G Emerens Wensink1, Marloes A G Elferink2, Anne M May3, Linda Mol2, Patricia A H Hamers1, Sandra D Bakker4, Geert-Jan Creemers5, Jan Willem B de Groot6, Gerty J de Klerk7, Brigitte C M Haberkorn8, Annebeth W Haringhuizen9, Ronald Hoekstra10, J Cornelis B Hunting11, Emile D Kerver12, Danielle Mathijssen-van Stein13, Marco B Polée14, Johannes F M Pruijt15, Patricia Quarles van Ufford-Mannesse16, Sandra Radema17, Ronald C Rietbroek18, Lieke H J Simkens19, Bea C Tanis20, Daan Ten Bokkel Huinink21, Manuel L R Tjin-A-Ton22, Cathrien S Tromp-van Driel23, Monique M Troost24, Agnes J van de Wouw25, Franchette W P J van den Berkmortel26, Anke J M van der Pas27, Ankie M T van der Velden28, Marjan A van Dijk29, Joyce M van Dodewaard-de Jong30, Edith B van Druten31, Theo van Voorthuizen32, Gerrit Jan Veldhuis33, Henk M W Verheul34, Hanneke J H M J Vestjens25, Jeroen Vincent35, Onno W Kranenburg36,37, Cornelis J A Punt38, Geraldine R Vink1,2, Jeanine M L Roodhart1, Miriam Koopman39. 1. Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, 3584CG, Utrecht, The Netherlands. 2. Department of Research, Netherlands Comprehensive Cancer Organisation, Postbus 19079, 3501DB, Utrecht, The Netherlands. 3. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, P.O. Box 85500, 3508GA, Utrecht, The Netherlands. 4. Department of Medical Oncology, Zaans Medical Center, Postbus 210, 1500EE, Zaandam, The Netherlands. 5. Department of Medical Oncology, Catharina Hospital, Postbus 1350, 5602ZA, Eindhoven, The Netherlands. 6. Department of Medical Oncology, Isala Hospital, Dokter van Heesweg 2, 8025AB, Zwolle, The Netherlands. 7. Department of Medical Oncology, Spaarne Gasthuis, Spaarnepoort 1, 2134TM, Hoofddorp, The Netherlands. 8. Department of Medical Oncology, Maasstad Hospital, Postbus 9100, 3007AC, Rotterdam, The Netherlands. 9. Department of Medical Oncology, Hospital Gelderse Vallei, Willy Brandtlaan 10, 6716RP, Ede, The Netherlands. 10. Department of Medical Oncology, Ziekenhuisgroep Twente, Postbus 7600, 7600SZ, Almelo, The Netherlands. 11. Department of Medical Oncology, St. Antonius Hospital, Postbus 2500, 3430EM, Nieuwegein, The Netherlands. 12. Department of Medical Oncology, OLVG, Oosterpark 9, 1091AC, Amsterdam, The Netherlands. 13. Department of Medical Oncology, Franciscus Gasthuis & Vlietland, Vlietlandplein, 3118JH, Schiedam, The Netherlands. 14. Department of Medical Oncology, Medical Center Leeuwarden, Postbus 888, 8901BR, Leeuwarden, The Netherlands. 15. Department of Medical Oncology, Jeroen Bosch Hospital, Postbus 90153, 5200ME, 's-Hertogenbosch, The Netherlands. 16. Department of Medical Oncology, HagaZiekenhuis, Els Borst-Eilersplein 275, 2545AA, den Haag, The Netherlands. 17. Department of Medical Oncology, Radboud University Medical Center, Postbus 9101, 6500HB, Nijmegen, the Netherlands. 18. Department of Medical Oncology, Rode Kruis Hospital, Postbus 1074, 1940EB, Beverwijk, The Netherlands. 19. Department of Medical Oncology, Maxima Medical Center, Postbus 90052, 5600PD, Eindhoven, The Netherlands. 20. Department of Medical Oncology, Groene Hart Hospital, Bleulandweg 10, 2803HH, Gouda, The Netherlands. 21. Department of Medical Oncology, Diakonessenhuis Utrecht, Postbus 80250, 3508TG, Utrecht, The Netherlands. 22. Department of Medical Oncology, Hospital Rivierenland, President Kennedylaan 1, 4002WP, Tiel, The Netherlands. 23. Department of Medical Oncology, Gelre Hospital, Postbus 9014, 7300DS, Apeldoorn, The Netherlands. 24. Department of Medical Oncology, Bravis Hospital Bergen op Zoom, Postbus 999, 4700AZ, Roosendaal, The Netherlands. 25. Department of Medical Oncology, VieCuri Medical Center, Postbus 1926, 5900BX, Venlo, The Netherlands. 26. Department of Medical Oncology, Zuyderland Medical Center Heerlen, Postbus 5500, 6130MB, Sittard-Geleen, The Netherlands. 27. Department of Medical Oncology, LangeLand Hospital, Postbus 3015, 2700KJ, Zoetermeer, The Netherlands. 28. Department of Medical Oncology, Tergooi, Van Riebeeckweg 212, 1213XZ, Hilversum, The Netherlands. 29. Department of Medical Oncology, ZorgSaam Hospital, Wielingenlaan 2, 4535PA, Terneuzen, The Netherlands. 30. Department of Medical Oncology, Meander Medical Center, Postbus 1502, 3800BM, Amersfoort, The Netherlands. 31. Department of Medical Oncology, Reinier de Graaf Gasthuis, Postbus 5011, 2600GA, Delft, The Netherlands. 32. Department of Medical Oncology, Hospital Rijnstate, Wagnerlaan 55, 6815AD, Arnhem, The Netherlands. 33. Department of Medical Oncology, Antonius Hospital Sneek, Postbus 20000, 8600BA, Sneek, The Netherlands. 34. Department of Medical Oncology, Amsterdam University Medical Center, VU Medical Center, P.O. Box 7057, 1007MB, Amsterdam, The Netherlands. 35. Department of Medical Oncology, Elkerliek Hospital, Postbus 98, 5700AB, Helmond, The Netherlands. 36. Department of Surgical Oncology, University Medical Center Utrecht, Utrecht University, Postbus 98, 5700AB, Utrecht, The Netherlands. 37. Utrecht Platform for Organoid Technology, University Medical Center Utrecht, Utrecht University, Postbus 98, 5700AB, Utrecht, The Netherlands. 38. Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, Postbus 22660, Amsterdam, The Netherlands. 39. Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, 3584CG, Utrecht, The Netherlands. M.Koopman-6@umcutrecht.nl.
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.
BACKGROUND: Metastatic colorectal cancerpatients 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 dMMRpatients, 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 dMMRpatients. Treated dMMRpatients 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.
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