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Association details:
Biomarker:MSI-H/dMMR
Cancer:Colorectal Cancer
Drug Class:Immunotherapy
Direction:Sensitive
Evidence:
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Transcriptomic Signatures of MSI-High Metastatic Colorectal Cancer Predict Efficacy of Immune Checkpoint Inhibitors

Published date:
09/15/2023
Excerpt:
In two cohorts of patients with MSI mCRC treated with ICI...In multivariate analysis, PFS was still significantly longer in patients belonging to cluster B [HR, 0.19; 95% confidence interval (CI), 0.08-0.45; P < 0.001] and cluster C (HR, 0.25; 95% CI, 0.10-0.59; P = 0.02), compared with patients belonging to cluster A. The association of this clustering with PFS under ICI was confirmed in the validation cohort.
DOI:
10.1158/1078-0432.CCR-22-3964
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Neoadjuvant Immune Checkpoint Inhibitor Therapy for Localized Deficient Mismatch Repair Colorectal Cancer

Published date:
09/07/2023
Excerpt:
Multiple prospective phase 2 studies in limited numbers of patients with localized dMMR CRC demonstrate high complete clinical and pathological response rates (60%-100%) to neoadjuvant ICIs...Given the median follow-up of 12 to 25 months in these studies, longer-term monitoring is needed to determine the durability of response and to ensure that oncologic outcomes...While this review found that early results of neoadjuvant immunotherapy for localized dMMR CRC show high rates of major and complete pathological response, longer-term follow-up data are needed to ensure that oncologic outcomes are not compromised and are ideally improved. Neoadjuvant ICI therapy in localized dMMR CRC represents a potential paradigm shift with implications for organ preservation.
DOI:
10.1001/jamaoncol.2023.3323
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Efficacy of Immune Checkpoint Inhibition and Cytotoxic Chemotherapy in Mismatch Repair-Deficient and Microsatellite Instability-High Pancreatic Cancer: Mayo Clinic Experience

Published date:
08/25/2023
Excerpt:
In the palliative setting, excellent responses to ICI were seen, with overall response rate (ORR) of 75% (20% complete response). Median time to disease progression was not reached. Response rates to cytotoxic chemotherapy in the palliative setting were poor, with 30% ORR and median time to progression of 4 months....Our data argue for the preferential use of ICI over cytotoxic chemotherapy in any patient with dMMR/MSI-H PC requiring systemic therapy, including in the metastatic and adjuvant/neoadjuvant settings.
DOI:
10.1200/PO.22.00706
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Outcome of Patients With Early-Stage Mismatch Repair Deficient Colorectal Cancer Receiving Neoadjuvant Immunotherapy: A Systematic Review

Published date:
08/18/2023
Excerpt:
We conducted a systematic review to evaluate the outcome of patients with early-stage (stages I-III) mismatch repair deficient (dMMR) colorectal cancer (CRC) receiving neoadjuvant immunotherapy (NIT) with immune checkpoint inhibitor (ICI)-based regimens....The CR rate (pCR + cCR) in the overall population was 72% (305 of 423)....NIT in patients with early-stage dMMR CRC is associated with a high response rate, low primary resistance to immunotherapy and cancer recurrence rate, and an excellent safety profile.
DOI:
10.1200/PO.23.00182 JCO
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Immunotherapy for localized MSI-H colorectal cancer: Characterizing endoscopic and imaging response.

Published date:
05/25/2023
Excerpt:
The best endoscopic response was complete response (CR) in 13 of 30 (43%) patients, which was achieved after a median of 6 cycles….Nevertheless, immunotherapy was associated with deep and durable responses in most patients with localized MSI-H CRC.
DOI:
10.1200/JCO.2023.41.16_suppl.3610
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Efficacy and safety of neoadjuvant immune checkpoint inhibitors in patients with localized mismatch repair deficient colorectal cancer: A systematic review

Published date:
01/17/2023
Excerpt:
Neoadjuvant therapy with ICIs results in a remarkably high rate of clinical and pathological tumor regression with negligible safety concerns in patients with dMMR localized CRC.
DOI:
10.1200/JCO.2023.41.3_suppl.149
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Immune checkpoint inhibitors for patients with isolated peritoneal carcinomatosis from dMMR/MSI-H colorectal cancer, a BIG-RENAPE collaboration

Published date:
10/18/2022
Excerpt:
Among 45 patients included, we observed 11 complete responses and 10 partial responses for an overall response rate iRECIST of 46%...These results demonstrate long-term benefit of immune checkpoint inhibitors for patients with isolated PC from MSI/dMMR mCRC.
DOI:
10.1016/j.dld.2022.09.015
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Anti PD-1 monoclonal antibody in patients with MSI-high and/or high tumor mutational burden for solid malignancies.

Published date:
05/26/2022
Excerpt:
Retrospective analysis of 16 patients (pts) who received 18 CPI-based therapies between October 2017 and February 2022. MSI-H and TMB status was assessed by CARIS, Guardant360 or INVITAE genetic testing…. 15 pts were evaluable for response with an ORR of 33%, including 33% among pts with CRC and 27% for non-CRC malignancies....We identify a higher incidence of SD rates among CRC pts (67% vs. 18% non-CRC).
DOI:
10.1200/JCO.2022.40.16_suppl.e15539
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Immunotherapy for microsatellite-instability-high advanced colorectal cancer

Published date:
03/25/2022
Excerpt:
Neoadjuvant immunotherapy in MSI-H advantaged population can achieve high rates of pathological complete remission (pCR) and clinical complete remission (cCR).
DOI:
10.3760/cma.j.cn441530-20220118-00025
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Tumor copy-number alterations predict response to immune-checkpoint-blockade in gastrointestinal cancer

Published date:
08/13/2020
Excerpt:
Since MSI/MMR and PD-L1 expression have emerged as potential predictive biomarkers for PD-1/PD-L1 blockade, we examined the correlation between MSI/MMR or PD-L1 and the clinical benefit in GI cancer patients. Our data show that MSI-H/dMMR patients experienced a significantly higher DCB rate (59.1%) than MSI-L/MSS/pMMR patients (28.6%, p=0.022), while no association was found between PD-L1 positivity and the efficacy of ICB therapy in our cohort (online supplementary table S2).
DOI:
10.1136/jitc-2019-000374