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.