Trastuzumab emtansine

Grace Liu from Sino Biological discusses Antibody-Drug Conjugates (ADCs), a cancer therapy combining precision targeting with potent cytotoxic drugs. ADCs consist of a monoclonal antibody, cytotoxic payload, and linker, balancing efficacy and safety. Sino Biological offers comprehensive ADC development solutions, aiding in the complex process from discovery to clinical studies.

The 2024 NCCN Breast Cancer guidelines update includes ribociclib plus an aromatase inhibitor as a preferred regimen for HR-positive, HER2-negative early breast cancer. Ribociclib is the only category 1 CDK4/6 inhibitor for first-line treatment in combination with an AI. The guidelines also add adjuvant ribociclib for premenopausal patients with HR-positive, HER2-negative disease, and revise other treatment pathways. The FDA approval of adjuvant ribociclib may apply to a wider population than abemaciclib, with ribociclib given at 400 mg for 3 years, compared to abemaciclib's 2 years.

HER2-targeted therapy is standard for stage II/III HER2-positive breast cancer, with options like trastuzumab and pertuzumab delivered IV or subcutaneously. Clinical trials explore de-escalation or escalation of therapy based on patient and disease characteristics, with pivotal studies like NeoSphere, TRYPHAENA, FeDeriCa, PHranceSCa, and KATHERINE informing treatment paradigms. T-DM1 is standard for residual disease post-neoadjuvant therapy.

BCRF highlights recent research advancements in treating HER2-positive metastatic breast cancer, particularly brain metastases, with drugs like tucatinib and trastuzumab deruxtecan, emphasizing the need for continued research to improve patient outcomes.

Experts at the IASLC World Conference on Lung Cancer discussed HER2-directed treatments, highlighting recent approvals and clinical trial updates. They emphasized the importance of biomarker testing and safety profiles of HER2-targeted agents across cancer types. The panel debated the use of T-DXd in different lines of therapy for HER2-mutated non-small cell lung cancer (NSCLC) and the potential of TKIs like zongertinib and BAY 2927088. They also explored the implications of HER2 expression in tumor-agnostic trials and the role of AI in predicting patient responses.

The phase III TULIP trial found trastuzumab duocarmazine (T-Duo) improved progression-free survival vs physician's choice in HER2-positive advanced breast cancer, though associated with ocular toxicity leading to higher discontinuation rates.

Advances in precision medicine have transformed NSCLC treatment, with broad molecular testing now recommended. HER2 mutation, present in 3% of NSCLC patients, is associated with aggressive disease and brain metastases. No first-line HER2-targeted therapies are approved; current options include immunotherapy and platinum doublet. Zongertinib and BAY 2927088, oral HER2-targeted TKIs, show promise in pre-treated patients, with zongertinib demonstrating a 66.7% ORR and BAY 2927088 showing a 72.1% ORR. Both agents have been granted breakthrough therapy designation by the FDA.

NSCLC with HER2 mutations, found in 3% of advanced non-squamous cases, is associated with poor prognosis and higher incidence of brain metastases. Standard first-line chemotherapy has limited efficacy, and HER2-targeted agents lag in NSCLC treatment. Recent studies using HER2 TKIs, ADCs, and monoclonal antibodies show promising results, with Trastuzumab deruxtecan (T-DXd) achieving 55% ORR and 8.2 months mPFS in DESTINY-Lung01 trial. Zongertinib, a novel HER2-specific TKI, demonstrated 62% ORR and 97% DCR in HER2 mutation-positive NSCLC patients, with low toxicity rates, suggesting a potential better tolerated treatment option.

Targeted treatment based on mutational status showed higher overall response rate (ORR) and progression-free survival (PFS) vs standard of care (SOC) in pretreated metastatic solid tumors, according to the phase 2 ROME trial. ORR was 17.0% in the targeted treatment arm vs 9.5% in the SOC arm (P = .026). Median PFS was 3.7 months in the targeted arm vs 2.8 months in the SOC arm (HR 0.64; 95% CI, 0.51-0.80; P < .001).