Dostarlimab, a novel immunotherapy for endometrial cancer
|
Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on July 10th, 2023
|
The combination chemotherapy of carboplatin and paclitaxel has been used as the first-line treatment for endometrial cancer, but their long-term outcomes are relatively poor. Dostarlimab is an monoclonal antibody that can target the PD-1 receptors that are highly expressed by certain subset of endometrial tumor cells. Thus, the pharmaceutical company GlaxoSmithKline had sponsored a study to assess the efficacy and safety of dostarlimab as a immunotherapy for endometrial cancer.
The phase 3 clinical trial included 494 participants who had been diagnosed with stage III and IV endometrial cancer using the standards set by the International Federation of Gynecology and Obstetrics. The median age of the study participants was around 64 years old and approximately half was experiencing recurrent disease. Further testing was performed to assess the mismatch repair mechanism of the tumor, and approximately one quarter of the patients has a deficient mechanism (dMMR). Since, PD-1 overexpression is associated with dMMR tumor, a stratified analysis was performed to assess the efficacy of dostarlimab in patients with deficient (dMMR) and proficient mismatch repair mechanisms (pMMR). The participants were randomly assigned to receive 500 mg of dostarlimab or placebo in addition to the standard chemotherapy of carboplatin and paclitaxel. The agents were transfused intravenously in a loading cycle of 3 weeks; after 6 loading cycles, the dose was increased to 1000 mg every 6 weeks, and the treatment was continued for 3 years or until either the disease exacerbated or the patients had to withdraw from the study. After 24 months of treatment, the researchers concluded that dostarlimab reduced the risk of tumor growth or death by 36% in all study participants, when compared to placebo. The effectiveness of dostarlimab was significantly higher in patients with dMMR tumors; the risk of tumor progression or death was reduced by 72%. In terms of safety, the rate of adverse events were similar between the two groups, with alopecia and fatigue being the most commonly reported. Despite the similarity in frequency, the adverse events reported by those treated with dostarlimab were significantly more severe.
The phase 3 clinical trial included 494 participants who had been diagnosed with stage III and IV endometrial cancer using the standards set by the International Federation of Gynecology and Obstetrics. The median age of the study participants was around 64 years old and approximately half was experiencing recurrent disease. Further testing was performed to assess the mismatch repair mechanism of the tumor, and approximately one quarter of the patients has a deficient mechanism (dMMR). Since, PD-1 overexpression is associated with dMMR tumor, a stratified analysis was performed to assess the efficacy of dostarlimab in patients with deficient (dMMR) and proficient mismatch repair mechanisms (pMMR). The participants were randomly assigned to receive 500 mg of dostarlimab or placebo in addition to the standard chemotherapy of carboplatin and paclitaxel. The agents were transfused intravenously in a loading cycle of 3 weeks; after 6 loading cycles, the dose was increased to 1000 mg every 6 weeks, and the treatment was continued for 3 years or until either the disease exacerbated or the patients had to withdraw from the study. After 24 months of treatment, the researchers concluded that dostarlimab reduced the risk of tumor growth or death by 36% in all study participants, when compared to placebo. The effectiveness of dostarlimab was significantly higher in patients with dMMR tumors; the risk of tumor progression or death was reduced by 72%. In terms of safety, the rate of adverse events were similar between the two groups, with alopecia and fatigue being the most commonly reported. Despite the similarity in frequency, the adverse events reported by those treated with dostarlimab were significantly more severe.