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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

TROPION-Breast01: Safety of Dato-DXd

In the TROPION-Breast01 trial of the investigational Dato-DXd vs chemotherapy for previously treated patients with inoperable or metastatic HR-positive/HER2-negative breast cancer, the treatment-related adverse events (TRAEs) associated with Dato-DXd were predominantly grade 1/2 (73%).22 Both SG and Dato-DXd target TROP-2, but unlike SG, the most common TRAEs that led to dose interruptions for patients who received Dato-DXd were nonhematologic events including fatigue, infusion-related reactions, ILD, and stomatitis. More patients who received chemotherapy (42%) experienced neutropenia (any grade) compared with those who received Dato-DXd (11%), and only 1% of patients who received Dato-DXd experienced grade ≥3 neutropenia vs 31% of patients who received chemotherapy. Only 3% of patients who received Dato-DXd required G-CSF support for treatment-related neutropenia compared with 30% of patients who received chemotherapy.

All-grade stomatitis was reported in 50% of patients who received Dato-DXd compared with 13% of patients who received chemotherapy. Grade ≥3 stomatitis was reported in 6% of patients who received Dato-DXd compared with 3% of patients who received chemotherapy. There were no treatment-related deaths with Dato-DXd, and only 6% of patients experienced serious TRAEs with Dato-DXd vs 9% with chemotherapy.

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TULIP: Trastuzumab Duocarmazine vs Physician’s Choice of Treatment in HER2-Positive ABC: Toxicity

Trastuzumab duocarmazine is another investigational ADC. Its target is HER2, and it comprises a cytotoxic duocarmycin payload.23 Trastuzumab duocarmazine was investigated vs physician’s choice of treatment in the phase III TULIP trial for patients with HER2-positive advanced breast cancer who had received ≥2 previous HER2-directed regimens or patients with metastatic disease or disease progression during or after receiving T-DM1.24 In this trial, 96.5% of patients who received trastuzumab duocarmazine experienced ≥1 TEAE compared with 96.4% of patients who received physician’s choice of treatment. Of this, 52.4% and 48.2% of patients experienced grade ≥3 TEAEs with trastuzumab duocarmazine and physician’s choice of treatment, respectively. Ocular toxicities and fatigue were the most frequently reported TEAEs with trastuzumab duocarmazine. Ocular toxicities included conjunctivitis, keratitis, dry eye, and increased lacrimation. Of the 78.1% of patients who experienced ocular toxicity with trastuzumab duocarmazine, 21.5% discontinued treatment, and dose modification occurred in 22.9%. ILD/pneumonitis occurred with trastuzumab duocarmazine, resulting in treatment discontinuations in 5.2% of patients and dose modification in 2.1% of patients. Trastuzumab duocarmazine also was associated with gastrointestinal, dermatologic, metabolic, and hematologic AEs.

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