Dataset Information

Case Report: MAP2K1 K57N mutation is associated with primary resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer.

ABSTRACT:

Background

We aim to identify the prevalence and the role of the MAP2K1 K57N mutation in predicting resistance to anti-EGFR agents in metastatic colorectal cancer (mCRC) patients.

Methods

We retrospectively reviewed tumor-based next generation sequencing (NGS) results from mCRC patients screened for enrollment in the GO40872/STARTRK-2 clinical trial between July 2019 and March 2021. Then, in patients harboring microsatellite stable (MSS) RAS and BRAF wild-type MAP2K1 mutant mCRC, we reviewed outcome to treatment with anti-EGFR monoclonal antibodies.

Results

A total of 246 mCRC patients were screened. Most of them, 215/220 (97.7%), were diagnosed with MSS mCRC and 112/215 (52.1%) with MSS, RAS and BRAF wild-type mCRC. Among the latter, 2/112 (1.8%) had MAP2K1 K57N mutant mCRC and both received anti-EGFR monotherapy as third line treatment. In both patients, MAP2K1 K57N mutant tumors proved primary resistant to anti-EGFR agent panitumumab monotherapy. Of interest, one of these patients was treated with anti-EGFR agents three times throughout his course of treatment, achieving some clinical benefit only when associated with other cytotoxic agents (FOLFOX or irinotecan).

Conclusion

We verified in a clinical real-world setting that MAP2K1 K57N mutation is a resistance mechanism to anti-EGFR agents in mCRC. Thus, we suggest avoiding the administration of these drugs to MSS RAS and BRAF wild-type MAP2K1 N57K mutant mCRC.

SUBMITTER: Mauri G

PROVIDER: S-EPMC9676472 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Case Report: <i>MAP2K1 K57N</i> mutation is associated with primary resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer.

Mauri Gianluca G Patelli Giorgio G Gori Viviana V Lauricella Calogero C Mussolin Benedetta B Amatu Alessio A Bencardino Katia K Tosi Federica F Bonazzina Erica E Bonoldi Emanuela E Bardelli Alberto A Siena Salvatore S Sartore-Bianchi Andrea A

Frontiers in oncology 20221107

<h4>Background</h4>We aim to identify the prevalence and the role of the <i>MAP2K1 K57N</i> mutation in predicting resistance to anti-EGFR agents in metastatic colorectal cancer (mCRC) patients.<h4>Methods</h4>We retrospectively reviewed tumor-based next generation sequencing (NGS) results from mCRC patients screened for enrollment in the GO40872/STARTRK-2 clinical trial between July 2019 and March 2021. Then, in patients harboring microsatellite stable (MSS) <i>RAS</i> and <i>BRAF</i> wild-type ...[more]

PMID: 36419886

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