Dostarlimab,a programmed death receptor-1(PD-1)-blocking IgG4 humanized monoclonal antibody,gained accelerated approval from the US Food and Drug Administration(FDA)in April 2021,and received a full approval in Februa...Dostarlimab,a programmed death receptor-1(PD-1)-blocking IgG4 humanized monoclonal antibody,gained accelerated approval from the US Food and Drug Administration(FDA)in April 2021,and received a full approval in February 2023.Dostarlimab was approved for treating adult patients with mismatch repair deficient(dMMR)recurrent or advanced endometrial cancer(EC)that progressed during or after prior treatment who have no other suitable treatment options.Herein,we review the structure-based mechanism of action of dostarlimab and the results of a clinical study(GARNET;NCT02715284)to comprehensively clarify the efficacy and toxicity of the drug.The efficacy and safety of dostarlimab as monotherapy was assessed in a non-randomized,multicenter,open-label,multi-cohort trial that included 209 patients with dMMR recurrent or advanced solid tumors after receiving systemic therapy.Patients received 500 mg of dostarlimab intravenously every three weeks until they were given four doses.Then,patients received 1000 mg dostarlimab intravenously every six weeks until disease progression or unacceptable toxicity.The overall response rate,as determined by shrinkage in tumor size,was 41.6%(95%confidence interval[CI];34.9,48.6),with 34.7 months as the median response duration.In conclusion,dostarlimab is an immunotherapy-based drug that has shown promising results in adult patients with recurrent or advanced dMMR EC.However,its efficacy in other cancer subtypes,the development of resistance to monotherapy,and efficacy and safety in combination with other immunotherapeutic drugs have not yet been studied.展开更多
Lynch syndrome is the fourth most common cancer in the United States, with an early age of onset and poor prognosis. Here, we present a unique case of a patient with progressive colon cancer due to a late diagnosis of...Lynch syndrome is the fourth most common cancer in the United States, with an early age of onset and poor prognosis. Here, we present a unique case of a patient with progressive colon cancer due to a late diagnosis of Lynch syndrome showing excellent response to immunotherapy. A 59-year-old male with a history of rectal cancer 30 years ago came to the hospital due to a fever and further found a large necrotic colon mass. Biopsy was positive for colorectal cancer;however, due to the size of the tumor, the patient was deemed not a surgical candidate and offered hospice with palliative chemotherapy. Based on further workup, the patient was diagnosed with Lynch syndrome, with colon cancer determined to be responsive to Immunotherapy. He was started on JEMPERLI (Dosterlimab-gxly), and after three cycles of therapy, imaging and PET scan were repeated, showing decreased activity and extent of the tumor—a tremendous success.展开更多
文摘Dostarlimab,a programmed death receptor-1(PD-1)-blocking IgG4 humanized monoclonal antibody,gained accelerated approval from the US Food and Drug Administration(FDA)in April 2021,and received a full approval in February 2023.Dostarlimab was approved for treating adult patients with mismatch repair deficient(dMMR)recurrent or advanced endometrial cancer(EC)that progressed during or after prior treatment who have no other suitable treatment options.Herein,we review the structure-based mechanism of action of dostarlimab and the results of a clinical study(GARNET;NCT02715284)to comprehensively clarify the efficacy and toxicity of the drug.The efficacy and safety of dostarlimab as monotherapy was assessed in a non-randomized,multicenter,open-label,multi-cohort trial that included 209 patients with dMMR recurrent or advanced solid tumors after receiving systemic therapy.Patients received 500 mg of dostarlimab intravenously every three weeks until they were given four doses.Then,patients received 1000 mg dostarlimab intravenously every six weeks until disease progression or unacceptable toxicity.The overall response rate,as determined by shrinkage in tumor size,was 41.6%(95%confidence interval[CI];34.9,48.6),with 34.7 months as the median response duration.In conclusion,dostarlimab is an immunotherapy-based drug that has shown promising results in adult patients with recurrent or advanced dMMR EC.However,its efficacy in other cancer subtypes,the development of resistance to monotherapy,and efficacy and safety in combination with other immunotherapeutic drugs have not yet been studied.
文摘Lynch syndrome is the fourth most common cancer in the United States, with an early age of onset and poor prognosis. Here, we present a unique case of a patient with progressive colon cancer due to a late diagnosis of Lynch syndrome showing excellent response to immunotherapy. A 59-year-old male with a history of rectal cancer 30 years ago came to the hospital due to a fever and further found a large necrotic colon mass. Biopsy was positive for colorectal cancer;however, due to the size of the tumor, the patient was deemed not a surgical candidate and offered hospice with palliative chemotherapy. Based on further workup, the patient was diagnosed with Lynch syndrome, with colon cancer determined to be responsive to Immunotherapy. He was started on JEMPERLI (Dosterlimab-gxly), and after three cycles of therapy, imaging and PET scan were repeated, showing decreased activity and extent of the tumor—a tremendous success.
