Trastuzumab/Pertuzumab Shows Promise for HER2-Positive Metastatic Colorectal Cancer

Trastuzumab/Pertuzumab vs Cetuximab/Irinotecan in RAS/BRAF Wild-Type HER2-Positive Metastatic Colorectal Cancer

In a pivotal phase II trial (S1613) reported in the Journal of Clinical Oncology, researchers led by Kanwal Pratap Singh Raghav, MD, MBBS, of MD Anderson Cancer Center, explored the efficacy and safety of trastuzumab/pertuzumab versus cetuximab/irinotecan in the second- or third-line treatment of RAS/BRAF wild-type HER2-positive metastatic colorectal cancer. The study, conducted across multiple U.S. centers between October 2017 and March 2022, involved 54 patients randomly assigned to receive either trastuzumab/pertuzumab or cetuximab/irinotecan.

Study Details

• Participants: 54 patients with RAS/BRAF wild-type HER2-positive metastatic colorectal cancer.
• Treatment Groups: Trastuzumab/pertuzumab (n = 26) vs cetuximab/irinotecan (n = 28).
• Dosage: Trastuzumab at 6 mg/kg and pertuzumab at 420 mg once every 3 weeks; cetuximab at 500 mg/m2 and irinotecan at 180 mg/m2 once every 2 weeks.
• Primary Endpoint: Progression-free survival.

Key Findings

• Overall Progression-Free Survival: Median progression-free survival was 4.7 months (95% CI = 1.9–7.6 months) in the trastuzumab/pertuzumab group vs 3.7 months (95% CI = 1.6–6.7 months) in the cetuximab/irinotecan group (HR= 0.79, 95% CI = 0.43–1.45, P = .44).
• HER2 Gene Copy Number Impact: Patients with HER2 gene copy number ≥ 20 had a median progression-free survival of 9.9 months with trastuzumab/pertuzumab vs 2.9 months with cetuximab/irinotecan. Those with HER2 gene copy number < 20 had median progression-free survival of 3.0 vs 4.2 months (P interaction = .003).
• Adverse Events: Grade 3 treatment-related adverse events occurred in 23.1% of the trastuzumab/pertuzumab group vs 46.1% of the cetuximab/irinotecan group, with no grade 4 or 5 events reported.

Conclusion

The investigators concluded that trastuzumab/pertuzumab appears to be a safe and effective cytotoxic chemotherapy-free option for patients with RAS/BRAF wild-type, HER2-positive metastatic colorectal cancer, especially for those with higher levels of HER2 amplification. This treatment offers a promising alternative with a favorable safety profile, highlighting the importance of personalized medicine in cancer treatment strategies.