TUCATINIB TAB

Clinical Criteria Summary

Neurologically unstable Central Nervous System (CNS) metastases requiring urgent local intervention
Unmanageable drug interaction identified
Known pregnancy
Lactating

In combination with trastuzumab and capecitabine for advanced unresectable or metastatic HER2+ breast cancer who received two or more lines of anti-HER2-based therapy in the metastatic setting
In combination with trastuzumab and capecitabine for metastatic HER2+ breast cancer with brain metastases who received one or more lines of anti-HER2-based therapy
In combination with trastuzumab for RAS wild-type HER2+ unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan- based chemotherapy

Care for the oncologic condition provided by VA or VA Community Care oncology provider
Goals of care and role of Palliative Care consult have been discussed and documented
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2

For females who can become pregnant: Pregnancy must be excluded prior to receiving tucatinib
For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during therapy and for one week after stopping treatment

Adult patients with advanced unresectable or metastatic HER2-positive breast cancer
Patients who have received one or more prior anti-HER2-based regimens in the metastatic setting
Includes patients with brain metastases (active brain metastases permitted if urgent local intervention not needed)

Used in combination with trastuzumab and capecitabine
VA formulary guidance: Reserved for patients who have received two or more previous lines of therapy for HER2-positive metastatic breast cancer
Specifically considered as a third-line option for patients who previously received trastuzumab deruxtecan as second-line therapy, particularly those with active brain metastases

Hepatotoxicity monitoring: Monitor ALT, AST, and bilirubin prior to starting tucatinib, every 3 weeks during treatment, and as clinically indicated; interrupt dose, reduce dose, or permanently discontinue based on severity
Diarrhea management: Administer antidiarrheal treatment as clinically indicated; interrupt dose, reduce dose, or permanently discontinue based on severity
Renal function monitoring: Consider alternative markers of renal function if persistent elevations in serum creatinine are observed (due to inhibition of renal tubular secretion without affecting glomerular filtration)

Avoid concomitant use with strong CYP3A inducers or moderate CYP2C8 inducers
Avoid concomitant use with strong CYP2C8 inhibitors; reduce tucatinib dose if concomitant use cannot be avoided
Avoid concomitant use with CYP3A substrates where minimal concentration changes may lead to serious or life-threatening toxicities
Consider reducing the dose of P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities

Pregnancy: Females of reproductive potential should use effective contraception during tucatinib therapy and for ≥1 week after the last dose
Male partners: Males with female partners of reproductive potential should use effective contraception during tucatinib therapy and for ≥1 week after the last dose
Lactation: Breastfeeding is not recommended during tucatinib treatment or for ≥1 week after the last dose due to potential for serious adverse reactions in the breastfed infant