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 Rietbroek; Lieke 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

doi:10.1038/s41416-020-01076-0

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 journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	399-406
Number of pages	8
Journal	British Journal of Cancer
Volume	124
Issue number	2
Early online date	13 Oct 2020
DOIs	https://doi.org/10.1038/s41416-020-01076-0
Publication status	Published - Jan 2021

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10.1038/s41416-020-01076-0

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Wensink, G. E., Elferink, M. A. G., May, A. M., Mol, L., Hamers, P. A. H., Bakker, S. D., Creemers, G.-J., de Groot, J. W. B., de Klerk, G. J., Haberkorn, B. C. M., Haringhuizen, A. W., Hoekstra, R., Hunting, J. C. B., Kerver, E. D., Mathijssen-van Stein, D., Polée, M. B., Pruijt, J. F. M., Quarles van Ufford-Mannesse, P., Radema, S., ... Koopman, M. (2021). Survival of patients with deficient mismatch repair metastatic colorectal cancer in the pre-immunotherapy era. British Journal of Cancer, 124(2), 399-406. https://doi.org/10.1038/s41416-020-01076-0

@article{dff045db9dc84d529e0801cf823d9a85,

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

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.",

author = "Wensink, {G Emerens} and Elferink, {Marloes A G} and May, {Anne M} and Linda Mol and Hamers, {Patricia A H} and Bakker, {Sandra D} and Geert-Jan Creemers and {de Groot}, {Jan Willem B} and {de Klerk}, {Gerty J} and Haberkorn, {Brigitte C M} and Haringhuizen, {Annebeth W} and Ronald Hoekstra and Hunting, {J Cornelis B} and Kerver, {Emile D} and {Mathijssen-van Stein}, Danielle and Pol{\'e}e, {Marco B} and Pruijt, {Johannes F M} and {Quarles van Ufford-Mannesse}, Patricia and Sandra Radema and Rietbroek, {Ronald C} and Simkens, {Lieke H J} and Tanis, {Bea C} and {Ten Bokkel Huinink}, Daan and Tjin-A-Ton, {Manuel L R} and {Tromp-van Driel}, {Cathrien S} and Troost, {Monique M} and {van de Wouw}, {Agnes J} and {van den Berkmortel}, {Franchette W P J} and {van der Pas}, {Anke J M} and {van der Velden}, {Ankie M T} and {van Dijk}, {Marjan A} and {van Dodewaard-de Jong}, {Joyce M} and {van Druten}, {Edith B} and {van Voorthuizen}, Theo and {Jan Veldhuis}, Gerrit and Verheul, {Henk M W} and Vestjens, {Hanneke J H M J} and Jeroen Vincent and Kranenburg, {Onno W} and Punt, {Cornelis J A} and Vink, {Geraldine R} and Roodhart, {Jeanine M L} and Miriam Koopman",

year = "2021",

month = jan,

doi = "10.1038/s41416-020-01076-0",

language = "English",

volume = "124",

pages = "399--406",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Springer Nature",

number = "2",

}

Wensink, GE, Elferink, MAG, May, AM, Mol, L, Hamers, PAH, Bakker, SD, Creemers, G-J, de Groot, JWB, de Klerk, GJ, Haberkorn, BCM, Haringhuizen, AW, Hoekstra, R, Hunting, JCB, Kerver, ED, Mathijssen-van Stein, D, Polée, MB, Pruijt, JFM, Quarles van Ufford-Mannesse, P, Radema, S, Rietbroek, RC, Simkens, LHJ, Tanis, BC, Ten Bokkel Huinink, D, Tjin-A-Ton, MLR, Tromp-van Driel, CS, Troost, MM, van de Wouw, AJ, van den Berkmortel, FWPJ, van der Pas, AJM, van der Velden, AMT, van Dijk, MA, van Dodewaard-de Jong, JM, van Druten, EB, van Voorthuizen, T, Jan Veldhuis, G, Verheul, HMW, Vestjens, HJHMJ, Vincent, J, Kranenburg, OW, Punt, CJA, Vink, GR, Roodhart, JML & Koopman, M 2021, 'Survival of patients with deficient mismatch repair metastatic colorectal cancer in the pre-immunotherapy era', British Journal of Cancer, vol. 124, no. 2, pp. 399-406. https://doi.org/10.1038/s41416-020-01076-0

TY - JOUR

T1 - Survival of patients with deficient mismatch repair metastatic colorectal cancer in the pre-immunotherapy era

AU - Wensink, G Emerens

AU - Elferink, Marloes A G

AU - May, Anne M

AU - Mol, Linda

AU - Hamers, Patricia A H

AU - Bakker, Sandra D

AU - Creemers, Geert-Jan

AU - de Groot, Jan Willem B

AU - de Klerk, Gerty J

AU - Haberkorn, Brigitte C M

AU - Haringhuizen, Annebeth W

AU - Hoekstra, Ronald

AU - Hunting, J Cornelis B

AU - Kerver, Emile D

AU - Mathijssen-van Stein, Danielle

AU - Polée, Marco B

AU - Pruijt, Johannes F M

AU - Quarles van Ufford-Mannesse, Patricia

AU - Radema, Sandra

AU - Rietbroek, Ronald C

AU - Simkens, Lieke H J

AU - Tanis, Bea C

AU - Ten Bokkel Huinink, Daan

AU - Tjin-A-Ton, Manuel L R

AU - Tromp-van Driel, Cathrien S

AU - Troost, Monique M

AU - van de Wouw, Agnes J

AU - van den Berkmortel, Franchette W P J

AU - van der Pas, Anke J M

AU - van der Velden, Ankie M T

AU - van Dijk, Marjan A

AU - van Dodewaard-de Jong, Joyce M

AU - van Druten, Edith B

AU - van Voorthuizen, Theo

AU - Jan Veldhuis, Gerrit

AU - Verheul, Henk M W

AU - Vestjens, Hanneke J H M J

AU - Vincent, Jeroen

AU - Kranenburg, Onno W

AU - Punt, Cornelis J A

AU - Vink, Geraldine R

AU - Roodhart, Jeanine M L

AU - Koopman, Miriam

PY - 2021/1

Y1 - 2021/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85092338326&partnerID=8YFLogxK

U2 - 10.1038/s41416-020-01076-0

DO - 10.1038/s41416-020-01076-0

M3 - Article

C2 - 33046804

SN - 0007-0920

VL - 124

SP - 399

EP - 406

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 2

ER -

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

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