Dr Ostwal on T-DM1 in Pretreated HER2+ Advanced Biliary Tract Cancer

Vikas S. Ostwal, MD, Tata Memorial Centre, discusses findings from the single-arm, phase 2 TAB-3 trial (CTRI/2023/07/055785) evaluating ado-trastuzumab emtansine (T-DM1; Kadcyla) as second-line therapy in patients with HER2-positive advanced biliary tract cancer.

In this investigator-initiated study, Ostwal notes that the safety and efficacy of T-DM1 was evaluated in patients with HER2-positive disease (immunohistochemistry [IHC] 3+ or IHC 2+/FISH-positive) advanced biliary tract cancer who had previously received systemic chemotherapy, including gemcitabine plus cisplatin or the gemcitabine plus cisplatin and nab-paclitaxel (Abraxane). Patients received T-DM1 at 3.6 mg/kg every 3 weeks until disease progression, unacceptable toxicity, or patient withdrawal.

The primary end point was progression-free survival (PFS), and secondary end points included overall response rate (ORR), disease control rate (DCR), overall survival (OS), and the incidence of grade 3 and 4 treatment-related adverse effects (TRAEs).

Results presented at the 2025 Gastrointestinal Cancers Symposium demonstrated that at a median follow-up of 7.1 months (95% CI, 5.1-9.1), the 3-month PFS rate was 51.2% (95% CI, 33.4%-69.0%), and the median PFS was 3.1 months (95% CI, 2.3-3.8) in evaluable patients (n = 40). The study did not meet its PFS primary end point compared with historical control outcomes.

The median OS was 7.1 months (95% CI, 5.1-9.1). The ORR was 12.5%, including partial responses in 5 patients. Additionally, 8 patients (20%) achieved stable disease, yielding a DCR of 32.5%.

Ostwal notes that the safety profile of T-DM1 was manageable. Grade 3 or 4 TRAEs occurred in 28% of patients, with the most common being grade 2 fatigue (n = 6) and grade 3 thrombocytopenia (n = 2). Most patients tolerated therapy well, with no unexpected toxicities.

Ostwal concludes that although T-DM1 was well tolerated, the lack of PFS benefit emphasizes the need for further research to refine patient selection and optimize treatment strategies for HER2-positive biliary tract cancer.