Survival of patients with deficient mismatch repair metastatic colorectal cancer in the pre-immunotherapy era

G Emerens Wensink, Marloes A G Elferink, Anne M May, Linda Mol, Patricia A H Hamers, Sandra D Bakker, Geert-Jan Creemers, Jan Willem B de Groot, Gerty J de Klerk, Brigitte C M Haberkorn, Annebeth W Haringhuizen, Ronald Hoekstra, J Cornelis B Hunting, Emile D Kerver, Danielle Mathijssen-van Stein, Marco B Polée, Johannes F M Pruijt, Patricia Quarles van Ufford-Mannesse, Sandra Radema, Ronald C RietbroekLieke H J Simkens, Bea C Tanis, Daan Ten Bokkel Huinink, Manuel L R Tjin-A-Ton, Cathrien S Tromp-van Driel, Monique M Troost, Agnes J van de Wouw, Franchette W P J van den Berkmortel, Anke J M van der Pas, Ankie M T van der Velden, Marjan A van Dijk, Joyce M van Dodewaard-de Jong, Edith B van Druten, Theo van Voorthuizen, Gerrit Jan Veldhuis, Henk M W Verheul, Hanneke J H M J Vestjens, Jeroen Vincent, Onno W Kranenburg, Cornelis J A Punt, Geraldine R Vink, Jeanine M L Roodhart, Miriam Koopman

Research output: Contribution to journalArticleAcademicpeer-review


BACKGROUND: Metastatic colorectal cancer patients with deficient mismatch repair (dMMR mCRC) benefit from immunotherapy. Interpretation of the single-arm immunotherapy trials is complicated by insignificant survival data during systemic non-immunotherapy. We present survival data on a large, comprehensive cohort of dMMR mCRC patients, treated with or without systemic non-immunotherapy.

METHODS: Two hundred and eighty-one dMMR mCRC patients (n = 54 from three prospective Phase 3 CAIRO trials; n = 227 from the Netherlands Cancer Registry). Overall survival was analysed from diagnosis of mCRC (OS), from initiation of first-line (OS1) and second-line (OS2) systemic treatment. Cox regression analysis examined prognostic factors. As comparison for OS 2746 MMR proficient mCRC patients were identified.

RESULTS: Of 281 dMMR patients, 62% received first-line and 26% second-line treatment. Median OS was 16.0 months (13.8-19.6) with antitumour therapy and 2.5 months (1.8-3.5) in untreated patients. OS1 was 12.8 months (10.7-15.2) and OS2 6.2 months (5.4-8.9) in treated dMMR patients. Treated dMMR patients had a 7.6-month shorter median OS than pMMR patients.

CONCLUSION: Available data from immunotherapy trials lack a control arm with standard systemic treatment. Given the poor outcome compared to the immunotherapy results, our data strongly suggest a survival benefit of immunotherapy in dMMR mCRC patients.

Original languageEnglish
Pages (from-to)399-406
Number of pages8
JournalBritish Journal of Cancer
Issue number2
Early online date13 Oct 2020
Publication statusPublished - Jan 2021


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