This subgroup analysis of DESTINY-PanTumor02 Part 1 (phase II, open-label, multicenter) evaluated T-DXd 5.4 mg/kg every 3 weeks in 41 patients with locally advanced/metastatic HER2-expressing biliary tract cancer (BTC) and 25 with pancreatic cancer (PC) who had progressed after ≥1 prior systemic therapy; median follow-up was ~6 months (BTC) and ~5 months (PC).
In the BTC cohort, investigator-assessed ORR was 22.0% (95% CI 10.6%–37.6%), rising to 56.3% (95% CI 29.9%–80.2%) in centrally confirmed HER2 IHC 3+ tumors; median OS was 7.0 months. In the PC cohort, ORR was only 4.0% by investigator assessment (12.0% by ICR); median OS was 5.0 months. Drug-related ILD/pneumonitis occurred in 17.1% of BTC patients (including one grade 5 death) and 4.0% of PC patients.
- PC cohort was closed early per a prespecified futility rule (n=25 only), and very few PC patients had IHC 3+ tumors centrally (8%), severely limiting interpretation. - Moderate discordance between local and central HER2 IHC results (e.g., only 25% agreement for IHC 3+ in PC) introduces misclassification risk. - Exploratory biomarker analyses (KRAS, PD-L1) are underpowered and based on ctDNA rather than validated tumor-tissue assays.
T-DXd produces meaningful responses in pretreated HER2 IHC 3+ BTC (ORR ~56%) and is an appropriate treatment option for this group; however, accurate central HER2 testing is critical, as local IHC results frequently disagree. Monitor all patients closely for ILD/pneumonitis—rates reached 17% in BTC, with one fatal case.
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