysa was approved under the FDA’s Accelerated Approval Program based on tumor response rate and durability of response from the phase 2 MOUNTAINEER clinical trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
MOUNTAINEER evaluated 84 patients with HER2-positive, RAS wild-type, unresectable or metastatic colorectal cancer following previous standard-of-care therapies. Patients evaluated in MOUNTAINEER had not received prior anti-HER2 therapy. Patients received Tukysa (300 mg) twice per day orally in combination with trastuzumab intravenously (8 mg/kg loading dose, then 6 mg/kg every three weeks thereafter) until disease progression or unacceptable toxicity. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR)
Results from the MOUNTAINEER trial showed a 38% overall response rate (ORR) in the patients who received Tukysa in combination with trastuzumab (N=84 with a median age of 55.0 years [range: 24 to 77]). Complete responses were observed in 3.6% of patients (n=3), and partial responses were observed in 35% of patients (n=29). The median duration of response (DOR) per BICR was 12.4 months. At study entry, 64% and 70% of these patients had liver or lung metastases, respectively.