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. 2021 Jan;124(2):399-406.
doi: 10.1038/s41416-020-01076-0. Epub 2020 Oct 13.

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

G Emerens Wensink  1 , Marloes A G Elferink  2 , Anne M May  3 , Linda Mol  2 , Patricia A H Hamers  1 , Sandra D Bakker  4 , Geert-Jan Creemers  5 , Jan Willem B de Groot  6 , Gerty J de Klerk  7 , Brigitte C M Haberkorn  8 , Annebeth W Haringhuizen  9 , Ronald Hoekstra  10 , J Cornelis B Hunting  11 , Emile D Kerver  12 , Danielle Mathijssen-van Stein  13 , Marco B Polée  14 , Johannes F M Pruijt  15 , Patricia Quarles van Ufford-Mannesse  16 , Sandra Radema  17 , Ronald C Rietbroek  18 , Lieke H J Simkens  19 , Bea C Tanis  20 , Daan Ten Bokkel Huinink  21 , Manuel L R Tjin-A-Ton  22 , Cathrien S Tromp-van Driel  23 , Monique M Troost  24 , Agnes J van de Wouw  25 , Franchette W P J van den Berkmortel  26 , Anke J M van der Pas  27 , Ankie M T van der Velden  28 , Marjan A van Dijk  29 , Joyce M van Dodewaard-de Jong  30 , Edith B van Druten  31 , Theo van Voorthuizen  32 , Gerrit Jan Veldhuis  33 , Henk M W Verheul  34 , Hanneke J H M J Vestjens  25 , Jeroen Vincent  35 , Onno W Kranenburg  36   37 , Cornelis J A Punt  38 , Geraldine R Vink  1   2 , Jeanine M L Roodhart  1 , Miriam Koopman  39
Affiliations

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

G Emerens Wensink et al. Br J Cancer. 2021 Jan.

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.

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Conflict of interest statement

The authors declare no conflict of interest. J.W.B.G. Institutional financial instructs (IFI): BMS, Pierre Fabre, Roche, MSD, Shire, Amgen; M.K. IFI: Amgen, Bayer, BMS, Merck-Serono, Nordic Farma, Roche, Servier, Sirtex, Sanofi-Aventis; Non-financial interests (NFI): advisory role ZON-MW, daily board member DCCG, P.I. PLCRC; CJAP IFI: Amgen, Roche; J.M.L.R. IFI: Servier, Merck, Bayer; T.v.V. NFI: Pfizer, Ipsen, Astellas, Roche, Bayer; H.V. IFI: Immunovo, Glycostem, Roche; G.R.V. IFI: Servier, Bayer, Merck, BMS, Lilly. All grants were unrelated to the study and paid to the individual’s institution.

Figures

Fig. 1
Fig. 1. Flow diagram of Netherlands Cancer Registry (NCR) patients.
All NCR patients with histologically proven metastatic colorectal cancer (mCRC) were assessed for eligibility. Patients were excluded if mismatch repair (MMR) status was unknown or proficient MMR (pMMR) and if patients received immunotherapy during treatment. The final population-based cohort consists of 227 patients with deficient mismatch repair (dMMR) mCRC.
Fig. 2
Fig. 2. OS, OS1 and OS2 in mCRC patients with dMMR.
Predicted overall survival (OS) using Kaplan–Meier curves with confidence intervals, examined for the cohort as a whole and in patients who received systemic treatment. a OS from metastatic disease in the unselected dMMR cohort (n = 279), stratified by having received antitumour therapy (n = 207) versus no antitumour therapy (n = 72), b Overall survival from first-line systemic therapy initiation (OS1) in first-line patients (n = 170), c Overall survival from second-line systemic therapy initiation (OS2) in second-line patients (n = 70). The risk tables display the number of patients at risk and the number of censored patients. Median survival is indicated with a vertical dashed line in each plot and is indicated with 95% confidence interval lower and upper ranges in the legend.
See this image and copyright information in PMC

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