Managing TNBC

CE / CME

Cases and Challenges in the Optimal Treatment of Triple-Negative BC

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

Nurse Practitioners: 1.00 Nursing contact hours, includes 1.00 hour of pharmacotherapy credit

Released: May 08, 2023

Expiration: May 07, 2024

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Toxicity Management With T-DXd and PARP Inhibitors

Management of Toxicities of T-DXd
Overall, the side effects of T-DXd are manageable, and include hematologic and gastrointestinal toxicities, which were reported in 30% or more of patients. Frequent all-grade side effects of T-DXd include nausea, diarrhea, vomiting, and constipation, each of which is fairly common. However, the rate of grade ≥3 toxicities is low, and includes nausea (4.8%) and diarrhea (2.4%).42 Two important side effects of concern are cardiotoxicity, including left-ventricular dystrophy (4.6%) and ILD, which can be fatal if missed. In DESTINY-Breast04, ILD occurred in 12.1% of patients treated with T-DXd, including 1.3% grade 3 and 0.8% grade 5, with a median time to onset of 129 days. When managing patients treated with T-DXd, it is important to be alert to symptoms of ILD, such as cough or dyspnea (Figure 4). Patients should have complete blood count and left ventricular ejection fraction evaluation prior to starting treatment and at regular intervals while on therapy. Premedication with antiemetics can limit incidence or severity of nausea/vomiting associated with the cytotoxic component of the ADC.10,41,49

Figure 4. Management of ILD associated with T-DXd.42,49  

 

Expert Insights From Dr Force:Detecting ILD in Patients Receiving T-DXd

 

Management of Toxicities with PARP Inhibitors
Hematologic and gastrointestinal toxicities are frequent with all PARP inhibitors. Patients should be monitored for anemia, neutropenia, and thrombocytopenia, which tend to develop within 3-4 months of starting treatment and usually resolve within a few weeks. High-grade anemia is the most frequent side effect with these drugs. Transfusion may be needed for symptomatic anemia or hemoglobin <7 g/dL. Grade 1 or 2 nausea is common, and other gastrointestinal toxicity can be managed as is done for chemotherapy-induced symptoms (eg, antiemetics or antidiarrheals). Renal function should be monitored on treatment; elevated serum creatinine related to treatment may not reflect diminished function and treatment can often be continued. Alopecia may occur, but generally has a later onset than with chemotherapy, peaking at about 5 months. Fatigue with treatment should be managed with nonpharmacologic interventions if possible.50,51 Increases in cholesterol and liver enzymes may occur and should be managed. Dose reductions are used to manage nonhematologic toxicities; if grade 3 or 4 toxicity persists for ≥28 days despite this, treatment should be discontinued.50,52 Less common toxicities include neurologic effects, mostly mild photosensitivity reactions (although more severe rash has been reported), and dyspnea or cough.50,51

 

Expert Insights From Dr Force:Close Monitoring of Myelosuppression in Patients Receiving PARP Inhibitors