Trastuzumab deruxtecan in HER2-expressing gynecologic cancers from DESTINY-PanTumor02: antitumor activity, safety, and exploratory biomarker analyses

OBJECTIVE: To investigate antitumor activity, safety, and exploratory subgroup analyses for trastuzumab deruxtecan (T-DXd) in human epidermal growth factor receptor 2 (HER2)-expressing (immunohistochemistry IHC 3+ and 2+) gynecologic cancers. METHODS: DESTINY-PanTumor02 is a 2-part, open-label, multicenter, phase 2 study. Pretreated patients with locally advanced, metastatic, or unresectable HER2-expressing solid tumors received T-DXd 5.4 mg/kg. Primary endpoint was investigator-assessed (INV) confirmed objective response rate (ORR). Secondary endpoints included safety, ORR by independent central review (ICR), progression-free survival, and overall survival. Exploratory endpoints included ORRs by biomarker status. This analysis reports data from the endometrial, cervical, and ovarian cancer cohorts. RESULTS: At primary analysis data cutoff, 120 patients received treatment across 3 gynecologic cancer cohorts. Median follow-up (range) was 19.9 months (0.8-31.1), 12.6 months (0.9-31.0), and 13.1 months (0.7-30.6) in the endometrial, cervical, and ovarian cancer cohorts, respectively. INV confirmed ORRs (n/N 95% confidence interval) in the endometrial, cervical, and ovarian cancer cohorts were 57.5% (23/40 40.9-73.0), 50.0% (20/40 33.8-66.2), and 45.0% (18/40 29.3-61.5), respectively, and by ICR were 57.5% (23/40 40.9-73.0), 37.5% (15/40 22.7-54.2), and 42.5% (17/40 27.0-59.1), respectively. ORRs were highest for the HER2 IHC 3+ populations. Although patient numbers were small in some subgroups, objective responses were observed regardless of tumor histology, prior treatment, and biomarker expression/mutation status. Adjudicated interstitial lung disease/pneumonitis occurred in 13 patients (10.8%; Grade 1, n=4; Grade 2, n=8; Grade 5, n=1). CONCLUSION: T-DXd induced clinically meaningful ORRs, with safety consistent with the known profile. Data further support T-DXd as a therapeutic option for pretreated HER2-expressing gynecologic cancers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04482309.