Efficacy of trastuzumab deruxtecan in HER2-expressing solid tumors by enrollment HER2 IHC status: Post hoc analysis of DESTINY-PanTumor02 Journal Article
| Authors: | Oaknin, A.; Lee, J. Y.; Makker, V.; Oh, D. Y.; Banerjee, S.; González-Martín, A.; Jung, K. H.; Ługowska, I.; Manso, L.; Manzano, A.; Melichar, B.; Siena, S.; Stroyakovskiy, D.; Fielding, A.; Puvvada, S.; Smith, A.; Meric-Bernstam, F. |
| Article Title: | Efficacy of trastuzumab deruxtecan in HER2-expressing solid tumors by enrollment HER2 IHC status: Post hoc analysis of DESTINY-PanTumor02 |
| Abstract: | Introduction: DESTINY-PanTumor02 (NCT04482309) evaluated the efficacy and safety of trastuzumab deruxtecan (T-DXd) in pretreated patients with human epidermal growth factor receptor 2 (HER2)-expressing [immunohistochemistry (IHC) 3+/2+] solid tumors across seven cohorts: endometrial, cervical, ovarian, bladder, biliary tract, pancreatic, and other. Subgroup analyses by HER2 status were previously reported by central HER2 IHC testing, determined at enrollment or confirmed retrospectively. Reflecting the testing methods available in clinical practice, most patients (n = 202; 75.7%) were enrolled based on local HER2 IHC testing. Here, we report outcomes by HER2 IHC status as determined by the local or central test results used for study enrollment. Methods: This phase 2, open-label study evaluated T-DXd (5.4 mg/kg once every 3 weeks) for HER2-expressing (IHC 3+/2+ by local or central testing) locally advanced or metastatic disease after ≥ 1 systemic treatment or without alternative treatments. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included safety, duration of response (DOR), progression-free survival (PFS), and overall survival. Results: In total, 111 (41.6%) and 151 (56.6%) patients were enrolled with IHC 3+ and IHC 2+ tumors, respectively. In patients with IHC 3+ tumors, investigator-assessed confirmed ORR was 51.4% [95% confidence interval (CI) 41.7, 61.0], and median DOR was 14.2 months (95% CI 10.3, 23.6). In patients with IHC 2+ tumors, investigator-assessed ORR was 26.5% (95% CI 19.6, 34.3), and median DOR was 9.8 months (95% CI 4.5, 12.6). Safety was consistent with the known profile of T-DXd. Conclusion: In line with previously reported results, T-DXd demonstrated clinically meaningful benefit in patients with HER2-expressing tumors, with the greatest benefit in patients with IHC 3+ tumors. These data support the antitumor activity of T-DXd in HER2-expressing solid tumors, irrespective of whether patients are identified by local or central HER2 IHC testing. © The Author(s) 2024. |
| Keywords: | immunohistochemistry; adult; cancer chemotherapy; cancer survival; protein expression; aged; aged, 80 and over; middle aged; major clinical study; overall survival; clinical feature; clinical trial; fatigue; advanced cancer; diarrhea; drug efficacy; drug safety; solid tumor; systemic therapy; pancreas cancer; antineoplastic agent; endometrium cancer; clinical practice; neoplasm; neoplasms; metabolism; metastasis; progression free survival; ovary cancer; phase 2 clinical trial; anemia; nausea; vomiting; epidermal growth factor receptor 2; camptothecin; cohort analysis; antineoplastic activity; retrospective study; bladder cancer; pneumonia; multicenter study; uterine cervix cancer; open study; receptor, erbb-2; interstitial lung disease; drug therapy; trastuzumab; adverse drug reaction; pertuzumab; erbb2 protein, human; antibody conjugate; immunoconjugates; demographics; trastuzumab emtansine; hepatobiliary system cancer; response evaluation criteria in solid tumors; very elderly; humans; human; male; female; article; her2 testing; ecog performance status; immunological antineoplastic agent; antineoplastic agents, immunological; trastuzumab deruxtecan; tucatinib; her2-expressing; zanidatamab; trastuzumab duocarmazine; advanced/metastatic solid tumors |
| Journal Title: | Advances in Therapy |
| Volume: | 41 |
| Issue: | 11 |
| ISSN: | 0741-238X |
| Publisher: | Springer |
| Date Published: | 2024-11-01 |
| Start Page: | 4125 |
| End Page: | 4139 |
| Language: | English |
| DOI: | 10.1007/s12325-024-02975-x |
| PUBMED: | 39261417 |
| PROVIDER: | scopus |
| PMCID: | PMC11480158 |
| DOI/URL: | |
| Notes: | Source: Scopus |
