Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer

Abstract

Colorectal cancer; Metastasis; Targeted therapies

Cáncer colorrectal; Metástasis; Terapias dirigidas

Càncer de colorectal; Metàstasi; Teràpies dirigides

DESTINY-CRC01 (NCT03384940) was a multicenter, open-label, phase 2 trial assessing the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with HER2-expressing metastatic colorectal cancer (mCRC) that progressed after ≥2 prior regimens; results of the primary analysis are published. Patients received T-DXd 6.4 mg/kg every 3 weeks and were assigned to either: cohort A (HER2-positive, immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+), cohort B (IHC 2+/ISH−), or cohort C (IHC 1+). Primary endpoint was objective response rate (ORR) by independent central review in cohort A. Secondary endpoints included ORR (cohorts B and C), duration of response, disease control rate, progression-free survival, overall survival, pharmacokinetics, and safety of T-DXd. 86 patients were enrolled (53 in cohort A, 15 in cohort B, and 18 in cohort C). Results of the primary analysis are published, reporting an ORR of 45.3% in cohort A. Here, we report the final results. No responses occurred in cohorts B or C. Median progression-free survival, overall survival, and duration of response were 6.9, 15.5, and 7.0 months, respectively. Overall serum exposure (cycle 1) of T-DXd, total anti-HER2 antibody, and DXd were similar regardless of HER2 status. Most common grade ≥3 treatment-emergent adverse events were decreased neutrophil count and anemia. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 8 patients (9.3%). These findings support the continued exploration of T-DXd in HER2-positive mCRC.

This study was sponsored by Daiichi Sankyo and funded by both Daiichi Sankyo and AstraZeneca. The sponsor was involved in data collection, analysis, interpretation, and preparation of the manuscript. We thank the patients who participated in this study, as well as their families and caregivers. We also thank the staff and investigators at all the study sites. We thank Masato Fukae, PhD, and Emi Kamiyama, PhD, for the analysis of the pharmacokinetic parameters, both of whom are employed by Daiichi Sankyo. Under the guidance of the authors, assistance in medical writing and editorial support was provided by Cindy M. Rigby, PhD, and Marianna B. Johnson, PhD, of ApotheCom, and was funded by Daiichi Sankyo.