Introduction Trastuzumab deruxtecan (T-DXd) has demonstrated significant survival benefit for patients with HER2-expressing breast and gastric cancers. In DESTINY-PanTumor02, T-DXd demonstrated clinically meaningful response rates, progression-free survival (PFS), and overall survival (OS) in HER2-expressing tumors.

Methods This open-label, Phase 2 study (NCT04482309) evaluated T-DXd (5.4 mg/kg Q3W) in patients across seven cohorts with HER2-expressing (immunohistochemistry [IHC] 3+/2+ by local [with retrospective central testing] or central testing) locally advanced/metastatic disease after ≥1 systemic treatment, or without alternative treatment. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response, PFS, OS, and safety. Exploratory endpoints included pharmacodynamic biomarkers.

Results At data cutoff (June 2023), 120 patients in the endometrial, cervical, and ovarian cancer cohorts had received treatment (median follow-up [range]: 19.94 [0.8–31.1], 12.60 [0.9–31.0], and 13.13 [0.7–30.6] months, respectively). Overall, 80.8% received ≥2 prior lines of therapy. Table 1 shows efficacy outcomes by HER2 expression levels by cohort. Table 2 shows ORR by HER2 in situ hybridization (ISH) amplification and plasma HER2 amplification by cohort. Grade (G)≥3 drug-related adverse events occurred in 54/120 (45.0%) patients; adjudicated treatment-related interstitial lung disease/pneumonitis occurred in 13/120 (10.8%) patients (n=12 G≤2; n=1 G5).

Conclusion/Implications T-DXd demonstrated clinically meaningful benefit, including responses across HER2 expression levels and in ISH+ or plasma ERBB2 amplified subgroups, and encouraging survival outcomes in patients with gynecological tumors. Safety was consistent with the known profile. These data support T-DXd as a potential treatment for patients with gynecological HER2-expressing tumors who progressed on prior therapy.