A study co-led by UCLA Health Jonsson Comprehensive Cancer Center investigators found that combining the immunotherapy drug dostarlimab with standard chemotherapy not only provides a meaningful improvement in survival for patients with advanced endometrial cancer, but also improves the quality of that extended survival by minimizing the time spent suffering from disease symptoms or severe treatment side effects.
The international team found patients who received the dostarlimab combination treatment gained at least 10% more high quality-adjusted time without symptoms of disease progression or toxicity of treatment, a comprehensive measure that accounts for survival, treatment side effects and patient-reported well-being, compared to those treated with chemotherapy alone. In some cases, this translated to as much as 5.5 additional months of extended, high-quality life.
Notably, the study found that although more patients in the dostarlimab arm experienced serious side effects (grade 3 or higher), the overall benefit of extended, high-quality survival outweighed the risks. Immune-related complications were effectively managed, and most serious side effects occurred early during treatment.
BACKGROUND
Dostarlimab is an anti-PD-1 checkpoint inhibitor, a type of immunotherapy that helps the immune system recognize and attack cancer cells. It was previously shown in the phase 3 clinical trial known as RUBY to improve progression-free and overall survival in patients with advanced or recurrent endometrial cancer. However, these endpoints did not consider patient quality of life.
METHOD
This new analysis of the RUBY trial, which enrolled 494 adults with advanced or recurrent endometrial cancer unlikely to be cured by surgery or radiation, looked beyond how long patients lived and focused on how they felt during that time. Researchers used data from the first interim analysis to evaluate how the treatment affected quality-adjusted time without symptoms or side effects. They calculated this by dividing each patient's time into three states: time with side effects, time without symptoms or side effects, and time after the cancer progressed. Quality of life data was collected through patient questionnaires at multiple timepoints. Statistical methods, including survival analysis and utility scoring, were used to compare the two treatment groups.
IMPACT
The study suggests that dostarlimab plus chemotherapy not only helps patients live longer but preserves the quality of that time, further supporting its use as a new standard of care for advanced or recurrent endometrial cancer.
"This is the first study to demonstrate a statistically significant improvement in both overall survival and quality-adjusted survival with an immunotherapy-chemotherapy combination in this disease setting," said Dr. Dana Chase , a professor of obstetrics and gynecology in the division of gynecologic oncology at the David Geffen School of Medicine at UCLA and first author of the study. "It's a major step forward in the treatment of endometrial cancer."
JOURNAL
The study was published(Link is external) (Link opens in new window) in the International Journal of Gynecological Cancer.
AUTHORS
Dr. Chase is the study's lead and first author. The senior author is Mansoor Raza Mirza from Copenhagen University Hospital. Other authors are Jorn Herrstedt, Eirwen M. Miller, Lucy Gilbert, Oleksandr Zub, Cara Mathews, Roberto Angioli, Michael Teneriello, Martina Gropp-Meier, Matthew A. Powell, Anna K.L. Reyners, Noelle G. Cloven, Gemma Eminowicz, Sarah E. Gill, Beata Maćkowiak-Matejczyk, Bhavana Pothuri, Vanessa Samouëlian, Angela Jain, Jonathan Boone, Sara Bouberhan, Joshua Trinidad, Patricia Braly, Barbara Buttin, Floor J. Backes, Brandon Sawyer, Grace Antony, Jamie Garside, Odette Allonby and Carolyn K. McCourt. A list of affiliations can be found here .
FUNDING
The study was supported by GSK, a British multinational pharmaceutical and biotechnology company.
