Dostarlimab plus chemotherapy has recently been designated as the standard-of-care treatment for primary advanced and recurrent endometrial cancer. This promising combination therapy has shown significant improvement in progression-free survival and overall response rates in clinical trials, offering new hope to patients with this aggressive form of cancer. In this article, we will delve into the details of this breakthrough treatment, exploring its mechanism of action, safety profile, and the latest research findings that support its use as a new treatment option for endometrial cancer.
A new standard of care has been set for patients with primary advanced or recurrent endometrial cancer, following the positive results from the phase 3 RUBY trial. Dostarlimab (Jemperli) combined with chemotherapy has demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with an early trend toward overall survival (OS). At median follow-up of 25.38 months, the estimated 12-month PFS rate observed with dostarlimab plus carboplatin and paclitaxel was 48.2% compared with 29.0% in the placebo/chemotherapy arm, in the overall population. At 24 months, the PFS rate was estimated to be 36.1% with dostarlimab and chemotherapy vs 18.2 % with placebo and chemotherapy. The hazard ratio for the difference between treatment arms was 0.64.
Carboplatin plus paclitaxel is the golden standard for primary advanced or recurrent endometrial cancer but the long-term median OS shown with this treatment is under 3 years. Investigators hypothesized that adding an agent like dostarlimab to chemotherapy can help address the need for advances in first-line endometrial cancer. Dostarlimab, an immune checkpoint inhibitor, has previously shown durable activity in patients with previously treated, mismatch repair deficient (dMMR) and microsatellite instable (MSI) endometrial cancer, as well as those with MMR profient (MMRp) and microsatellite stable (MSS) disease. The dMMR/MSI-high endometrial cancer population, specifically, has a higher response to anti-PD-1 therapy. When combined with chemotherapy, dostarlimab was hypothesized to help with immunogenic cell death, lower immunosuppression in the tumor microenvironment, and demonstrated clinical activity.
In the study, 494 patients with primary advanced or recurrent endometrial cancer were randomized to receive either primary advanced or recurrent endometrial cancer intravenous (IV) dostarlimab with carboplatin and paclitaxel or matching placebo with carboplatin and paclitaxel. Of the 494 patients randomized, 53 patients (21.6%) in the dostarlimab arm and 65 patients (26.1%) in the placebo arm had dMMR/MSI-high tumors. Also, in the dostarlimab arm, 192 patients (78.4%) had MMRp/MSS tumors, as did 184 patients (73.9%) in the placebo arm. Most patients in both arms did not have prior external pelvic radiation. In terms of disease status, the majority of patients had recurrent disease.
In the overall population, OS had reached 33% maturity at the time of the analysis. The estimated 12-month OS in the dostarlimab/chemotherapy arm was 84.6% compared with 81.3% with placebo/chemotherapy. At 24-months, the estimated OS was 71.3% in the dostarlimab/chemotherapy arm vs 56.0% in the placebo/chemotherapy arm.
Moreover, PROs data show that adding dostarlimab to carboplatin/paclitaxel did not negatively impact the quality-of-life of patients. Any-grade treatment-emergent adverse events (TEAE) occurred in all patients during the study. Grade 3 or higher TEAEs occurred in 70.5% of the dostarlimab/chemotherapy arm compared with 59.8% of the placebo/chemotherapy arm, and serious TEAEs were observed in 37.8% vs 27.6%, respectively. Any-grade treatment-related, immune-related AEs were seen in 38.2% of the dostarlimab arm vs 15.4% of the placebo arm. AEs resulted in discontinuation of dostarlimab or placebo in 17.4% of the dostarlimab arm vs 9.3% of the placebo arm. Treatment discontinuation resulting from a TEAE occurred in 10.0% of patients in the dostarlimab arm vs 7.7% and 9.3%, respectively, in the placebo arm. TEAEs led to death in 2.1% of patients treated with dostarlimab vs no patients in the placebo arm.
In conclusion, dostarlimab plus carboplatin/paclitaxel represents a new standard of care for patients with primary advanced or recurrent endometrial cancer, achieving a statistically significant and clinically meaningful improvement in progression-free survival (PFS) and overall survival (OS), with a manageable safety profile.
In conclusion, Dostarlimab Plus Chemo has been designated as a standard of care for primary advanced/recurrent endometrial cancer. The results of clinical trials have demonstrated its efficacy and safety in improving progression-free survival and overall survival rates in patients. As medical technology continues to advance, we can hope for further innovations in cancer treatment that will improve the lives of patients and their families. The approval of Dostarlimab Plus Chemo marks a significant milestone in the fight against endometrial cancer and provides hope for a brighter future.
