Pembrolizumab’s Targeting of MSI-H-dMMR Colorectal Cancers More Effective Than Chemotherapy

The New England Journal of Medicine recently carried a report citing data from a Phase 3 clinical trial involving 307 people diagnosed with MSI-H-dMMR metastatic colorectal cancer.

MSI-H (high levels of microsatellite-instability) and dMMR tumors contain mutations that disrupt the repair of DNA within the cell. dMMR means deficient MisMatch Repair. Microsatellites are repeated sequences of DNA.

Normal cells have a system (the mismatch repair system) that repairs mistakes in cells when DNA is copied. MSI-H/dMMR may occur if a cell is defective and unable to repair the mistakes that are made during DNA copying. The result may be an accumulation of DNA errors that cause cancer.

Approximately five percent of colorectal cancer patients are diagnosed with MSI-H or dMMR tumors. MSI-H/dMMR can be either random or hereditary.

Participants who had no prior treatment for MSI-H or dMMR tumors were randomly administered 200 mg of pembrolizumab at three-week intervals or chemotherapy every two weeks. If patients in the chemotherapy group experienced disease progression they were allowed to join the pembrolizumab arm for treatment.

Results of the 2nd Interim Analysis

Pembrolizumab demonstrated its superiority to chemotherapy in progression-free survival at the median follow-up of thirty-two months (sixteen months vs. eight months).

Moving ahead to the two-year mark, the mean survival rate was thirteen months for the pembrolizumab group compared to ten months in the group receiving chemotherapy.

The pembrolizumab group logged an eighty-three percent overall response compared with a thirty-five percent ongoing response in the group receiving chemotherapy at the twenty-four-month mark.

Treatment-related Adverse Events (AE’s)

Twenty-two percent of patients had treatment-related AE’s of grade three or higher. This compares to sixty-six percent (and one death) in the chemotherapy cohort.

 And In Conclusion . . .

When compared to chemotherapy, pembrolizumab showed substantially higher rates of progression-free survival when administered as a first-line treatment for MSI-H-dMMR metastatic colorectal cancer. The recipients of the pembrolizumab therapy also had a lower rate of treatment-related AE’s. (see clinical trial NCT02563002 Keynote-177)

Based on the Keynote-177 clinical trial, in June 2020 the FDA approved pembrolizumab (Keytruda®) for treatment of patient metastatic MSI-H/dMMR colorectal cancer.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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