Clinical features associated with NeoRAS wild-type metastatic colorectal cancer A SCRUM-Japan GOZILA substudy

Hiroki Osumi, Eiji Shinozaki (), Yoshiaki Nakamura, Taito Esaki, Hisateru Yasui, Hiroya Taniguchi, Hironaga Satake, Yu Sunakawa, Yoshito Komatsu, Yoshinori Kagawa, Tadamichi Denda, Manabu Shiozawa, Taroh Satoh, Tomohiro Nishina, Masahiro Goto, Naoki Takahashi, Takeshi Kato, Hideaki Bando, Kensei Yamaguchi and Takayuki Yoshino ()
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Hiroki Osumi: Cancer Institute Hospital of Japanese Foundation for Cancer Research
Eiji Shinozaki: Cancer Institute Hospital of Japanese Foundation for Cancer Research
Yoshiaki Nakamura: National Cancer Center Hospital East
Taito Esaki: National Hospital Organization Kyushu Cancer Center
Hisateru Yasui: Kobe City Medical Center General Hospital
Hiroya Taniguchi: Aichi Cancer Center Hospital
Hironaga Satake: Kochi Medical School
Yu Sunakawa: St. Marianna University School of Medicine
Yoshito Komatsu: Hokkaido University Hospital
Yoshinori Kagawa: Osaka General Medical Center
Tadamichi Denda: Chiba Cancer Center
Manabu Shiozawa: Kanagawa Cancer Center
Taroh Satoh: Osaka University Hospital
Tomohiro Nishina: National Hospital Organization Shikoku Cancer Center
Masahiro Goto: Osaka Medical and Pharmaceutical University Hospital
Naoki Takahashi: Saitama Cancer Center
Takeshi Kato: National Hospital Organization Osaka National Hospital
Hideaki Bando: National Cancer Center Hospital East
Kensei Yamaguchi: Cancer Institute Hospital of Japanese Foundation for Cancer Research
Takayuki Yoshino: National Cancer Center Hospital East

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: Abstract “NeoRAS WT” refers to the loss of RAS mutations (MTs) following first-line treatment in metastatic colorectal cancer (mCRC). We evaluate the incidence and clinicopathological characteristics of NeoRAS WT mCRC using next-generation sequencing of plasma circulating tumor DNA. Patients with mCRC enrolled in the GOZILA study initially diagnosed with tissue RAS MT mCRC and received subsequent systemic therapy are eligible. NeoRAS WT is defined as the absence of detectable RAS MT in plasma and assessed in all eligible patients (Group A) and in a subgroup with at least one somatic alteration detected in plasma (Group B). Overall, 478 patients are included. NeoRAS WT prevalence is 19.0% (91/478) in Group A and 9.8% (42/429) in Group B. Absence of liver or lymph node metastasis and tissue RAS MTs other than KRAS exon 2 MTs are significantly associated with NeoRAS WT emergence. Overall, 1/6 and 2/6 patients with NeoRAS WT treated with anti-EGFR monoclonal antibodies (mAbs) show partial response and stable disease for ≥6 months, respectively. NeoRAS WT mCRC is observed at a meaningful prevalence, and anti-EGFR mAb-based therapy may be effective.

Date: 2024
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DOI: 10.1038/s41467-024-50026-4

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