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| Profile Name | MSH6 negative |
| Gene Variant Detail | |
| Relevant Treatment Approaches | PD-L1/PD-1 antibody Ipilimumab + Nivolumab |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| MSH6 negative | ovary epithelial cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as systemic therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | FDA approved - On Companion Diagnostic | Actionable | In a Phase I trial (GARNET) that supported FDA approval, Jemperli (dostarlimab-gxly) treatment demonstrated acceptable safety profile, and resulted in an objective response rate of 42.3% (30/71, 9 complete responses, 21 partial responses), with a median duration of response not reached in patients with recurrent or advanced endometrial cancer harboring mismatch repair deficiency (dMMR) as confirmed by a loss of MLH1, PMS2, MSH2, or MSH6 expression in an FDA-approved IHC test (PMID: 33001143; NCT02715284). | detail... 33001143 detail... |
| MSH6 negative | testicular germ cell cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as a third-line therapy for metastatic testicular germ cell cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | vulva cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as a second-line therapy for patients with MSI high or dMMR (often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) vulva cancer (NCCN.org). | detail... |
| MSH6 negative | endometrial carcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as first-line or subsequent-line therapy for patients with recurrent or metastatic endometrial carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | endometrial carcinoma | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as first-line or second-line therapy for patients with high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent endometrial carcinoma (NCCN.org). | detail... |
| MSH6 negative | endometrial carcinoma | sensitive | PD-L1/PD-1 antibody | Nivolumab | Guideline | Actionable | Opdivo (nivolumab) is included in guidelines as a second-line or subsequent-line therapy for patients with high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent endometrial carcinoma (NCCN.org). | detail... |
| MSH6 negative | Advanced Solid Tumor | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | FDA approved - On Companion Diagnostic | Actionable | In a Phase I trial (GARNET) that supported FDA aproval, Jemperli (dostarlimab-gxly) treatment demonstrated acceptable safety profile, and resulted in an objective response rate of 41.6% (87/209), with a median duration of response not reached in patients with advanced mismatch repair deficient (dMMR) solid tumors, as indicated by a loss of MLH1, PMS2, MSH2, or MSH6 expression in an FDA-approved IHC test (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 2564-2564; NCT02715284). | detail... detail... detail... |
| MSH6 negative | esophagus adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as first-line, second-line, or subsequent therapy for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) esophageal adenocarcinoma that are unresectable, locally advanced, recurrent, or metastatic (NCCN.org). | detail... |
| MSH6 negative | gastroesophageal junction adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as first-line, second-line, or subsequent therapy for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) gastroesophageal junction cancer that are unresectable, locally advanced, recurrent, or metastatic (NCCN.org). | detail... |
| MSH6 negative | stomach cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as first-line, second-line, or subsequent therapy for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) stomach cancer that are unresectable, locally advanced, recurrent, or metastatic (NCCN.org). | detail... |
| MSH6 negative | penile cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as subsequent-line systemic therapy for metastatic/recurrent penile cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | neuroendocrine tumor | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) locally advanced or metastatic well-differentiated, Grade 3 neuroendocrine tumors or unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, or mixed neuroendocrine/non-neuroendocrine neoplasms who have progressed on or following prior treatment (NCCN.org). | detail... |
| MSH6 negative | chondrosarcoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as systemic therapy for metastatic chondrosarcoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | osteosarcoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as systemic therapy for metastatic osteosarcoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | Ewing sarcoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as systemic therapy for metastatic Ewing sarcoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | chordoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as systemic therapy for metastatic chordoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | colorectal cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | FDA approved | Actionable | In a Phase III (KEYNOTE-177) trial that supported FDA approval, Keytruda (pembrolizumab) treatment as first-line therapy significantly improved median progression-free survival (16.5 vs 8.2 mo, HR=0.60, p=0.0002) compared to chemotherapy in patients with advanced microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) colorectal cancer (PMID: 33264544; NCT02563002). | 33264544 detail... |
| MSH6 negative | breast cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines for patients with metastatic or unresectable breast cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) who have progressed on or following prior treatment (NCCN.org). | detail... |
| MSH6 negative | colon cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | prostate adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as a second-line therapy for patients with advanced or metastatic prostate adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | small intestine adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as an initial therapy for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | small intestine adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Nivolumab | Guideline | Actionable | Opdivo (nivolumab) is included in guidelines as an initial therapy for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | small intestine adenocarcinoma | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Guideline | Actionable | Opdivo (nivolumab) in combination with Yervoy (ipilimumab) is included in guidelines as an initial therapy for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | small intestine adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as a subsequent therapy for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | rectum cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | rectum cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as a preferred primary therapy for advanced or metastatic rectum cancer patients with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | rectum cancer | sensitive | PD-L1/PD-1 antibody | Nivolumab | Guideline | Actionable | Opdivo (nivolumab) is included in guidelines as a primary therapy for advanced or metastatic rectum cancer patients with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | rectum cancer | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Guideline | Actionable | Opdivo (nivolumab) in combination with Yervoy (ipilimumab) is included in guidelines as a primary therapy for advanced or metastatic rectum cancer patients with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | hepatocellular carcinoma | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) hepatocellular carcinoma (NCCN.org). | detail... |
| MSH6 negative | endometrial carcinoma | sensitive | PD-L1/PD-1 antibody | Avelumab | Guideline | Actionable | Bavencio (avelumab) is included in guidelines as a second-line or subsequent-line therapy for patients with high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent endometrial carcinoma (NCCN.org). | detail... |
| MSH6 negative | intrahepatic cholangiocarcinoma | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy (category 2B) for patients with biliary tract cancer with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including intrahepatic cholangiocarcinoma (NCCN.org). | detail... |
| MSH6 negative | extrahepatic bile duct carcinoma | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy (category 2B) for patients with biliary tract cancer with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including extrahepatic cholangiocarcinoma (NCCN.org). | detail... |
| MSH6 negative | gallbladder cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy (category 2B) for patients with biliary tract cancer with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including gallbladder cancer (NCCN.org). | detail... |
| MSH6 negative | gallbladder cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as primary therapy and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including gallbladder cancer (NCCN.org). | detail... |
| MSH6 negative | intrahepatic cholangiocarcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as primary therapy and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including intrahepatic cholangiocarcinoma (NCCN.org). | detail... |
| MSH6 negative | extrahepatic bile duct carcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as primary therapy and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including extrahepatic cholangiocarcinoma (NCCN.org). | detail... |
| MSH6 negative | Advanced Solid Tumor | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | FDA approved | Actionable | In a combined analysis of 5 trials that supported FDA approval, Keytruda (pembrolizumab) therapy resulted in an objective response rate of 39.6% (59/149) in advanced solid tumor patients with high levels of microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (PMID: 30787022; NCT01876511, NCT02460198, NCT01848834, NCT02054806, NCT02628067). | detail... 30787022 |
| MSH6 negative | colon cancer | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Guideline | Actionable | Opdivo (nivolumab), in combination with Yervoy (ipilimumab), is included in guidelines as primary or subsequent therapy for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | colon cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as preferred primary or subsequent therapy for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | colon cancer | sensitive | PD-L1/PD-1 antibody | Nivolumab | Guideline | Actionable | Opdivo (nivolumab) is included in guidelines as primary or subsequent therapy for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | ovary epithelial cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as systemic therapy for patients with recurrent or advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | stomach cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced or metastatic gastric cancer with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | ovarian germ cell cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as recurrence therapy for patients with malignant ovarian germ cell tumors with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | esophagus adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | gastroesophageal junction adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | colorectal cancer | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | FDA approved | Actionable | In a Phase II (CheckMate 142) trial that supported FDA approval, Opdivo (nivolumab) and Yervoy (ipilimumab) combination treatment resulted in an objective response rate of 54.6% (65/119, 4 complete response, 61 partial response) and disease control over 12 weeks in 80% of patients with microsatellite instability-high (MSI-H) or DNA mismatch repair-deficient (dMMR, defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) metastatic colorectal cancer (PMID: 29355075; NCT02060188). | detail... detail... 29355075 |
| MSH6 negative | colorectal cancer | sensitive | PD-L1/PD-1 antibody | Nivolumab | FDA approved | Actionable | In a Phase II trial (CheckMate 142) that supported FDA approval, treatment with Opdivo (nivolumab) resulted in an objective response rate of 36% (19/53, 1 complete response, 18 partial responses) and disease control for 12 weeks or more in 70% (37/53) of patients with microsatellite instability-high (MSI-H) or DNA mismatch repair-deficient (dMMR, defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) metastatic colorectal cancer (PMID: 28734759; NCT02060188). | 28734759 detail... detail... |
| MSH6 negative | Adenocarcinoma of Unknown Primary | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines for patients with adenocarcinoma of unknown primary with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | Squamous Cell Carcinoma of Unknown Primary | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines for patients with squamous cell carcinoma of unknown primary with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | Adenocarcinoma of Unknown Primary | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines for patients with adenocarcinoma of unknown primary with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | endometrial carcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | FDA approved - On Companion Diagnostic | Actionable | In a Phase II trial (KEYNOTE-158) that supported FDA approval, Keytruda (pembrolizumab) treatment resulted in an objective response rate of 48% (38/79, 11 complete responses, 27 partial responses) in patients with advanced microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) endometrial carcinoma, with a median progression-free survival of 13.1 months (PMID: 34990208; NCT02628067). | detail... detail... 34990208 |
| MSH6 negative | pancreatic adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as first-line or subsequent therapy for patients with locally advanced, metastatic, or recurrent pancreatic adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | ampulla of Vater adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as first-line or subsequent therapy for metastatic ampullary adenocarcinoma patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | ampulla of Vater adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for metastatic ampullary adenocarcinoma patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | ampulla of Vater adenocarcinoma | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Guideline | Actionable | Opdivo (nivolumab) and Yervoy (ipilimumab) combination therapy is included in guidelines as first-line or subsequent therapy for metastatic ampullary adenocarcinoma patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | rectum cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Phase II | Actionable | In a Phase II trial, neoadjuvant Jemperli (dostarlimab-gxly) treatment resulted in an objective response of 100% (12/12, all complete responses) in patients with stage II or III rectal cancer with deficient mismatch repair (dMMR) as defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC (PMID: 35660797; NCT04165772). | 35660797 |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Avelumab | Guideline | Actionable | Bavencio (avelumab) is included in guidelines for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) endometrial cancer who have failed platinum-based therapy (PMID: 35690222; ESMO.org). | 35690222 detail... |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Durvalumab | Guideline | Actionable | Imfinzi (durvalumab) is included in guidelines for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) endometrial cancer who have failed platinum-based therapy (PMID: 35690222; ESMO.org). | detail... 35690222 |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines for patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) endometrial cancer who have failed platinum-based therapy (PMID: 35690222; ESMO.org). | detail... 35690222 |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) endometrial cancer who have failed platinum-based therapy (PMID: 35690222; ESMO.org). | 35690222 detail... |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Durvalumab | Phase II | Actionable | In a Phase II trial (PHAEDRA), Imfinzi (durvalumab) treatment resulted in superior objective tumor response rate (47%, 17/36, 6 complete responses, 11 partial responses (PR) vs 3%, 1/35, 1 PR) and median progression-free survival (8.3 vs 1.8 mo) in patients with mismatch repair deficient (dMMR, defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) advanced endometrial cancer compared to mismatch repair proficient patients (PMID: 34103352; NCT03015129). | 34103352 |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Avelumab | Phase II | Actionable | In a Phase II trial, Bavencio (avelumab) treatment resulted in an objective response rate of 26.7% (4/15, 1 complete response, 3 partial responses) and 6-month progression-free survival rate of 40% (6/15) in patients with mismatch repair deficient (dMMR, defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent or persistent endometrial cancer (PMID: 31461377; NCT02912572). | 31461377 |
| MSH6 negative | stomach cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as second-line therapy for patients with advanced or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) gastric cancer (PMID: 35914639; ESMO.org). | 35914639 detail... |
| MSH6 negative | gastroesophageal junction adenocarcinoma | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Phase II | Actionable | In a Phase II trial (NEONIPIGA), neoadjuvant Opdivo (nivolumab) and Yervoy (ipilimumab) followed by surgery led to a pathological complete response in 58.6% (17/29) of patients with resectable gastric/gastroesophageal junction adenocarcinoma with high microsatellite instability or deficient mismatch repair (dMMR) (defined by loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), and 30/31 patients in the per-protocol group were alive and progression-free at the time of analysis (PMID: 35969830; NCT0400626). | 35969830 |
| MSH6 negative | gastric adenocarcinoma | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Phase II | Actionable | In a Phase II trial (NEONIPIGA), neoadjuvant Opdivo (nivolumab) and Yervoy (ipilimumab) followed by surgery led to a pathological complete response in 58.6% (17/29) of patients with resectable gastric/gastroesophageal junction adenocarcinoma with high microsatellite instability or deficient mismatch repair (dMMR) (defined by loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), and 30/31 patients in the per-protocol group were alive and progression-free at the time of analysis (PMID: 35969830; NCT0400626). | 35969830 |
| MSH6 negative | cervical cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as preferred second-line or subsequent therapy for patients with cervical cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | cholangiocarcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as second or late-line therapy for patients with cholangiocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (PMID: 36372281; ESMO.org). | detail... 36372281 |
| MSH6 negative | Cancer of Unknown Primary | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as second-line therapy for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) cancer of unknown primary (CUP), or as first-line therapy for patients with MSI-H or dMMR colon-like CUP (PMID: 36563965; ESMO.org). | detail... 36563965 |
| MSH6 negative | stomach cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Phase II | Actionable | In a Phase II trial (KEYNOTE-158), Keytruda (pembrolizumab) treatment resulted in an objective response rate of 31.0% (13/42, 4 complete responses and 9 partial responses), a duration of response that was not reached, a median progression-free survival of 3.2 mo, and a median overall survival of 11.0 mo in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR, defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) gastric cancer (PMID: 35680043; NCT02628067). | 35680043 |
| MSH6 negative | small intestine cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Phase II | Actionable | In a Phase II trial (KEYNOTE-158), Keytruda (pembrolizumab) treatment resulted in an objective response rate of 48.0% (12/25, 3 complete responses and 8 partial responses), a duration of response and a median overall survival that was not reached, and a median progression-free survival of 23.4 mo in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR, defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) small intestine cancer (PMID: 35680043; NCT02628067). | 35680043 |
| MSH6 negative | ovarian cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Phase II | Actionable | In a Phase II trial (KEYNOTE-158), Keytruda (pembrolizumab) treatment resulted in an objective response rate of 33.3% (8/24, 3 complete responses and 5 partial responses), a duration of response that was not reached, a median progression-free survival of 2.2 mo, and a median overall survival of 33.6 mo in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR, defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) ovarian cancer (PMID: 35680043; NCT02628067). | 35680043 |
| MSH6 negative | biliary tract cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Phase II | Actionable | In a Phase II trial (KEYNOTE-158), Keytruda (pembrolizumab) treatment resulted in an objective response rate of 40.9% (9/22, 3 complete responses and 6 partial responses), a duration of response of 30.5 mo, a median progression-free survival of 4.2 mo, and a median overall survival of 19.4 mo in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR, defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) biliary tract cancer (PMID: 35680043; NCT02628067). | 35680043 |
| MSH6 negative | pancreatic cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Phase II | Actionable | In a Phase II trial (KEYNOTE-158), Keytruda (pembrolizumab) treatment resulted in an objective response rate of 18.2% (4/22, 1 complete response and 3 partial responses), a duration of response that was not reached, a median progression-free survival of 2.1 mo, and a median overall survival of 3.7 mo in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR, defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) pancreatic cancer (PMID: 35680043; NCT02628067). | 35680043 |
| MSH6 negative | colorectal cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as first-line therapy for patients with metastatic colorectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (PMID: 36307056; ESMO.org). | 36307056 detail... |
| MSH6 negative | colorectal cancer | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Guideline | Actionable | Yervoy (ipilimumab) in combination with Opdivo (nivolumab) is included in guidelines as second-line therapy for patients with metastatic colorectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (PMID: 36307056; ESMO.org). | 36307056 detail... |
| MSH6 negative | esophagus squamous cell carcinoma | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | esophagus squamous cell carcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as second-line or subsequent therapy for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) esophageal squamous cell carcinoma that are unresectable, locally advanced, recurrent, or metastatic (NCCN.org). | detail... |
| MSH6 negative | pancreatic adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for patients with locally advanced, metastatic, or recurrent pancreatic adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) who have not received prior immunotherapy (NCCN.org). | detail... |
| MSH6 negative | medullary thyroid carcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines for patients with medullary thyroid carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) after progression on prior treatment (NCCN.org). | detail... |
| MSH6 negative | papillary thyroid carcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines for patients with papillary thyroid carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) after progression on prior treatment (NCCN.org). | detail... |
| MSH6 negative | follicular thyroid carcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines for patients with follicular thyroid carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) after progression on prior treatment (NCCN.org). | detail... |
| MSH6 negative | oncocytic carcinoma of the thyroid | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines for patients with Hurthle cell thyroid carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) after progression on prior treatment (NCCN.org). | detail... |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Carboplatin + Dostarlimab-gxly + Paclitaxel | Phase III | Actionable | In a Phase III trial (RUBY), Jemperli (dostarlimab-gxly) plus carboplatin and paclitaxel followed by Jemperli (dostarlimab-gxly) improved 24-month progression-free survival (61.4% vs 15.7%, HR 0.28, p<0.001) compared to placebo in patients with advanced or recurrent mismatch repair-deficient (dMMR, as indicated by a loss of MLH1, PMS2, MSH2, or MSH6 expression in an FDA-approved IHC test) or microsatellite instability-high (MSI-H) endometrial cancer (PMID: 36972026; NCT03981796). | 36972026 |
| MSH6 negative | bone cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as a systemic therapy for patients with unresectable or metastatic bone cancer with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | pancreatic cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as second or later-line therapy for patients with metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) pancreatic cancer (PMID: 37678671; ESMO.org). | detail... 37678671 |
| MSH6 negative | esophagus adenocarcinoma | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Guideline | Actionable | Opdivo (nivolumab), in combination with Yervoy (ipilimumab), is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | esophagus adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Fluorouracil + Nivolumab + Oxaliplatin | Guideline | Actionable | Opdivo (nivolumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | esophagus squamous cell carcinoma | sensitive | PD-L1/PD-1 antibody | Fluorouracil + Nivolumab + Oxaliplatin | Guideline | Actionable | Opdivo (nivolumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophagus squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | esophagus adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Capecitabine + Nivolumab + Oxaliplatin | Guideline | Actionable | Opdivo (nivolumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | esophagus squamous cell carcinoma | sensitive | PD-L1/PD-1 antibody | Capecitabine + Nivolumab + Oxaliplatin | Guideline | Actionable | Opdivo (nivolumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophagus squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | gastroesophageal junction adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Capecitabine + Nivolumab + Oxaliplatin | Guideline | Actionable | Opdivo (nivolumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | esophagus adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Fluorouracil + Oxaliplatin + Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | esophagus squamous cell carcinoma | sensitive | PD-L1/PD-1 antibody | Fluorouracil + Oxaliplatin + Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophagus squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | gastroesophageal junction adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Fluorouracil + Oxaliplatin + Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | esophagus adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Capecitabine + Oxaliplatin + Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | esophagus squamous cell carcinoma | sensitive | PD-L1/PD-1 antibody | Capecitabine + Oxaliplatin + Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophagus squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | gastroesophageal junction adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Capecitabine + Oxaliplatin + Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | esophagus squamous cell carcinoma | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Guideline | Actionable | Opdivo (nivolumab), in combination with Yervoy (ipilimumab), is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophagus squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | gastroesophageal junction adenocarcinoma | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Guideline | Actionable | Opdivo (nivolumab), in combination with Yervoy (ipilimumab), is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | stomach cancer | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Guideline | Actionable | Opdivo (nivolumab), in combination with Yervoy (ipilimumab), is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | stomach cancer | sensitive | PD-L1/PD-1 antibody | Fluorouracil + Nivolumab + Oxaliplatin | Guideline | Actionable | Opdivo (nivolumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | stomach cancer | sensitive | PD-L1/PD-1 antibody | Capecitabine + Nivolumab + Oxaliplatin | Guideline | Actionable | Opdivo (nivolumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | stomach cancer | sensitive | PD-L1/PD-1 antibody | Fluorouracil + Oxaliplatin + Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | stomach cancer | sensitive | PD-L1/PD-1 antibody | Capecitabine + Oxaliplatin + Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | stomach cancer | sensitive | PD-L1/PD-1 antibody | Durvalumab + Tremelimumab | Guideline | Actionable | Imfinzi (durvalumab), in combination with Imjudo (tremelimumab, is included in guidelines as neoadjuvant therapy for patients with gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | gastroesophageal junction adenocarcinoma | sensitive | PD-L1/PD-1 antibody | Durvalumab + Tremelimumab | Guideline | Actionable | Imfinzi (durvalumab), in combination with Imjudo (tremelimumab), is included in guidelines as neoadjuvant therapy for patients with gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | sarcoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as systemic therapy for soft tissue sarcoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), regardless of sarcoma sub-type (NCCN.org). | detail... |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Dostarlimab-gxly | Guideline | Actionable | Jemperli (dostarlimab-gxly) is included in the Pan-Asian Guidelines Adaptation (PAGA) for patients with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent or advanced endometrial cancer who have failed prior platinum-based chemotherapy (PMID: 36696825; ESMO.org). | 36696825 detail... |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Immune checkpoint inhibitor monotherapy including Keytruda (pembrolizumab) is included in the Pan-Asian Guidelines Adaptation (PAGA) for patients with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent or metastatic endometrial cancer who have failed prior platinum-based chemotherapy (PMID: 36696825; ESMO.org). | detail... 36696825 |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Avelumab | Guideline | Actionable | Immune checkpoint inhibitor monotherapy including Bavencio (avelumab) is included in the Pan-Asian Guidelines Adaptation (PAGA) for patients with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent or metastatic endometrial cancer who have failed prior platinum-based chemotherapy (PMID: 36696825; ESMO.org). | detail... 36696825 |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Durvalumab | Guideline | Actionable | Immune checkpoint inhibitor monotherapy including Imfinzi (durvalumab) is included in the Pan-Asian Guidelines Adaptation (PAGA) for patients with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent or metastatic endometrial cancer who have failed prior platinum-based chemotherapy (PMID: 36696825; ESMO.org). | 36696825 detail... |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Nivolumab | Guideline | Actionable | Immune checkpoint inhibitor monotherapy including Opdivo (nivolumab) is included in the Pan-Asian Guidelines Adaptation (PAGA) for patients with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent or metastatic endometrial cancer who have failed prior platinum-based chemotherapy (PMID: 36696825; ESMO.org). | detail... 36696825 |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Atezolizumab | Guideline | Actionable | Immune checkpoint inhibitor monotherapy including Tecentriq (atezolizumab) is included in the Pan-Asian Guidelines Adaptation (PAGA) for patients with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent or metastatic endometrial cancer who have failed prior platinum-based chemotherapy (PMID: 36696825; ESMO.org). | detail... 36696825 |
| MSH6 negative | colorectal cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in the Pan-Asian Guidelines Adaptation (PAGA) as first-line therapy for patients with advanced or metastatic colorectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (PMID: 37236086; ESMO.org). | detail... 37236086 |
| MSH6 negative | colorectal cancer | sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Guideline | Actionable | Yervoy (ipilimumab) in combination with Opdivo (nivolumab) is included in the Pan-Asian Guidelines Adaptation (PAGA) as a second-line therapy for patients with advanced or metastatic colorectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) who progressed on first-line chemotherapy (PMID: 37236086; ESMO.org). | detail... 37236086 |
| MSH6 negative | vaginal carcinoma | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in guidelines as preferred second-line or subsequent therapy for patients with recurrent or metastatic vaginal squamous cell carcinoma or adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org). | detail... |
| MSH6 negative | gastrointestinal system cancer | predicted - sensitive | PD-L1/PD-1 antibody | unspecified immune checkpoint inhibitor | Clinical Study | Actionable | In a retrospective analysis, first-line treatment with immune checkpoint inhibitors (n=30) improved overall response rate (60.7% vs 26.3%; p=0.0005), 24-month progression-free survival (PFS) rate (71.2% vs 7.9%), and median PFS (5.5 months vs not reached; HR=0.21, p<0.0001) compared to first-line chemotherapy (n=103) in patients with mismatch repair-deficient (dMMR) and/or microsatellite instability-high (MSI-H) non-colorectal digestive tract cancers, including pancreatic cancer (PMID: 38537314). | 38537314 |
| MSH6 negative | ovarian carcinoma | predicted - sensitive | PD-L1/PD-1 antibody | Nivolumab | Phase II | Actionable | In a Phase II trial, Opdivo (nivolumab) treatment resulted in an objective response rate of 58.8% (20/34, 7 complete and 13 partial responses) and a progression-free survival rate at 24 mo of 64.7% in patients with MSI-high or deficient mismatch repair (dMMR defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) ovarian or endometrial carcinoma, including responses in 2 patients with uterine clear cell carcinoma and 1 patient with ovarian clear cell carcinoma (PMID: 38653864; NCT03241745). | 38653864 |
| MSH6 negative | endometrial carcinoma | sensitive | PD-L1/PD-1 antibody | Nivolumab | Phase II | Actionable | In a Phase II trial, Opdivo (nivolumab) treatment resulted in an objective response rate of 58.8% (20/34, 7 complete and 13 partial responses) and a progression-free survival rate at 24 mo of 64.7% in patients with MSI-high or deficient mismatch repair (dMMR defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) ovarian or endometrial carcinoma, including responses in 2 patients with uterine clear cell carcinoma and 1 patient with ovarian clear cell carcinoma (PMID: 38653864; NCT03241745). | 38653864 |
| MSH6 negative | endometrial cancer | sensitive | PD-L1/PD-1 antibody | Carboplatin + Durvalumab + Paclitaxel | FDA approved | Actionable | In a Phase III trial (DUO-E) that supported FDA approval, Imfinzi (durvalumab) plus carboplatin and paclitaxel followed by Imfinzi (durvalumab) maintenance improved progression-free survival (PFS) compared to platinum therapy + placebo and placebo maintenance (HR 0.71, p<0.003) in patients with advanced endometrial cancer, with significant PFS benefit (not reached vs 7.0 mo, HR 0.42) observed in the dMMR (as determined by the loss of MLH1, PMS2, MSH2, and MSH6 by IHC) group (PMID: 37864337; NCT04269200). | detail... 37864337 |
| MSH6 negative | prostate adenocarcinoma | predicted - sensitive | Ipilimumab + Nivolumab PD-L1/PD-1 antibody | Ipilimumab + Nivolumab | Case Reports/Case Series | Actionable | In a Phase II trial (INSPIRE), treatment with Yervoy (ipilimumab) and Opdivo (nivolumab) in patients with metastatic prostate adenocarcinoma resulted in a disease control rate (DCR) at 6 mo of 38%, objective response rate (ORR) of 38% (14/37), and median progression-free survival (mPFS) of 4.0 mo in the overall efficacy cohort, and a DCR at 6 mo of 81%, ORR of 75% (9/12, all partial responses), and mPFS or 32.7 mo in patients with mismatch repair deficiency (dMMR) (PMID: 39293514). | 39293514 |
| MSH6 negative | biliary tract cancer | sensitive | PD-L1/PD-1 antibody | Pembrolizumab | Guideline | Actionable | Keytruda (pembrolizumab) is included in the Pan-Asian Guidelines Adaptation (PAGA) for patients with mismatch repair-deficient (dMMR, defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) biliary tract cancer who have progressed on or are intolerant of non-immune checkpoint inhibitor therapies (PMID: 39232586; ESMO.org). | detail... 39232586 |