Gilead sponsored an industry session at the 48th Annual ONS Congress to discuss the clinical considerations and patient counseling talking points surrounding sacituzumab govitecan-hziy (TRODELVY®) for the treatment of metastatic triple-negative breast cancer (mTNBC) and pretreated hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). The session was led by Linda Buck, MSN, MP-C, AOCN-P, of the City of Hope National Medical Center in Newport Beach, California.
In the session, Buck reviewed the unmet needs of patients with these cancers, discussed the efficacy and safety indications of sacituzumab govitecan-hziy, and shared ways to counsel patients who are receiving treatment with sacituzumab govitecan-hziy.
Historically, survival is poor in all subtypes of mBC. The 5-year relative survival is 32% in HR+/HER2- mBC and just 12% in mTNBC. With each line of therapy, treatment effectiveness decreases; first-line therapy maintains efficacy for about 10 months, second line for about 5 months, and by fourth line is roughly 3.5 months. Historically, there is no standard of care or treatment sequence in the postendocrine setting for HR+/HER2- mBC. Chemotherapy is typically the only treatment in mTNBC.
Sacituzumab govitecan-hziy was approved in 2020 for patients with HR+/HER2- unresectable or locally advanced mBC who have received 2 or more prior therapies and at least 1 in the metastatic setting. Further treatment indications were approved in 2023. The drug is the first and only TROP-2-directed antibody-drug conjugate. It is designed with a unique pH-sensitive, hydrolysable linker (CL2A) and a topoisomerase inhibitor payload that acts against TROP-2-expressing cells.
When a patient has reduced UGT1A1 activity, there is an increased risk of adverse reactions, such as neutropenia. It can also cause teratogenicity and/or embryo-fetal lethality when administered in pregnant women, so women should use contraception for 6 months after their last dose, and men given the drug should use prophylactics for 3 months after their last dose. Sacituzumab govitecan-hziy should not be combined with another UGT1A1 inhibitor due to decreased drug metabolization, nor should it be combined with a UGT1A1 inducer because the drug will be metabolized too quickly.
Sacituzumab govitecan-hziy has a lower grade 3/4 adverse reaction profile than single-drug chemotherapy, as demonstrated in the 2 randomized clinical trials, TROPiCS-02 and ASCENT, which both put sacituzumab govitecan-hziy alone against single-drug chemotherapy in the setting of HR+/HER2- mBC and mTNBC, respectively. In the TROPiCS-02 trial, there were no events of interstitial lung disease with sacituzumab govitecan-hziy. Serious adverse events leading to discontinuation were 6% in the TROPiCS-02 study and were similarly low in the ASCENT trial. Notably, no grade 3/4 hair loss was seen, which is an important consideration for many patients.
Roughly 66% of patients will experience neutropenia, diarrhea, and nausea on sacituzumab govitecan-hziy. As a precaution, nurses should already have atropine in their order set, but otherwise patients should be educated on loperamide treatment. Hypersensitivity reactions are possible, but permanent discontinuation due to hypersensitivity is low at 0.2%. Adverse reaction management includes dose modifications for severe neutropenia. Patients should be counseled on the risks and warning signs of neutropenia. They should immediately contact their health care provider if they experience fever, chills, or other infections signs. Patients should be instructed on infection prevention strategies. Diarrhea management includes ruling out infectious causes before giving Imodium. Other adverse reactions can be managed with dose modifications. Doses should never be re-escalated after dose modification due to adverse reactions.
Nurses are in the unique position of having more time with patients, and as such they can develop trust and better communication. Nurses should be aware of the adverse effects and indications because they are able to educate patients on effects and treatments.
Sacituzumab govitecan-hziy should not be administered to pregnant woman; there is no safety information on its use in women who are breastfeeding. As a precaution, lactating patients should discard milk for 1 month after last dose. Sacituzumab govitecan-hziy is not given to babies or children. Patients with moderate or severe hepatic impairment have not been evaluated for safety, but patients with mild hepatic impairment need no adjustment to the starting dose.
Gilead provides sacituzumab govitecan-hziy access support, including reimbursement support, coverage verification, and more.
Buck L; Gilead. Clinical Considerations for the Treatment of mTNBC and HR+/HER2- mBC with an ADC. Industry session. Presented at the 48th Annual ONS Congress; San Antonio, TX, April 26-30, 2023.