ENGOT-EN5/GOG-3055/SIENDO: Selinexor in Endometrial Cancer (Phase II)
Ignace Vergote
Disease Site: Advanced or Recurrent Endometrial Cancer (EC)
Publication Title: Oral Selinexor as Maintenance Therapy After First-Line Chemotherapy for Advanced or Recurrent Endometrial Cancer
Year of Publication: 2023
Hypothesis: Selinexor inhibits exportin-1, leading to nuclear accumulation of tumor suppressor proteins, potentially improving progression-free survival (PFS) in advanced or recurrent EC patients after first-line chemotherapy.
Inclusion Criteria:
- Patients 18 years or older
- Histologically confirmed EC
- Completed ≥12 weeks of taxane-platinum combination chemotherapy achieving partial or complete response
Exclusion Criteria:
- Sarcomas, small cell carcinoma with neuroendocrine differentiation, clear cell carcinomas
- Previous treatment with an XPO1 inhibitor or anti–PD-1/PD-L1 immunotherapy - Brain metastases
Primary Endpoint: Progression-free survival (PFS)
Experimental Arm(s):
- 80 mg oral selinexor once weekly
- Supportive care: 8 mg ondansetron 2-3 times daily for 1-3 days post-dose, 2.5-5.0 mg olanzapine daily for the first 2 months
Control Arm:
- Placebo with identical supportive care measures
Results:
| Metric | Selinexor | Placebo | P-value | Hazard Ratio (95% CI) |
|---|---|---|---|---|
| Median PFS (months) | 5.7 | 3.8 | .126 | 0.76 (0.54 to 1.08) |
| Median PFS in TP53 wild-type (months) | 13.7 | 3.7 | .002 | 0.41 (0.23 to 0.72) |
| Grade 3 toxicities (%) | Nausea (9), Neutropenia (9), Thrombocytopenia (7) | - | - | - |
Conclusions: Selinexor did not meet the primary endpoint of statistical significance in overall population PFS. Subgroup analysis indicated potential benefit in TP53 wild-type EC patients.
Limitations:
- Small sample size in subgroups
This study suggests potential for selinexor in specific subgroups, although general applicability in EC remains limited by side effects and mixed overall efficacy. Further trials are recommended, particularly focusing on genetically defined subgroups.