Tislelizumab plus lenvatinib in unresectable locally advanced biliary tract cancer

Dear Editor, We read with interest the report of the ZSAB-TransGOLP study evaluating tislelizumab, lenvatinib, and GEMOX as conversion therapy in unresectable locally advanced biliary tract cancer (BTC).[1] The authors are to be commended for conducting a prospective multicenter trial in a challenging disease setting and for reporting an impressive R0 resection rate of 63%. Nevertheless, we wish to highlight several points. The efficacy outcomes appear promising, they remain preliminary. The median follow-up of 19.5 months is relatively short to establish durable overall survival benefit, and it is unclear whether the higher R0 rate will translate into long-term survival improvements. In contrast, pivotal trials such as ABC-02 (gemcitabine–cisplatin)[2] and TOPAZ-1 (gemcitabine–cisplatin–durvalumab)[3] provide systemic benchmarks with mature data. Reports of FOLFIRINOX[4] have also demonstrated conversion in selected patients. A randomized comparison would therefore be essential to confirm superiority. Second, the regimen’s safety profile is concerning. Grade 3–4 neutropenia was observed in 34% of patients, and nearly half experienced severe toxicities. Although no treatment-related deaths occurred, this toxicity burden appears greater than that reported with gemcitabine–cisplatin or gemcitabine–cisplatin–durvalumab. Importantly, quality-of-life outcomes were not presented, a key omission in this context. The single-arm, phase II design inherently limits interpretability. All enrolled patients were of origin from China, restricting generalizability to multiethnic populations. Moreover, the determination of resectability at only two centers raises the possibility of selection bias. Finally, the rationale for including lenvatinib is extrapolated largely from hepatocellular carcinoma data; its role in BTC remains unestablished. Clarification on why lenvatinib was chosen over other TKIs would be valuable. In summary, while ZSAB-TransGOLP provides an intriguing signal for conversion therapy in BTC, these results should be regarded as hypothesis-generating rather than practice-changing, pending validation in randomized phase III studies with diverse populations and longer follow-up. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.