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Classic Case

• phase II clinical study of pembrolizumab (MK-3475) for patients with microsatellite instability (MSI)

• NCT01876511

• Number of patients enrolled: 171

• Dosage: pembrolizumab 10 mg/kg every 14 days

• Enrollment criteria: Patients are grouped into dMMR (deficient in mismatch repair) and pMMR (proficient in mismatch repair) based on MMR test results.


irORR: immune-related objective response rate

irPFS: immune-related progression-free survival

mPFS: median progression-free survival

mOS: median overall survival

•Figure A: Real-time test results of serum marker CEA during pembrolizumab treatment. DMMR colorectal cancer group demonstrated significant and steady decrease.

Figure B: Radiographic responses to treatment with pembrolizumab, evaluated on the basis of Response Evaluation Criteria in Solid Tumors (RECIST).Tumor size decreased in patients with colorectal cancer and other solid tumor patients with dMMR.

Summary analysis:

-Prior clinical trial failures with immunosuppressive drugs such as pembrolizumab in colorectal cancer was due to the lack of consideration on genetic variations.

-In this study, successful genetic testing on MMR status led to ground-breaking clinical trial results that were published in the New England Journal of Medicine, reflecting the critical role of genetic testing in precision medicine.

-The preliminary clinical study results confirmed that the colorectal cancer patients and other solid-tumor patients with MMR gene deficiency had positive clinical response and favorable survival benefit from pembrolizumab treatment. On the opposite, colorectal cancer patients with the MMR gene intact would not benefit from this treatment.

-Both NCCN and ESMO guidelines strongly recommend that all patients with metastatic colorectal cancer undergo MMR/MSI testing for predicting the efficacy of immunotherapy.

Reference: N Engl J Med 2015; 372:2509-2520

Patients and families with hereditary colorectal cancer syndromes

•Patient Information:

•35-year-old female,diagnosed with Gardner syndrome

•Total colectomy 4 years ago

•Has a healthy 8-year-old daughter

•Genetic testing and results:

•Comprehensive Genetic Testing with 101-gene panel:APC R536X was found in both mother and daughter.

Daughter is a Gardner syndrome disease carrier.


[1] Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Colorectal. V1.2016. Jun 13. April 05.

Available from

[2] Kory W Jasperson et al. APC-Associated Polyposis Conditions.  In: Pagon RA. et al. editors. GeneReviews. PMID:20301519.

[3] Surveillance Research Program, National Cancer Institute SEER*Stat software ( seerstat) V 8.0.1, Nov 19, 2012.