Enhertu in HER2-Positive Metastatic Colorectal Cancer: DESTINY-CRC02 Trial

At the ASCO 2023 Annual Meeting, Dr. Kanwal Pratap Singh Raghav and colleagues from MD Anderson Cancer Center presented the results of the DESTINY-CRC02 Phase 2 clinical trial. This study investigated the efficacy and safety of Enhertu (Trastuzumab deruxtecan) in patients with HER2-positive advanced colorectal cancer (CRC).

Study Design: DESTINY-CRC02 Trial

The trial evaluated two different doses of Enhertu in patients with HER2-positive (IHC 3+ or IHC 2+/ISH positive) metastatic CRC who had progressed on prior therapies:

1. 5.4 mg/kg Group (N=82)
2. 6.4 mg/kg Group (N=40)

The primary endpoint was objective response rate (ORR) as assessed by independent central review.

Key Efficacy Results (Median Follow-up 8.9 Months)

• Objective Response Rate (ORR):
  • 5.4 mg/kg Group: 37.8%
  • 6.4 mg/kg Group: 27.5%
• Median Progression-Free Survival (PFS):
  • 5.4 mg/kg Group: 5.8 months
  • 6.4 mg/kg Group: 5.5 months
• Median Duration of Response (DOR): 5.5 months for both groups.

Safety Profile

The safety profile favored the lower dose:

• Grade 3+ Adverse Events: 49.4% (5.4 mg/kg) vs. 59.0% (6.4 mg/kg).
• Drug-Induced Interstitial Lung Disease (ILD): 8.4% (5.4 mg/kg) vs. 12.8% (6.4 mg/kg). Most ILD cases were Grade 1 or 2.

Conclusion

The researchers concluded that Enhertu demonstrates significant antitumor activity in HER2-positive metastatic CRC. Based on the risk-benefit profile, 5.4 mg/kg was identified as the optimal dose for this patient population, offering high efficacy with a more manageable safety profile compared to the 6.4 mg/kg dose.

Source: ASCO 2023 - DESTINY-CRC02 Abstract #3501

#ColorectalCancer #HER2Positive #Enhertu #TDXd #DESTINYCRC02 #CancerResearch #ADC

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