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Safety of ADCs in MBC: Module

CME

Optimizing Outcomes and Quality of Life for Patients With Advanced Breast Cancer Through Effective Management of ADC-Associated Toxicities

Physicians: Maximum of 0.75 AMA PRA Category 1 Credit™

Released: February 07, 2024

Expiration: February 06, 2025

Komal Jhaveri
Komal Jhaveri, MD, FACP
CME/CE Information

Activity

Progress
1 2
Course Completed

TROPiCS-02 Trial of SG vs Chemotherapy: Safety Summary

In the phase III TROPiCS-02 trial of SG vs chemotherapy of physician’s choice for previously treated patients with HR-positive/HER2-negative metastatic breast cancer, 74% of patients who received SG experienced grade ≥3 TEAEs compared with 60% of patients who received chemotherapy.8 Treatment was discontinued in 6% of patients who received SG vs 4% of patients who received chemotherapy. TEAEs led to dose delays and dose reductions in 66% and 34% of patients, respectively, who received SG vs 44% and 33% of patients, respectively, who received chemotherapy. The most common serious TEAEs associated with SG were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), and neutropenic colitis (2%). On the chemotherapy arm, serious TEAEs included febrile neutropenia (4%), pneumonia (2%), nausea (2%), and dyspnea (2%). Treatment with SG led to the death of 1 patient vs none on the chemotherapy arm.

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Treatment‑Related AEs With SG

In the phase III ASCENT trial of SG vs physician’s choice of chemotherapy for patients with relapsed/refractory metastatic triple-negative breast cancer, the AEs of special interest associated with SG were neutropenia and diarrhea, and these events are expected because of its SN-38 cytotoxic payload.3,18-20 More patients who received SG experienced neutropenia compared with those who received chemotherapy. The most common grade 1/2 SG-related AEs were nausea, diarrhea, alopecia, and fatigue. Neutropenia was the most common grade 3/4 AE associated with SG.

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Management of Common and Potentially Severe Toxicities Associated With SG

Of note, severe or life-threatening neutropenia may occur with SG. The UGT1A1*28 genotype should be suspected if neutropenia is prolonged and unresponsive to treatment.18,20,21 For a patient with an ANC <1500/mm3 on Day 1 of any cycle or ANC <1000/mm3 on Day 8 of any cycle, SG should be withheld.3,21 Also, for patients with neutropenic fever, SG should be withheld. If grade 4 neutropenia persists for ≥7 days or if grade 3/4 febrile neutropenia develops, the dose of SG should be reduced, and G-CSF be administered.3 If grade ≥3 neutropenia occurs for a third time, treatment should be discontinued, and G-CSF should be administered. If grade 3/4 neutropenia that delays dosing for >3 weeks occurs at the time of scheduled treatment, SG treatment should be discontinued, and G-CSF should be administered.

SG may cause severe diarrhea. Per the prescribing information, SG should be withheld for grade 3/4 diarrhea at the time of scheduled treatment and resumed after resolution to grade ≤1. It is important to educate patients about antidiarrhea medications as soon as the first event of diarrhea is experienced. Patients also should be educated about the use of additional supportive measures, such as hydration with fluids and electrolyte substitution.

For SG-related nausea or vomiting, premedication with a 2- to 3-drug combination, including dexamethasone with either a 5-hydroxytryptamine-3 receptor antagonist or a neurokinin 1 receptor antagonist, is recommended. All patients should be provided with take-home antiemetics with clear instructions for the prevention and treatment of nausea and vomiting, especially because the onset of these AEs may be delayed.

Hypersensitivity to SG usually occurs within 24 hours of dosing. Severe signs and symptoms of hypersensitivity include cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. It is important to observe patients for ≥30 minutes after each infusion and have emergency equipment available for immediate use during and after each infusion.

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A 52-year-old woman diagnosed 2 years ago with stage III triple-negative breast cancer in the left breast receives adjuvant chemotherapy. Follow-up imaging shows uptake in the right breast and metastatic lesions in the lung and liver. Tissue biopsy reveals BRCA1/2-negative metastatic breast cancer (PD-L1 CPS ≥10). She receives pembrolizumab plus chemotherapy and achieves a clinical response, and treatment is well tolerated. At a follow-up visit 11 months after starting pembrolizumab plus chemotherapy, imaging shows disease progression in the lung. She then receives sacituzumab govitecan (SG) and has been doing well with treatment. However, when she presents for cycle 6 Day 8 treatment, her absolute neutrophil count (ANC) is 850/mm3 (grade 3). She has been afebrile and feels well.

At this time, which of the following management approaches would you recommend for this patient?

Counseling Patients Receiving SG

Patients should be informed that complete hair loss may occur while receiving SG, and it is recommended that a wig prescription be offered to patients.3,18,21

Before beginning therapy with SG, patients need to be educated to appropriately recognize and report all AEs that require immediate intervention. For example, it is important that patients are aware of and able to recognize the symptoms of hypersensitivity and the gastrointestinal AEs associated with SG. Patients should be educated to call their healthcare team if and when they experience symptoms such as facial swelling, skin toxicity, breathing-related events, lightheadedness, hypotension, or the onset of fever, vomiting, and/or diarrhea so that appropriate measures can be taken to mitigate these AEs.

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