In a phase II trial (S1613) reported in the Journal of Clinical Oncology, Raghav et al found no difference in progression-free survival overall with trastuzumab/pertuzumab vs cetuximab/irinotecan in the second- or third-line treatment of RAS/BRAF wild-type HER2-positive metastatic colorectal cancer. Benefit of trastuzumab/pertuzumab was observed among patients with higher HER2 gene copy number.
Study Details
In the U.S. multicenter trial, 54 patients were randomly assigned between October 2017 and March 2022 to receive trastuzumab/pertuzumab (n = 26; trastuzumab at 6 mg/kg and pertuzumab at 420 mg once every 3 weeks) or cetuximab/irinotecan (n = 28; cetuximab at 500 mg/m2 and irinotecan at 180 mg/m2 once every 2 weeks) until progression or unacceptable toxicity. The primary endpoint was progression-free survival.
Key Findings
Among all patients, median progression-free survival was 4.7 months (95% confidence interval [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).
Among patients with HER2 gene copy number ≥ 20, median progression-free survival was 9.9 months in the trastuzumab/pertuzumab group vs 2.9 months in the cetuximab/irinotecan group; among those with HER2 gene copy number < 20, median progression-free survival was 3.0 vs 4.2 months (P interaction = .003).
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. Adverse events in the trastuzumab/pertuzumab group consisted of maculopapular rash, abdominal pain, increased alkaline phosphatase, increased alanine aminotransferase, atrial fibrillation, dyspnea, infusion-related reaction, decreased lymphocytes, and vomiting in one patient each (4%). The most common adverse events in the cetuximab/irinotecan group were acneiform rash (12%) and maculopapular rash, diarrhea, fatigue, and other gastrointestinal disorders (8% each).
The investigators concluded: “[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]. Higher levels of HER2 amplification were associated with greater degree of clinical benefit from [trastuzumab/pertuzumab] vis-à-vis [cetuximab/irinotecan].”
Kanwal Pratap Singh Raghav, MD, MBBS, of MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by National Cancer Institute grants and by Genentech Inc (a member of the Roche Group). For full disclosures of the study authors, visit ascopubs.org.
