How Do You Manage Sacituzumab Govitecan (SG) Related Adverse Effects?

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Dr. Gupta:
Hello, I'm Dr. Shilpa Gupta, a genitourinary medical oncologist at the Cleveland Clinic Taussig Cancer Institute and I'll talk about how to manage sacituzumab govitecan, or SG, related adverse effects. Let's start with a case presentation. 72-year-old man with metastatic urothelial cancer scheduled to receive his first dose of SG. What pre-medications are recommended to prevent toxicity? Medications to prevent infusion reactions, and medications to prevent chemotherapy-induced nausea and vomiting. In this case, both of these are very important as pre-medications.

Because the SG-related infusion-related reactions can be quite bothersome, the pre-medication recommendations are usually per institution guidelines, specifically Tylenol, diphenhydramine, famotidine, and dexamethasone. For the first infusion, it should be given over three hours and subsequent infusions can be administered over one to two hours if prior infusions were tolerated. Notably, it is important to observe patients during the infusion and for at least 30 minutes after infusions for any signs or symptoms of infusion-related reactions.

The chemotherapy-induced nausea and vomit, the guidelines should be used for sacituzumab govitecan because it's a moderately emetogenic drug. Pre-medication with two or three-drug regimen including 5-HT3 receptor antagonist, corticosteroids, and NK1 receptor antagonist is recommended.

Let's start with a case presentation. A 72-year-old man on SG develops neutropenic fever with ANC of 1,000 and colitis on day seven of cycle one, requiring hospital admission. In this case, we'll withhold SG until patient completely recovers and has an ANC of greater than 1,500, and then resume at 25% dose reduction with empiric growth factors on day eight. In addition, it is recommended to check for UGT1A1.

Neutropenia guidelines are highlighted here. For any grade four neutropenia, greater or than not equal to seven days or grade three febrile neutropenia, or grade three to four neutropenia which delays dosing by two to three weeks for recovery to grade one or less, it's recommended that 25% dose reduction and empiric growth factors be used after the first occurrence. After the second occurrence, reduce the dose by 50%. And if this happens the third time, permanently discontinue treatment. In addition, if at the time of scheduled treatment grade three to four neutropenia which delays dosing beyond three weeks for recovery to grade one or less, one should discontinue treatment because this can be life-threatening, and fatalities have been observed.

As far as concomitant medications, inhibitors of UGT1A1 can increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38 and we should try to run a checklist with a pharmacist. Avoid administering these inhibitors with SG. It's very important to advise patients of the risk of neutropenia and to seek immediate care for chills or other signs of infection. Advise them about the risk of diarrhea and to seek care if they experience diarrhea for the first-time during treatment, GI bleeding, lightheadedness, nausea, or vomiting. Always a good idea to give them Imodium to keep handy in case they develop diarrhea at after hours. Thank you.

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