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

被引：21

作者：

Wensink, G. Emerens ^{[1
]}

Elferink, Marloes A. G. ^{[2
]}

May, Anne M. ^{[3
]}

Mol, Linda ^{[2
]}

Hamers, Patricia A. H. ^{[1
]}

Bakker, Sandra D. ^{[4
]}

Creemers, Geert-Jan ^{[5
]}

de Groot, Jan Willem B. ^{[6
]}

de Klerk, Gerty J. ^{[7
]}

Haberkorn, Brigitte C. M. ^{[8
]}

Haringhuizen, Annebeth W. ^{[9
]}

Hoekstra, Ronald ^{[10
]}

Hunting, J. Cornelis B. ^{[11
]}

Kerver, Emile D. ^{[12
]}

Mathijssen-van Stein, Danielle ^{[13
]}

Polee, Marco B. ^{[14
]}

Pruijt, Johannes F. M. ^{[15
]}

Quarles van Ufford-Mannesse, Patricia ^{[16
]}

Radema, Sandra ^{[17
]}

Rietbroek, Ronald C. ^{[18
]}

Simkens, Lieke H. J. ^{[19
]}

Tanis, Bea C. ^{[20
]}

ten Bokkel Huinink, Daan ^{[21
]}

Tjin-A-Ton, Manuel L. R. ^{[22
]}

Tromp-van Driel, Cathrien S. ^{[23
]}

Troost, Monique M. ^{[24
]}

van de Wouw, Agnes J. ^{[25
]}

van den Berkmortel, Franchette W. P. J. ^{[26
]}

van der Pas, Anke J. M. ^{[27
]}

van der Velden, Ankie M. T. ^{[28
]}

van Dijk, Marjan A. ^{[29
]}

van Dodewaard-de Jong, Joyce M. ^{[30
]}

van Druten, Edith B. ^{[31
]}

van Voorthuizen, Theo ^{[32
]}

Jan Veldhuis, Gerrit ^{[33
]}

Verheul, Henk M. W. ^{[34
]}

Vestjens, Hanneke J. H. M. J. ^{[25
]}

Vincent, Jeroen ^{[35
]}

Kranenburg, Onno W. ^{[36
,37
]}

Punt, Cornelis J. A. ^{[38
]}

Vink, Geraldine R. ^{[1
,2
]}

Roodhart, Jeanine M. L. ^{[1
]}

Koopman, Miriam ^{[1
]}

机构：

[1] Univ Utrecht, Univ Med Ctr Utrecht, Dept Med Oncol, Univ Weg 100, NL-3584 CG Utrecht, Netherlands

[2] Netherlands Comprehens Canc Org, Dept Res, Postbus 19079, NL-3501 DB Utrecht, Netherlands

[3] Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, POB 85500, NL-3508 GA Utrecht, Netherlands

[4] Zaans Med Ctr, Dept Med Onco, Postbus 210, NL-1500 EE Zaandam, Netherlands

[5] Catharina Hosp, Dept Med Oncol, Postbus 1350, NL-5602 ZA Eindhoven, Netherlands

[6] Isala Hosp, Dept Med Oncol, Dokter Heesweg 2, NL-8025 AB Zwolle, Netherlands

[7] Spaarne Gasthuis, Dept Med Oncol, Spaarnepoort 1, NL-2134 TM Hoofddorp, Netherlands

[8] Maasstad Hosp, Dept Med Oncol, Postbus 9100, NL-3007 AC Rotterdam, Netherlands

[9] Hosp Gelderse Vallei, Dept Med Oncol, Willy Brandtlaan 10, NL-6716 RP Ede, Netherlands

[10] Ziekenhuisgroep Twente, Dept Med Oncol, Postbus 7600, NL-7600 SZ Almelo, Netherlands

[11] Antonius Hosp, Dept Med Oncol, Postbus 2500, NL-3430 EM Nieuwegein, Netherlands

[12] OLVG, Dept Med Oncol, Oosterpark 9, NL-1091 AC Amsterdam, Netherlands

[13] Franciscus Gasthuis & Vlietland, Dept Med Oncol, Vlietlandpl, NL-3118 JH Schiedam, Netherlands

[14] Med Ctr Leeuwarden, Dept Med Oncol, Postbus 888, NL-8901 BR Leeuwarden, Netherlands

[15] Jeroen Bosch Hosp, Dept Med Oncol, Postbus 90153, NL-5200 ME Shertogenbosch, Netherlands

[16] HagaZiekenhuis, Dept Med Oncol, Els Borst Eilerspl 275, NL-2545 AA The Hague, Netherlands

[17] Radboud Univ Nijmegen, Dept Med Oncol, Med Ctr, Postbus 9101, NL-6500 HB Nijmegen, Netherlands

[18] Rode Kruis Hosp, Dept Med Oncol, Postbus 1074, NL-1940 EB Beverwijk, Netherlands

[19] Maxima Med Ctr, Dept Med Oncol, Postbus 90052, NL-5600 PD Eindhoven, Netherlands

[20] Groene Hart Hosp, Dept Med Oncol, Bleulandweg 10, NL-2803 HH Gouda, Netherlands

[21] Diakonessenhuis Utrecht, Dept Med Oncol, Postbus 80250, NL-3508 TG Utrecht, Netherlands

[22] Hosp Rivierenland, Dept Med Oncol, President Kennedylaan 1, NL-4002 WP Tiel, Netherlands

[23] Gelre Hosp, Dept Med Oncol, Postbus 9014, NL-7300 DS Apeldoorn, Netherlands

[24] Bravis Hosp Bergen Zoom, Dept Med Oncol, Postbus 999, NL-4700 AZ Roosendaal, Netherlands

[25] VieCuri Med Ctr, Dept Med Oncol, Postbus 1926, NL-5900 BX Venlo, Netherlands

[26] Zuyderland Med Ctr Heerlen, Dept Med Oncol, Postbus 5500, NL-6130 MB Geleen, Netherlands

[27] LangeLand Hosp, Dept Med Oncol, Postbus 3015, NL-2700 KJ Zoetermeer, Netherlands

[28] Tergooi, Dept Med Oncol, Riebeeckweg 212, NL-1213 XZ Hilversum, Netherlands

[29] ZorgSaam Hosp, Dept Med Oncol, Wielingenlaan 2, NL-4535 PA Terneuzen, Netherlands

[30] Meander Med Ctr, Dept Med Oncol, Postbus 1502, NL-3800 BM Amersfoort, Netherlands

[31] Reinier Graaf Gasthuis, Dept Med Oncol, Postbus 5011, NL-2600 GA Delft, Netherlands

[32] Hosp Rijnstate, Dept Med Oncol, Wagnerlaan 55, NL-6815 AD Arnhem, Netherlands

[33] Antonius Hosp Sneek, Dept Med Oncol, Postbus 20000, NL-8600 BA Sneek, Netherlands

[34] Univ Amsterdam, Med Ctr, Dept Med Oncol, Box 7057, NL-1007 MB Amsterdam, Netherlands

[35] Elkerliek Hosp, Dept Med Oncol, Postbus 98, NL-5700 AB Helmond, Netherlands

[36] Univ Utrecht, Univ Med Ctr Utrecht, Dept Surg Oncol, Postbus 98, NL-5700 AB Utrecht, Netherlands

[37] Univ Utrecht, Univ Med Ctr Utrecht, Utrecht Platform Organoid Technol, Postbus 98, NL-5700 AB Utrecht, Netherlands

[38] Univ Amsterdam, Med Centers, Dept Med Oncol, Postbus 22660, Amsterdam, Netherlands

来源：

BRITISH JOURNAL OF CANCER | 2021年 / 124卷 / 02期

关键词：

MICROSATELLITE INSTABILITY; POOLED ANALYSIS; BRAF MUTATION; PHASE-III; CAPECITABINE; OXALIPLATIN; MULTICENTER; BEVACIZUMAB; NIVOLUMAB; PROGNOSIS;

D O I：

10.1038/s41416-020-01076-0

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：399 / 406

页数：8

共 50 条

[1] 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
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Patricia Quarles van Ufford-Mannesse
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Ronald C. Rietbroek
Lieke H. J. Simkens
Bea C. Tanis
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