Gemma Eminowicz

Quality-adjusted time without symptoms of disease progression or toxicity of treatment in patients with primary advanced or recurrent endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel

In part 1 of the phase 3 RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer, dostarlimab plus carboplatin-paclitaxel significantly improved progression-free and overall survival vs placebo plus carboplatin-paclitaxel. Post hoc analyses examined the impact of adding dostarlimab to chemotherapy, compared with placebo plus chemotherapy, on quality-adjusted time without symptoms of disease progression or toxicity of treatment in this patient population. Patients were randomized 1:1 to receive dostarlimab/placebo plus chemotherapy every 3 weeks for 6 cycles, followed by dostarlimab/placebo monotherapy every 6 weeks for up to 3 years. Data from the first interim analysis (September 28, 2022) were used, and quality of life (QoL) was assessed with the EuroQoL 5-Dimensions 5-Level questionnaire. Quality-adjusted time without symptoms of disease progression or toxicity of treatment was calculated as the sum product of the restricted mean survival times spent in 3 mutually exclusive states: toxicity, time without symptoms of disease progression or treatment toxicity, and relapse, and utilized each state's corresponding QoL. In the dostarlimab and placebo arms, 241 and 246 patients were analyzed for safety, respectively. In the overall population, the mean (95% CI) duration of quality-adjusted time without symptoms of disease progression or toxicity of treatment was significantly longer in the dostarlimab arm (24.75 months [22.88 to 26.65 months]) than in the placebo arm (20.34 months [18.95 to 21.76 months]; the mean difference [95% CI] of 4.41 months [2.01 to 6.77 months], p < .001). Benefits in quality-adjusted time without symptoms of disease progression or toxicity of treatment after dostarlimab treatment were observed regardless of mismatch repair/microsatellite instability status or toxicity criteria used and were predominantly driven by the time without symptoms of disease. Dostarlimab plus carboplatin-paclitaxel treatment is associated with meaningful improvement in survival, avoidance of substantial toxicity, and maintenance of patient-reported QoL in patients with primary advanced or recurrent endometrial cancer.

Optimizing adjuvant treatment strategy in advanced clear cell endometrial cancer: systematic review and meta-analysis.

Clear cell endometrial cancer is a rare, aggressive sub-type with a poor prognosis. Due to its low incidence, treatment strategies are often extrapolated from other high-risk histologies. Optimal adjuvant treatment following primary surgery for advanced clear cell endometrial cancer is unclear. This meta-analysis compares radiotherapy-containing strategies with chemotherapy alone in the adjuvant setting. We conducted a systematic literature review (Medline, Cochrane CENTRAL, Embase, and Web of Science) of studies evaluating first-line adjuvant treatment for advanced clear cell endometrial cancer. Inclusion criteria were: English language; full peer-reviewed manuscript; International Federation of Gynecology and Obstetrics 2009 stage III/IV clear cell patients receiving adjuvant chemotherapy and/or radiotherapy after primary surgery (staging or cytoreductive); and overall survival data specific to this cohort. Studies reporting overall survival estimates comparing treatment groups in advanced clear cell endometrial cancer patients were included. A random-effects model was used to estimate the overall survival hazard ratio (HR) and 95% confidence interval (CI), pooled using the generic inverse-variance method with adjusted weights. The search yielded 5421 results, of which 6 met the inclusion criteria. 1 article included 2 independent cohorts, resulting in 7 studies included in the meta-analysis. A total of 1266 patients received adjuvant chemotherapy alone, and 531 patients received adjuvant chemoradiotherapy or radiotherapy only. The pooled HR from 7 studies was 0.63 (95% CI 0.53 to 0.74), corresponding to a 37% reduction in the risk of death for patients receiving adjuvant chemoradiotherapy or radiotherapy compared with chemotherapy alone. The results were consistent across the studies, with no evidence of heterogeneity (p =.89). Adjuvant chemoradiotherapy or radiotherapy was associated with improved overall survival in advanced clear cell endometrial cancer compared with chemotherapy alone. These findings support prospective validation and define the optimal integration of radiotherapy in this setting.