European Commission Approves KEYTRUDA® (pembrolizumab) as First-Line Monotherapy for MSI-H/dMMR Metastatic Colorectal Cancer

January 26, 2021/BioValleyBIOON/--Merck & Co. recently announced that the European Commission (EC) has approved the anti-PD-1 therapy Keytruda (brand name: Keytruda; generic name: pembrolizumab), as a monotherapy for the first-line treatment of adult patients with metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer (mCRC).

In Europe, patients with MSI-H/dMMR mCRC have historically been limited to chemotherapy-containing regimens as first-line treatment and have faced poor outcomes. This approval marks the first gastrointestinal indication for Keytruda in Europe and establishes Keytruda as the first anti-PD-1/L1 therapy approved in Europe for these patients.

In the United States, the indication for Keytruda as a monotherapy in the first-line treatment of MSI-H/dMMR mCRC was approved in June 2020. Notably, Keytruda is the first anti-PD-1 monotherapy approved for the first-line treatment of MSI-H/dMMR mCRC, with the potential to transform the treatment paradigm for first-line management of MSI-H mCRC. In May 2017, Keytruda received U.S.FDAApproved, becoming the first MSI-H/dMMR-basedBiomarkersan anticancer drug for the treatment of patients with MSI-H or dMMR solid tumors, regardless ofTumorWhat is the type?

This approval is based on the results of the pivotal Phase 3 KEYNOTE-177 study. This study was the first positive head-to-head Phase 3 trial comparing monotherapy anti-PD-1 treatment with standard-of-care chemotherapy as first-line therapy for MSI-H or dMMR colorectal cancer. The data showed that,Compared with current standard-of-care chemotherapy(mFOLFOX6 or FOLFIRI, with or without bevacizumab or cetuximab, at the investigator’s discretion)Compared to，Keytruda monotherapy as first-line treatment significantly reduced the risk of disease progression or death by 40% (p=0.0004) and significantly doubled progression-free survival (median PFS: 16.5 months vs. 8.2 months).The results of this study have been published in the New England Journal of Medicine (NEJM); see:Pembrolizumab in Microsatellite-Instability–High Advanced Colorectal Cancer。

Colorectal Cancer (Image source: medicalnewstoday.com)

Colorectal cancer (CRC) is a cancer that originates in the colon or rectum, which are parts of the body’s digestive or gastrointestinal system. CRC is the third most common cancer worldwide and the second leading cause of cancer-related deaths. In 2018, it was estimated that there were nearly 850,000 new cases of CRC diagnosed globally, with over 880,000 deaths; Europe alone accounted for nearly 500,000 new cases. The 5-year survival rates for advanced/metastatic colon cancer and rectal cancer (Stage IV) are 14% and 15%, respectively.

Microsatellite Instability (MSI) is a change that occurs in the DNA of certain cells (such as tumor cells), in which the number of repeats of microsatellites (short, repetitive DNA sequences) differs fromHeredityThe number of repeats in DNA varies over time. Microsatellite instability may result from defective error-repair capacity during DNA replication in cells. This defect is also referred to as mismatch repair deficiency (dMMR). It is estimated that approximately 10–15% of CRC patients, upon testing,TumorAssessed as MSI-H or dMMR.

Patients with dMMR or MSI-H mCRC are unlikely to benefit from conventional chemotherapy regimens, typically have a very poor prognosis, and exhibit low survival rates. Therefore, routine testing for dMMR or MSI-H status should be performed in all CRC patients. In May 2017, Keytruda received U.S.FDAApproved, becoming the first MSI-H/dMMR-basedBiomarkersanticancer drugs for the treatment of patients with MSI-H or dMMR solid tumors, regardless ofTumorWhat is the type?

Keytruda is an anti-PD-(L)1 cancer immunotherapy. This class of therapies helps detect and combat tumor cells by enhancing the capabilities of the human immune system. Keytruda is an anti-PD-1 therapy that activates potentially affected pathways by blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2.TumorT lymphocytes of cells and healthy cells. To date, Keytruda has been approved for the treatment of various types of cancer.

Globally, more than 10 anti-PD-(L)1 therapies have been approved for marketing, with Keytruda emerging as the frontrunner. In 2019, its global sales reached $11.1 billion, representing a year-on-year growth of 58%. Previously, the pharmaceutical market research firm EvaluatePharma released a report predicting that Keytruda’s sales would reach $24.91 billion in 2026, making it the world’s best-selling drug.

MSD boasts the largest immuno-oncology clinical development program in the industry, with over 1,300Clinical TrialInvestigating Keytruda in Multiple TypesTumorand its role in the treatment context. The Keytruda clinical program aims to understand the drug’s role in cancer and identify factors that may predict patient benefit from Keytruda therapy, including exploring several differentBiomarkers(Bioon.com)

Original source: European Commissionapproves KEYTRUDA® (pembrolizumab) as First-Line Treatment in Adult Patients With Metastatic Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Colorectal Cancer