Efficacy of anti-epidermal growth factor antibody rechallenge in RAS/BRAF wild-type metastatic colorectal cancer: a multi-institutional observational study

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2024年7月27日

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Koshiro Fukuda,
Hiroki Osumi,
Yuri Yoshinami,
Akira Ooki,
Atsuo Takashima,
Takeru Wakatsuki,
Hidekazu Hirano,
Izuma Nakayama,
Kota Ouchi,
Ryoichi Sawada,
Shota Fukuoka,
Mariko Ogura,
Daisuke Takahari,
Keisho Chin,
Hirokazu Shoji,
Natsuko Okita,
Ken Kato,
Naoki Ishizuka,
Narikazu Boku,
Kensei Yamaguchi,
Eiji Shinozaki

摘要

Purpose

To investigate circulating tumor DNA (ctDNA) RAS mutant (MT) incidence before salvage-line treatment and the clinicopathological features and molecular biological factors associated with the efficacy of anti-epithelial growth factor receptor (EGFR) monoclonal antibody (mAb) rechallenge for tissue RAS/BRAF wild type (WT) metastatic colorectal cancer (mCRC).

Methods

This multi-institutional retrospective observational study included 74 patients with mCRC with tissue RAS/BRAF WT refractory to first-line chemotherapy containing anti-EGFR mAb. ctDNA RAS status was assessed using the OncoBEAM™ RAS CRC Kit. We explored the clinicopathological features associated with ctDNA RAS status and the factors related to anti-EGFR mAb rechallenge efficacy in multivariate Cox proportional hazard regression.

Results

The incidence of RAS MT in ctDNA was 40.5% (30/74), which was associated with primary tumor resection (P = 0.016), liver metastasis (P < 0.001), and high tumor marker levels (P < 0.001). Among the 39 patients treated with anti-EGFR mAb rechallenge, those with ctDNA RAS WT showed significantly longer progression-free survival (PFS) than those with ctDNA RAS MT (median 4.1 vs. 2.7 months, hazard ratio [HR] = 0.39, P = 0.045). Patients who responded to first-line anti-EGFR mAb showed significantly longer PFS (HR = 0.21, P = 0.0026) and overall survival (OS) (HR = 0.23, P = 0.026) than those with stable disease.

Conclusions

The incidence of ctDNA RAS MT mCRC was 40.5%, which was associated with liver metastases and high tumor volumes. Anti-EGFR mAb rechallenge may be effective for patients with mCRC who responded to first-line chemotherapy containing anti-EGFR mAb. No patients with RAS MT in ctDNA responded to anti-EGFR mAb rechallenge.