Current late-line treatment options for patients with advanced biliary tract cancer (BTC) provide minimal long-term advantages. In the phase 2 DESTINY-PanTumor02 (DP-02) trial, trastuzumab deruxtecan (T-DXd) demonstrated a clinically meaningful objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) in HER2-expressing solid tumors.1 T-DXd received accelerated approval in the United States in April 2024 for the treatment of unresectable or metastatic HER2-positive (IHC 3+) solid tumors in adult patients who have exhausted other treatment options.1 DESTINY-PanTumor02 included a subgroup analysis of the BTC cohort to characterize patients with an objective response, which was presented at ASCO 2024.
DESTINY-PanTumor02 is a phase 2, open-label, multicenter study (NCT04482309) that assessed T-DXd (5.4 mg/kg every 3 weeks) in patients with HER2-expressing (IHC 3+/2+ by local or central testing) locally advanced/metastatic disease2 following at least 1 systemic treatment, or in the absence of treatment options.1 The main objective of DESTINY-PanTumor02 was to determine the confirmed ORR by the investigator. Secondary objectives comprised of duration of response (DOR), disease control rate (DCR), PFS, OS, and safety measures. Exploratory objectives involved evaluating efficacy outcomes based on HER2 expression and other biomarkers to characterize patients with an objective response.1
At the data cutoff in June 2023, T-DXd had been administered to 41 patients with BTC. The median follow-up duration was 6.01 months with 2 (4.9%) patients ongoing T-DXd treatment at data cutoff. Seven (17.1%) patients had received prior anti-HER2 treatment, and 8 (19.5%) patients had previously received topoisomerase 1 inhibitor treatment. In patients with BTC and IHC 3+ expression, 9 (22.0%) patients had confirmed objective response by the investigator. Among the patients who achieved an objective response by the investigator, all 9 had a central HER2 status of IHC 3+. In all patients evaluated by the investigator, the median DOR was 8.6 months (95% confidence interval [CI], 2.1-not evaluable), the median PFS was 4.6 months (95% CI, 3.1-6.0), the median OS was 7.0 (95% CI, 4.6-10.2), and the DCR at 12 weeks was 65.9% (95% CI, 49.4-79.9). A total of 39% of patients with BTC experienced grade ≥3 drug-related adverse events.1 The most common (>5%) grade ≥3 drug-related adverse events were neutropenia (9.8%), decreased neutrophil count (9.8%), nausea (7.3%), and fatigue (7.3%). Adjudicated drug-related interstitial lung disease/pneumonitis was observed in 7 of 41 (17.1%) cases, with 5 cases classified as grade 2, 1 case as grade 3, and 1 case as grade 5.1
In patients with BTC, T-DXd exhibited meaningful clinical advantages in pretreated patients with HER2-expressing biliary tract tumors. The safety profile was consistent with the established data. These results support T-DXd as a potential treatment option for patients with HER2-expressing BTC.
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