Selinexor
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Selinexor: From an Unspecified Original Indication to Drug-Induced Osteoporosis
One-Sentence Summary
Selinexor is an oral XPO1 (exportin 1) inhibitor marketed in Singapore as XPOVIO, but the registered indication text is not available in the data compiled for this report. The TxGNN model's top-ranked prediction is drug-induced osteoporosis, which has no clinical trials and no publications behind it, so it is a computational prediction only. Among the 10 predictions, the one with the most clinical grounding is squamous cell lung carcinoma, with 2 selinexor trials (one withdrawn and one terminated), neither of which produced usable efficacy evidence.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available (the Singapore registration lists no indication text) |
| Predicted New Indication | Drug-induced osteoporosis |
| TxGNN Prediction Score | 99.22% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the compiled data. Selinexor is known to be an XPO1 inhibitor that blocks nuclear export, causing tumour suppressor proteins to be retained in the nucleus of cancer cells. This is an anticancer mechanism.
For drug-induced osteoporosis, the supplied data supports no plausible link to bone metabolism. The drug's known adverse effects (nausea, anorexia, weight loss) also give no rationale for benefit in this setting. The high score (0.992) reflects a model output only, and the prediction should be treated with caution.
Other predictions are somewhat more plausible mechanistically, because they are cancers:
- Squamous cell lung carcinoma has the most clinical grounding, with two selinexor trials registered in lung cancer settings.
- Breast cancer subtypes (HER2-positive, progesterone-receptor positive or negative, luminal A or B, normal breast-like) are supported only indirectly. The linked literature concerns selinexor and XPO1 inhibition in myeloma, lymphoma and other diseases, with no breast cancer-specific data.
- Gestational trophoblastic neoplasm, cervical neuroblastoma and schwannoma of jugular foramen are prediction-only, with no supporting data.
Clinical Trial Evidence
The top-ranked prediction (drug-induced osteoporosis) has no registered clinical trials. The table below shows trials for the best-supported alternative prediction, squamous cell lung carcinoma.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02536495 | Phase 1/2 | Withdrawn | 0 | Selinexor plus docetaxel as second-line therapy in relapsed squamous cell lung cancer; no data generated |
| NCT02213133 | Phase 2 | Terminated | 45 | Open-label, single-arm selinexor study in squamous cell carcinoma of the head and neck, lung or oesophagus; early termination limits interpretability, and lung histology specificity is unconfirmed |
Literature Evidence
The top-ranked prediction (drug-induced osteoporosis) has no linked literature. The table below shows selected publications from other predictions.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32589977 | 2020 | Phase 2 single-arm trial | Lancet Haematology | SADAL: single-agent selinexor in relapsed or refractory DLBCL (not breast cancer) |
| 34132444 | 2021 | Review | Oncologist | FDA approval summary of selinexor for relapsed or refractory DLBCL |
| 35880450 | 2022 | Review | Curr Opin Oncol | Clinical development of selinexor in multiple myeloma and non-Hodgkin lymphomas |
| 32574233 | 2020 | Review | Front Pharmacol | Small-molecule CRM1 (XPO1) inhibitors and their potential in cancer |
| 27113410 | 2016 | Review | Pharmacol Ther | Importins and exportins as therapeutic targets in cancer |
| 30826604 | 2019 | Review | Curr Opin Cell Biol | Inhibitors of nuclear transport |
| 32569833 | 2020 | Review | Drug Discov Today | Exportin 1 inhibition as antiviral therapy |
| 34926302 | 2021 | Preclinical | Front Oncol | Selinexor enhances NK cell activation against malignant B cells |
| 36943683 | 2023 | Review | Curr Opin Obstet Gynecol | Endometrial cancer molecular subtypes (not directly relevant to HER2-positive breast cancer) |
| 38288815 | 2024 | Review | Anticancer Agents Med Chem | Synthetic chemistry of FDA-approved anticancer drugs (no clinical evidence) |
None of these publications provides breast cancer-specific or bone-related evidence for selinexor.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN16434P | XPOVIO Film-Coated Tablets 20mg | Film-coated tablet (oral) | Not specified in the available data |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (XPO1 / nuclear export inhibitor); formal classification should be confirmed against the package insert |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Nausea and anorexia are known adverse effects; please refer to the package insert for the formal classification |
| Monitoring Items | Please refer to the package insert; routine monitoring of blood counts and liver and renal function is generally advisable for anticancer agents |
| Handling Protection | Please refer to the package insert and local cytotoxic drug handling regulations |
Safety Considerations
- Drug Interactions: The interaction screening found 81 interacting drugs. Examples of Major interactions include deferiprone, samarium (153Sm) lexidronam, adalimumab, baricitinib, certolizumab pegol, cladribine and clozapine. Examples of Moderate interactions include strontium chloride Sr-89, roflumilast, chloramphenicol, zidovudine, azathioprine, anakinra, alemtuzumab and several vaccines (including tetanus toxoid, anthrax and live cholera vaccines). Many of these involve myelosuppressive or immunosuppressive agents.
Warnings and contraindications from the package insert were not available. Please refer to the package insert for this information.
Conclusion and Next Steps
Decision: Hold
Rationale: The top prediction, drug-induced osteoporosis, rests on a model score alone (L5), with no trials, no literature, and no plausible mechanistic link to bone metabolism. The other nine predictions are also at L4 or L5, and none has completed trials showing benefit.
To proceed, the following is needed:
- The HSA package insert (approved indications, warnings, contraindications), which is currently a blocking gap for safety screening
- Detailed mechanism of action data from DrugBank
- For squamous cell lung carcinoma, the termination reasons and any posted results of NCT02213133, and confirmation of whether squamous lung histology was enrolled
- A mechanistic or preclinical rationale linking XPO1 inhibition to bone metabolism before any further work on drug-induced osteoporosis
- Breast cancer-specific preclinical or clinical data if the breast cancer subtype predictions are to be pursued
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.