Gynecological Cancers: Treatment Updates and Expert Perspectives - Episode 12
Panelists discuss how the RUBY trial’s real-world data confirms the efficacy of dostarlimab maintenance therapy and surprisingly shows improved quality of life outcomes with delayed time to deterioration compared to placebo, providing confidence in using immunotherapy maintenance despite potential adverse effects.
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This segment focuses on selinexor, an XPO1 inhibitor that has shown remarkable efficacy in endometrial cancer treatment. The discussion highlights the surprising and impressive results from the SIENDO trial, which demonstrated significant progression-free survival improvements across molecular subtypes, with particularly striking benefits in mismatch repair–proficient patients (5 months versus 40 months). The dramatic efficacy differences between MMR-deficient and MMR-proficient patients suggest important biological mechanisms that may inform future treatment strategies and patient selection criteria.
The conversation explores the scientific rationale behind selinexor’s mechanism of action, particularly its role in preventing nuclear export of tumor suppressor proteins like p53. Experts explain how this mechanism may be most relevant in p53 wild-type tumors, where functional p53 can still contribute to tumor suppression, while p53-mutated tumors may be less responsive due to their addiction to alternative survival pathways. This biological understanding supports the ongoing XPORT trial, which aims to prospectively validate biomarker-driven treatment selection.
Quality of life considerations emerge as a crucial aspect of treatment decision-making, with recent data from the RUBY trial showing that patients receiving dostarlimab maintenance experienced improved quality-of-life outcomes compared to placebo. The discussion reveals that immunotherapy maintenance led to delayed deterioration, improved global functioning, and decreased pain, likely due to effective disease control and prevention of cancer recurrence. These findings provide reassurance to clinicians concerned about toxicity-related quality of life impacts from maintenance immunotherapy.