Highlights
- •RAS gene status could be changed before and after the chemotherapy.
- •mCRC patients with NeoRAS wild-type could gain the benefit from EGFR inhibitor.
- •Retesting of RAS genes contributes to optimise treatment strategy of EGFR inhibitor.
Abstract
Upfront KRAS and NRAS gene testing (‘RAS’) is the standard of care for metastatic colorectal cancer (mCRC), to guide first-line
treatment. The presence of RAS mutation (MT) is a negative predictor for the efficacy of anti-EGFR antibodies and
the use of cetuximab and panitumumab is restricted to RAS wild-type (WT) mCRC. Conversion from RAS WT to RAS MT mCRC after treatment with anti-EGFR antibodies is a known and well-described acquired
resistance mechanism. The by far less frequent ‘NeoRAS wild-type’ phenomenon (reversion from RAS MT to RAS WT) has recently drawn attention. The proposed effect of chemotherapy on RAS status in mCRC patients is not fully understood. Because of the intriguing biological
consequence of a RAS MT to RAS WT reversion, subsequent treatment of NeoRAS WT patients with anti-EGFR antibodies is increasingly being discussed. Here, we report
three clinical cases of NeoRAS WT mCRC patients, which received standard-of-care regimens for RAS MT mCRC. Anti-EGFR antibodies were used in two out of three patients after progression
of the disease. One of the patients had a long-term response. In line with our observations,
NeoRAS WT phenomenon occurs in clinical practice. Retesting of RAS status during treatment should be discussed in patients with unusual long-term clinical
courses of RAS MT mCRC to optimise treatment strategy and to evaluate the use of anti-EGFR antibodies.
Keywords
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Article info
Publication history
Published online: June 18, 2021
Accepted:
May 7,
2021
Received in revised form:
April 30,
2021
Received:
March 9,
2021
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
