Database and Search Strategy for Selpercatinib Comparative Effectiveness Data
Use PubMed with the search terms "Selpercatinib" or "RET inhibitor" limited to Randomized Controlled Trials to find the highest quality comparative effectiveness data for this patient.
Rationale for Database Selection
PubMed is the optimal choice because it provides comprehensive access to peer-reviewed medical literature indexed in MEDLINE, including the pivotal randomized controlled trials that form the basis for selpercatinib's regulatory approvals and clinical guidelines 1, 2.
Why PubMed Over Other Options:
EMBASE limitations: While comprehensive, searching "Retevmo" (brand name only) with "Standard of Care" is too restrictive and will miss critical studies using the generic name selpercatinib 1
Google Scholar problems: Lacks sophisticated medical subject heading (MeSH) indexing, returns excessive non-peer-reviewed content, and the search terms "Selpercatinib" or "Cancer" are far too broad to efficiently identify comparative effectiveness data 1
ScholarOne issues: This is primarily a manuscript submission platform, not a literature search database, making it inappropriate for clinical evidence retrieval 1
Search Strategy Justification
Use of Generic and Class Terms
The search combining "Selpercatinib" OR "RET inhibitor" captures both:
- Studies specifically evaluating selpercatinib by name 1
- Comparative studies of RET inhibitors as a class that include selpercatinib 1
RCT Limiter is Critical
The RCT filter is essential because the most recent high-quality comparative effectiveness data comes from the phase 3 LIBRETTO-531 trial, which directly compared selpercatinib to standard multikinase inhibitors (cabozantinib or vandetanib) 2. This trial demonstrated:
- Superior progression-free survival: not reached vs 16.8 months (HR 0.28, P<0.001) 2
- Superior treatment failure-free survival: not reached vs 13.9 months (HR 0.25, P<0.001) 2
- Higher response rates: 69.4% vs 38.8% 2
- Better tolerability: 4.7% vs 26.8% treatment discontinuation 2
What This Search Will Capture
Primary Evidence You Need:
For RET-mutant medullary thyroid cancer:
- The LIBRETTO-531 phase 3 RCT showing selpercatinib superiority over cabozantinib/vandetanib 2
- The LIBRETTO-001 phase 1/2 trial data: 69% ORR in pretreated patients, 73% ORR in treatment-naïve patients 1
For RET fusion-positive NSCLC:
- LIBRETTO-001 data: 64% ORR in platinum-pretreated patients, 85% ORR in treatment-naïve patients 1
- External control cohort analyses comparing selpercatinib to standard chemotherapy 3
For RET fusion-positive thyroid cancer:
- LIBRETTO-001 data: 79% ORR in pretreated patients, 100% ORR in treatment-naïve patients 1
Safety Data for Hospital Monitoring
This search strategy will also retrieve critical safety information needed for your hospitalized patient 4, 5:
Most Common Adverse Events to Monitor:
- Hepatotoxicity: ALT elevation (30.5% early, 11.8% grade ≥3) - requires liver function monitoring 5
- Hypertension: 19.7% grade ≥3 - blood pressure monitoring essential 5
- QT prolongation: requires ECG monitoring 4
- Hemorrhagic events: monitor for bleeding 4
Acute Delirium Considerations:
The patient's acute delirium could potentially be related to:
- Drug-induced liver injury (reported serious adverse event) 1, 5
- Hyponatremia (9.2% grade ≥3) 5
- Tumor lysis syndrome (listed warning) 4
- Hypersensitivity reactions 4
Comparative Advantage Over Standard Care
The evidence consistently shows selpercatinib outperforms traditional multikinase inhibitors (sorafenib, lenvatinib, cabozantinib, vandetanib) with 1:
- Higher response rates across all RET-altered cancers
- Longer duration of response
- Significantly fewer dose reductions required (38.9% vs 77.3%) 2
- Lower discontinuation rates (4.7% vs 26.8%) 2
- Predominantly grade 1-2 adverse events 1
Traditional MKIs showed limited activity with high toxicity: dose reduction rates of 23-79% and discontinuation rates of 8-21% in lung cancer, with similar patterns in thyroid cancer 1.