Kadcyla (ado-trastuzumab emtansine)

P=N/A, N=20, Completed, Zhejiang Cancer Hospital; Zhejiang Cancer Hospital

P2, N=56, Recruiting, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Trastuzumab first established HER2-targeted therapy in gastric cancer, but the failure of trastuzumab emtansine (T-DM1) led to a decade-long stagnation until the advent of trastuzumab deruxtecan (T-DXd), which demonstrated robust clinical activity and defined a new standard of care. While bevacizumab failed to improve survival, the anti-VEGFR2 antibody ramucirumab emerged as an effective second-line therapy. Immune checkpoint inhibitors, including nivolumab and pembrolizumab, have been incorporated into first-line treatment for PD-L1-positive disease based on landmark trials such as CheckMate 649 and KEYNOTE-811. More recently, the CLDN18.2-targeted antibody zolbetuximab has expanded therapeutic options for biomarker-selected patients. Concurrently, a diverse pipeline of immune-based strategies-such as TROP2-directed ADCs, bispecific antibodies, and CAR-T cell therapies-is undergoing active clinical development. Together, advances in biomarker-driven antibody therapeutics are accelerating personalized cancer care and improving clinical outcomes in patients with gastric cancer.

The study was developed at the Cancer Institute of the State of São Paulo (ICESP) according to the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) recommendations.ResultsIt was possible to obtain a ranking of the 8 alternatives: the first, second and third position were respectively: neoadjuvant treatment without anthracycline and anti-HER2 therapy with only trastuzumab followed by adjuvant trastuzumab (global value 0.739); neoadjuvant treatment with anthracycline and anti-HER2 trastuzumab alone followed by adjuvant trastuzumab (global value 0.717) and neoadjuvant treament with anthracycline plus trastuzumab alone or double anti-HER2 blockade with trastuzumab and pertuzumab, followed by adjuvant T-DM1 (global value 0.697). The criteria that received the greatest weight from stakeholders were in descending order: disease-free survival, cost, severity of the disease, adverse reactions and overall survival.ConclusionMCDA made it possible to compare treatment alternatives for non-metastatic, HER2+, HR + breast cancer, with the most innovative technology T-DM1 appearing fourth.

Overall, the probability of G2P+ in patients receiving radiotherapy for HER2+ or TN BC is low. However, concurrent T-DM1 and radiotherapy was associated with significantly higher rates of pneumonitis than previously reported, suggesting a cautionary approach when combining the two therapies.

P2, N=140, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed

ctDNA-positive status after NAT can be switched to ctDNA-negative status in patients treated with T-DM1. Patients who were ctDNA-positive and treated with T-DM1 had a similar RFS to those who were ctDNA-negative, indicating that "ctDNA positivity" could be a marker determining adjuvant T-DM1 therapy.

Early-stage breast cancer is primarily managed with surgery, combined with chemotherapy, radiotherapy, endocrine therapy, and targeted therapies (such as trastuzumab and pertuzumab), significantly improving cure rates...Agents such as T-DM1 and T-DXd have significantly prolonged progression-free survival and overall survival in HER2-positive patients, providing critical treatment options for advanced-stage patients, markedly improving survival outcomes, and are now being explored in earlier lines of therapy, reshaping the treatment landscape of breast cancer...Based on the latest research advances in ADC therapy for breast cancer and incorporating clinical experience from both domestic and international settings, the Professional Committee on Anticancer Drug Clinical Research of the China Anti-Cancer Association has jointly developed the "Guidelines for managing adverse reactions to antibody-drug conjugates in breast cancer (2025 edition)". This guideline aims to provide healthcare professionals with practical guidance on the early identification, regular assessment, timely management, and follow-up monitoring of ADC-related adverse reactions or events.

Important clinical successes include the results of NOX-A12 drug and data on combined drugs based on trastuzumab in patients with metastatic breast cancer. Furthermore, very high control of breast cancer brain metastases in HER-2 positive cases was demonstrated for trastuzumab-emtansine and trastuzumab-deruxtecan. The last finding indicates the perspective for aptamer targeting glioblastoma tumor cells in conjugation with emtansine or deruxtecan.

Although T-DXd improves clinical outcomes, its adoption as a second-line treatment in Oman poses a substantial financial burden, necessitating careful budget planning to ensure long-term affordability.

Dual HER2 blockade with pertuzumab and trastuzumab demonstrated superior short- and long-term efficacy compared with trastuzumab alone, with each treatment showing a distinct but manageable safety profile.