Karyopharm Updates on SIENDO Study for Advanced TP53 Wild-Type Endometrial Cancer at 2024 ASCO Plenary

Karyopharm Therapeutics Inc., a pharmaceutical company known for pioneering cancer therapies, presented encouraging data on the effectiveness of selinexor in the maintenance treatment of advanced or recurrent TP53 wild-type endometrial cancer. The findings were shared at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, highlighting significant improvements in progression-free survival (PFS) and quality of life metrics.

Key Findings from the SIENDO Study

The SIENDO study, a Phase 3 trial, explored selinexor's potential as a maintenance therapy following initial treatment with platinum-based chemotherapy. The primary analysis indicated that selinexor did not show clinically meaningful improvements in median PFS for the overall intent-to-treat (ITT) population. However, a pre-specified exploratory subgroup analysis of patients with TP53 wild-type endometrial cancer revealed promising results.

In this subgroup of 113 patients, those treated with selinexor experienced a median PFS of 28.4 months compared to just 5.2 months for the placebo group. Further analysis showed that patients with proficient mismatched repair status (pMMR) and TP53 wild-type tumors had a median PFS of 39.5 months on selinexor, versus 4.9 months with the placebo. These findings suggest that selinexor could be a highly effective maintenance therapy for this specific patient subgroup.

Quality-Adjusted Time Without Symptoms or Toxicity (Q-TWiST)

An important aspect of cancer treatment is balancing efficacy with the quality of life. The Q-TWiST metric, which assesses both the duration of survival without symptoms or toxicity and the quality of that survival, showed substantial improvement for patients on selinexor. The restricted mean Q-TWiST was 26 months for selinexor-treated patients, compared to 15 months for those on placebo, indicating an 11-month advantage.

Dr. Reshma Rangwala, Chief Medical Officer at Karyopharm, emphasized that these findings, particularly the nearly 40 months median PFS for patients with TP53 wild-type and pMMR tumors, suggest selinexor's potential as an optimal maintenance therapy for endometrial cancer. The ongoing Phase 3 trial aims to confirm these benefits and potentially establish a new standard of care for this patient subgroup.

Safety Profile

As of the April 2024 data cutoff, no new safety concerns were identified. The most common side effects in selinexor-treated patients included nausea, vomiting, and diarrhea, primarily of grades 1-2. More severe (grade 3-4) events were less frequent but included neutropenia, nausea, and thrombocytopenia. The rate of treatment discontinuation due to adverse events was 17%.

Expert Commentary

Dr. Vicky Makker from Memorial Sloan Kettering Cancer Center highlighted the significance of the emerging data, noting that the long-term follow-up reinforces selinexor's potential benefits for endometrial cancer patients, particularly those with mismatch repair-proficient disease. These findings contribute to the growing evidence supporting selinexor as a viable maintenance treatment for patients with limited options.

Ongoing and Future Research

Selinexor is currently being evaluated in a global Phase 3 study (EC-042) as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer. The study, expected to enroll up to 220 patients, aims to further investigate selinexor's efficacy and safety. Data from this trial are anticipated in the first half of 2025.

Conclusion

The exploratory subgroup analysis from the SIENDO study presents compelling evidence that selinexor may significantly improve progression-free survival and quality of life for patients with TP53 wild-type and pMMR endometrial cancer. As ongoing research continues to validate these findings, selinexor has the potential to emerge as a new standard of care in the maintenance treatment landscape for endometrial cancer.

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