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Background <p>HER2-positive or <i>ERBB</i>2 amplified (<i>ERBB</i>2 amp+) metastatic colorectal cancer (mCRC) is an important subgroup due to emerging HER2-targeted therapies. Although <i>ERBB</i>2 amplification is associated with anti-EGFR antibody resistance, optimal first-line treatment remains unclear.</p> Methods <p>We analysed data from the Flatiron Health-Foundation Medicine CRC clinico-genomic database, including patients with stage IV or recurrent mCRC diagnosed between January 2012 and March 2022 who underwent tissue-based comprehensive genomic profiling. <i>ERBB</i>2 amp<i>+</i> was defined as an <i>ERBB</i>2 copy number ≥+3 of the tumour base ploidy.</p> Results <p>Among 5545 patients, 144 (3.1%) had <i>ERBB</i>2 amp+ mCRC. These patients showed significantly worse real-world progression-free survival (rwPFS) than <i>ERBB</i>2 amp− patients (median 7.6 vs. 8.7 months; hazard ratio [HR]: 1.20, 95% confidence interval [CI]: 1.01–1.43, p = 0.04). This trend persisted in patients with left-sided <i>RAS/BRAF</i> V600E wild-type and non-MSI-H mCRC treated with chemotherapy plus anti-EGFR antibody (median 8.7 vs. 12.5 months; HR: 2.18, p = 0.02; adjusted HR: 2.33, p = 0.046) or chemotherapy plus bevacizumab (median 8.9 vs. 10.5 months; HR: 1.65, p = 0.04; adjusted HR: 1.75, p = 0.04). Real-world overall survival did not differ significantly.</p> Conclusion <p><i>ERBB</i>2 amp+ mCRC is a small but clinically relevant subgroup with inferior rwPFS across current first-line treatments, highlighting the need for better strategies.</p>

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Survival outcomes of ERBB2-amplified metastatic colorectal cancer treated with first-line chemotherapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月8日

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  • Yuki Matsubara,
  • Hideaki Bando,
  • Yoshiaki Nakamura,
  • Toshihiro Misumi,
  • Dionne Ng,
  • Eri Tajima,
  • Harlan Pittell,
  • Atsushi Ohtsu,
  • Takayuki Yoshino

摘要

Background

HER2-positive or ERBB2 amplified (ERBB2 amp+) metastatic colorectal cancer (mCRC) is an important subgroup due to emerging HER2-targeted therapies. Although ERBB2 amplification is associated with anti-EGFR antibody resistance, optimal first-line treatment remains unclear.

Methods

We analysed data from the Flatiron Health-Foundation Medicine CRC clinico-genomic database, including patients with stage IV or recurrent mCRC diagnosed between January 2012 and March 2022 who underwent tissue-based comprehensive genomic profiling. ERBB2 amp+ was defined as an ERBB2 copy number ≥+3 of the tumour base ploidy.

Results

Among 5545 patients, 144 (3.1%) had ERBB2 amp+ mCRC. These patients showed significantly worse real-world progression-free survival (rwPFS) than ERBB2 amp− patients (median 7.6 vs. 8.7 months; hazard ratio [HR]: 1.20, 95% confidence interval [CI]: 1.01–1.43, p = 0.04). This trend persisted in patients with left-sided RAS/BRAF V600E wild-type and non-MSI-H mCRC treated with chemotherapy plus anti-EGFR antibody (median 8.7 vs. 12.5 months; HR: 2.18, p = 0.02; adjusted HR: 2.33, p = 0.046) or chemotherapy plus bevacizumab (median 8.9 vs. 10.5 months; HR: 1.65, p = 0.04; adjusted HR: 1.75, p = 0.04). Real-world overall survival did not differ significantly.

Conclusion

ERBB2 amp+ mCRC is a small but clinically relevant subgroup with inferior rwPFS across current first-line treatments, highlighting the need for better strategies.