Two new drugs, tucatinib (Tukysa) and sacituzumab govitecan-hziy (Trodelvy), have been approved by the Food and Drug Administration (FDA) for the treatment of breast cancer. The drugs treat different types of cancer.
Advanced HER2-positive breast cancer. The kinase inhibitor tucatinib has been approved to treat patients with advanced unresectable or metastatic (including those with brain metastasis) human epidermal growth factor receptor 2 (HER2)-positive breast cancer. It is administered orally in combination with trastuzumab (Herceptin) and capecitabine (Xeloda), and is reserved for those who have not benefited from other types of drug therapy.
The efficacy of tucatinib versus placebo (both in combination with trastuzumab and capecitabine) was evaluated in 612 patients in a randomized, double-blind, placebo-controlled clinical trial. Progression-free survival and overall survival improved in patients who received tucatinib compared with those who did not.
Tucatinib carries warnings for severe diarrhea, severe hepatotoxicity, and embryo-fetal toxicity. Severe diarrhea may lead to dehydration, hypotension, acute kidney injury, and death. Severe hepatotoxicity can elevate liver enzymes more than five time the upper limit of normal and bilirubin more than three times the upper limit of normal. The warning for embryo-fetal toxicity is based on risks to the fetus in animal studies.
Serious adverse effects occurred in 26% of patients receiving tucatinib in the clinical trial. The drug's most common adverse effects are diarrhea, palmar-plantar erythrodysesthesia (also known as hand-foot syndrome, which happens when the medication leaks out of capillaries in the palms and soles and damages the tissue), nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash.
Tucatinib is known to have drug interactions with cytochrome P-450 (CYP) 3A and CYP2C8 inducers (drugs that increase the amount of these isoenzymes) and P-glycoprotein substrates. Strong CYP3A inducers or moderate CYP2C8 inducers will decrease the circulating levels of tucatinib, possibly decreasing its effectiveness. Concomitant use should be avoided. CYP3A and P-glycoprotein substrates (drugs that are acted on by these enzymes) will have their circulating levels raised when coadministered with tucatinib, increasing the risk of adverse effects. Avoid concomitant use of tucatinib with CYP3A substrates (which include calcium channel blockers, erythromycin) and consider reduced doses of P-glycoprotein substrates (such as digoxin, cyclosporin) if coadministered with tucatinib.
Prior to patients starting tucatinib, nurses should complete a thorough medication history, and then use a database to see whether any of the patient's current drugs will interact adversely with tucatinib. Nurses should teach patients to swallow tucatinib tablets whole without chewing, crushing, or splitting them. The drug can be taken with or without food. If the patient experiences severe diarrhea or hepatotoxicity, dosage modification is needed. Complete information regarding dose adjustment can be found in the drug's label. Both women and men receiving tucatinib should use effective contraception during drug therapy and for at least one week after the last dose.
Health care providers should report suspected tucatinib-related adverse effects to either the manufacturer (Seattle Genetics at [855] 4Seagen) or the FDA at http://www.fda.gov/medwatch.
For complete prescribing information for tucatinib, see http://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213411s000lbl.pdf.
Triple-negative breast cancer. Sacituzumab govitecan-hziy has been granted accelerated approval for the treatment of triple-negative breast cancer that has metastasized. Patients should have received at least two other therapies without success prior to starting sacituzumab govitecan-hziy. Triple-negative breast cancer is breast cancer that tests negative for estrogen receptors, progesterone receptors, and HER2 protein, and therefore doesn't respond to hormonal therapy or drugs that target HER2. This form of breast cancer accounts for approximately 20% of breast cancers worldwide.
Sacituzumab govitecan-hziy is a monoclonal antibody that targets Trop-2 (transmembrane glycoprotein) receptors, which are responsible for cancer cell growth, division, and spread. It damages the DNA in cancer cells, leading to cell death.
The product's accelerated approval is based on a clinical trial of 108 patients, which found that the drug reduced the size of the tumor in 33.3% of patients. Of the 36 patients with a positive response, a little more than half maintained the response for six months or longer.
Sacituzumab govitecan-hziy carries boxed warnings for the risk of severe neutropenia and severe diarrhea. Other warnings include the risks of hypersensitivity, including anaphylaxis and infusion reactions; nausea/vomiting; neutropenia in those who are homozygous for the uridine diphosphate-glucuronosyl transferase 1A1*28 allele; and embryo-fetal toxicity. The most common adverse effects of sacituzumab govitecan-hziy are nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, decreased appetite, rash, and abdominal pain.
To minimize infusion reactions and nausea and vomiting, the patient should receive premedication consisting of antipyretics, H1 and H2 blockers, and possibly corticosteroids. A two- or three-drug combination should be used to prevent severe nausea and vomiting (such as dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist, and other drugs as indicated). For specific directions related to dose modification in case of infusion reactions or other adverse effects, see the drug's label.
Nurses should administer sacituzumab govitecan-hziy as an IV infusion, never as a push or bolus. The first dose should be infused over three hours and the patient should be observed for allergic responses. Subsequent infusions can be slightly faster, over one to two hours, but the patient must still be closely monitored. If allergic reactions are severe, the drug should be discontinued. Specific information related to reconstitution, dilution, and administration is available in the drug's label.
Nurses should monitor white blood cell count to assess for neutropenia. If the absolute neutrophil count is below 1,500/mm3, or if patients have neutropenic fever, the drug should be withheld. Patients may require pharmacological assistance with granulocyte-colony stimulating factor to stimulate production of white blood cells. Patients who develop febrile neutropenia will also need antiinfective treatment.
Nurses should monitor for diarrhea and ask the provider to order fluids, electrolytes, and antidiarrheal medications if necessary. Atropine is recommended as a first-line treatment, unless contraindicated by other comorbidities. With late diarrhea, the patient should be evaluated for infection. If infection is ruled out, the patient can be treated with loperamide. Severe diarrhea requires sacituzumab govitecan-hziy to be withheld. If the patient develops grade 3 nausea or grade 3 or 4 vomiting, the nurse should withhold the drug and seek antiemetic treatment.
Men and women receiving sacituzumab govitecan-hziy should use effective birth control during drug therapy and until three months after the last dose because of the risk of embryo-fetal toxicity.
For complete prescribing information for sacituzumab govitecan-hziy, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761115s000lbl.pdf.