Targeted therapy is a precision medicine cancer treatment that uses drugs to target specific gene mutations or proteins that are involved in tumor development. Targeted therapies may be a form of chemotherapy or other cancer treating medications. Often targeted therapies are not use as a first round treatment option. Many are available only through clinical trials.

Targeted therapies are different from standard chemotherapy in multiple ways. Standard chemotherapies act on all rapidly dividing cancer and normal cells. Targeted therapies act on specific molecular targets related to cancer development. Targeted therapies often interact specifically with their target to block tumor cell proliferation as opposed to killing all dividing cells.

Lynch syndrome tumors often have high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR) status. Both MSI-H and dMMR in a tumor can influence treatment decision-making in patients with cancer.  Affects are seen in patients with Lynch syndrome, as well as patients with sporadic MSI-H/dMMR.

Chemotherapy efficacy:

Using adjuvant fluoropyrimidine monotherapy (such as 5-FU) does not appear to confer a benefit when treating stage II MSI-H/dMMR colon cancers.

Immunotherapy with PD-1 inhibitors:

PD-1 inhibitors (including Pembrolizumab, Nivolumab, and Ipilimumab) have been shown to confer treatment benefits to patients with MSI-H/dMMR tumors.  These are typically utilized in patients with advanced/metastatic disease.

In 2017, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) for the treatment of all MSI-H tumors. Since then, MSI testing of all tumors has become more common to see if people can be treated with pembrolizumab.

Clinical Trials:

Identifying new targeted therapies for MSI-H/dMMR cancers is an active area of research. Many associated clinical trials are underway worldwide.

Current clinical trials:

Note: this is not a comprehensive list of all currently available clinical trials in this area.  This list includes trials available at various centers across the U.S.

• CD24Fc With Ipilimumab and Nivolumab to Decrease irAE (CINDI) (CINDI) (NCT04060407)
• A Study of Pembrolizumab (MK-3475) in Pediatric Participants With an Advanced Solid Tumor or Lymphoma (MK-3475-051/KEYNOTE-051) (NCT02332668)
• Study of RP1 Monotherapy and RP1 in Combination With Nivolumab (NCT03767348)
• Study of TSR-042, an Anti-programmed Cell Death-1 Receptor (PD-1) Monoclonal Antibody, in Participants With Advanced Solid Tumors (GARNET) (NCT02715284)
• A Study of XmAb®22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors (DUET-4) (NCT03849469)
• A Study of XmAb®20717 in Subjects With Selected Advanced Solid Tumors (DUET-2) (NCT03517488)
• Nivolumab and Ipilimumab and Radiation Therapy in MSS and MSI High Colorectal and Pancreatic Cancer (NCT03104439)
• A Study of Nivolumab, Nivolumab Plus Ipilimumab, or Investigator's Choice Chemotherapy for the Treatment of Patients With Deficient Mismatch Repair (dMMR)/Microsatellite Instability High (MSI-H) Metastatic Colorectal Cancer (mCRC) (CheckMate 8HW) (NCT04008030)
• Avelumab in Patients With MSS, MSI-H and POLE-mutated Recurrent or Persistent Endometrial Cancer and of Avelumab/Talazoparib and Avelumab/Axitinib in Patients With MSS Recurrent or Persistent Endometrial Cancer (NCT02912572)
• Anti-PD-1 +/- RT for MSI-H Solid Tumors (NCT04001101)
• Study of Nivolumab and Relatlimab in Advanced Mismatch Repair Deficient Cancers Resistant to Prior PD-(L)1 Inhibitor (NCT03607890)
• M7824 in Patients With Metastatic Colorectal Cancer or With Advanced Solid Tumors With Microsatellite Instability (NCT03436563)
• Study of Pembrolizumab Following Surgery in Patients With Microsatellite Instability (MSI-H) Solid Tumors (NCT03832569)