Abstract 368P
Background
Deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC) forms a distinct biological subgroup with prognostic, predictive and therapeutic implications compared to proficient MMR (pMMR) mCRC. It is unclear whether local therapy is similarly effective for dMMR mCRC patients. The aim of this study is to describe the recurrence-free survival (RFS) and overall survival (OS) after first-line local treatment in dMMR versus pMMR patients in the pre-immunotherapy era.
Methods
This is a retrospective study with data collected in the Netherlands Cancer Registry in 2015-2018. Local therapy included surgical resection of metastases, ablation and cytoreductive surgery (CRS) +/- HIPEC. RFS was defined as time from local mCRC treatment to progression of disease or death and OS to death or last follow-up alive. Subgroups of colorectal liver metastases (CRLM) treatment and CRS +/- HIPEC were analyzed.
Results
85 of 380 dMMR mCRC patients (22%) received local treatment versus 1089 of 2319 pMMR mCRC patients (47%). The table shows differences between both groups. Median RFS of all locally treated dMMR and pMMR patients was 11.3 versus 9.2 months, for CRLM-only treatment 9.6 versus 9.5 months and for CRS +/- HIPEC 26.6 versus 11.5 months. Median OS of dMMR and pMMR patients was 44.1 versus 43.3 months, for CRLM-only treatment the median was not reached versus 49.1 months and for CRS +/- HIPEC 44.1 versus 31.0 months. Table: 368P
Patient characteristics of pMMR and dMMR patients
| pMMR (N=1089) | dMMR (N=85) | |
| Mean age in years (SD) | 61.1 (10.1) | 62.8 (12.5) |
| Male | 627 (58%) | 33 (39%) |
| Sidedness | ||
| Left-sided | 440 (41%) | 14 (17%) |
| Right-sided | 288 (27%) | 66 (79%) |
| Rectosigmoid/rectum | 354 (33%) | 4 (5%) |
| Metastatic localization | ||
| Liver-only | 701 (64%) | 22 (26%) |
| Peritoneal involvement | 206 (19%) | 37 (44%) |
| Other | 182 (17%) | 26 (31%) |
| BRAF V600E status | ||
| Wildtype | 446 (95%) | 24 (47%) |
| Mutation | 22 (5%) | 27 (53%) |
| Unknown | 621 | 34 |
| RAS status | ||
| Wildtype | 301 (48%) | 28 (72%) |
| Mutation | 324 (52%) | 11 (28%) |
| Unknown | 464 | 46 |
| Peri-operative systemic therapy received | 558 (51%) | 29 (34%) |
| Local therapy | ||
| CRLM-only | 672 (62%) | 21 (25%) |
| CRS/HIPEC-only | 148 (14%) | 35 (41%) |
| Other | 269 (25%) | 29 (33%) |
Conclusions
A smaller proportion of dMMR patients received local treatment, and characteristics and treatment differed importantly. Despite, these findings indicate dMMR mCRC patients had at least comparable survival and suggest local treatment as valuable treatment option. It is uncertain how this relates to the long-term durable remissions seen with immunotherapy in this population. Further research is warranted whether local treatment, immunotherapy or a combination of both is preferred in first-line dMMR patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
UMC Utrecht.
Funding
Has not received any funding.
Disclosure
J. Roodhart: Financial Interests, Institutional, Research Grant: Bayer, BMS, Merck-Serono, Pierre Fabre, Servier, HUB 4 organoids, Cleara Biotech; Non-Financial Interests, Institutional, Advisory Board: ONCODE. C.J.A. Punt: Financial Interests, Institutional, Advisory Board: Nordic Pharma. I.H.J.T. de Hingh: Financial Interests, Institutional, Research Grant: Roche, RanD Biotech. M. Koopman: Financial Interests, Institutional, Advisory Board, advisory board and speaker: Pierre Fabre; Financial Interests, Institutional, Advisory Board: MSD, Bayer; Financial Interests, Institutional, Advisory Board, Advisory Board, speaker: Servier; Financial Interests, Institutional, Invited Speaker: Merck, BMS, Servier; Financial Interests, Institutional, Research Grant: Servier, Roche, Bayer, Bristol Myers Squibb, Merck, Personal Genomics Diagnostics, Sirtex, Pierre Fabre; Financial Interests, Institutional, Funding: Pierre Fabre, Amgen, Nordic Farma, Novartis, Merck, Servier, BMS; Non-Financial Interests, Leadership Role, vice-chair of DCCG: Dutch Colorectal Cancer Group; Non-Financial Interests, Advisory Role, Member of KWF scientific board: KWF; Non-Financial Interests, Other, ESMO faculty member for the Gastro-Intestinal Tumours – colorectal cancer: ESMO; Non-Financial Interests, Advisory Role, expert member of committee “regie op registers dure geneesmiddelen” ZINNL: ZiNNL; Non-Financial Interests, Advisory Role, CRC expert on Kanker.nl platform for answering online CRC questions of CRC (non) patients: Patient representative organisation (Kanker.nl); Non-Financial Interests, Leadership Role, chair of RWD & DH working group: ESMO; Other, Other, PI of the Dutch Prospective Colorectal Cancer Cohort study: PLCRC project. G. Vink: Financial Interests, Institutional, Research Grant: BMS, Merck, Servier, Personal Genome Diagnostics, Bayer, Sirtex, Pierre Fabre, Lilly. All other authors have declared no conflicts of interest.