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

Author:

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

Abstract

Abstract 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.

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Oncology

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