Scientific publications

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

Jun 7, 2023 | Magazine: Nature Communications

Takayuki Yoshino  1 , Maria Di Bartolomeo  2 , Kanwal Raghav  3 , Toshiki Masuishi  4 , Fotios Loupakis  5 , Hisato Kawakami  6 , Kensei Yamaguchi  7 , Tomohiro Nishina  8 , Zev Wainberg  9 , Elena Elez  10 , Javier Rodriguez  11 , Marwan Fakih  12 , Fortunato Ciardiello  13 , Kapil Saxena  14 , Kojiro Kobayashi  14 , Emarjola Bako  14 , Yasuyuki Okuda  15 , Gerold Meinhardt  14 , Axel Grothey  16 , Salvatore Siena  17   18 ; DESTINY-CRC01 investigators


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.

CITATION  Nat Commun. 2023 Jun 7;14(1):3332. doi: 10.1038/s41467-023-38032-4

Our authors

Navarre headquarters
Madrid headquarters