Clinical Scorecard: Evaluation of Sapanisertib in Patients with Advanced Anaplastic and Radioiodine-Refractory Differentiated Thyroid Cancer: A Phase I/II Study
Inhibition of mTOR complexes 1 and 2 (mTORC1/2) by sapanisertib, targeting PI3K/AKT/mTOR pathway involved in tumor growth and survival
Target Population
Patients with metastatic or recurrent incurable ATC and RAIR DTC refractory to multikinase inhibitors
Care Setting
Multicenter clinical trial setting including phase I safety run-in and phase II nonrandomized trial
Key Highlights
Sapanisertib showed limited clinical efficacy with 11% of ATC patients progression-free at 4 months and 4.5% partial response rate in RAIR DTC.
Median progression-free survival was 1.6 months for ATC and 7.8 months for RAIR DTC patients.
Grade 3 treatment-related adverse events occurred in 30% of patients, including anorexia, nausea, diarrhea, fatigue, skin rash, and hyperglycemia.
Guideline-Based Recommendations
Diagnosis
Diagnosis of ATC and RAIR DTC should include molecular profiling for PI3K/AKT/mTOR pathway alterations, although these were not predictive of response to sapanisertib.
Management
Sapanisertib monotherapy is not recommended as a standard treatment for ATC due to lack of clinically meaningful activity.
Consider approved therapies such as dabrafenib and trametinib for BRAF V600E mutant ATC.
Alternative therapeutic strategies and clinical trials are needed for BRAF wild-type ATC and RAIR DTC refractory to TKIs.
Monitoring & Follow-up
Monitor patients for treatment-related adverse events including gastrointestinal symptoms, fatigue, skin rash, and hyperglycemia during mTOR inhibitor therapy.
Risks
Potential for grade 3 adverse events affecting appetite, gastrointestinal tract, skin, and glucose metabolism.
Limited efficacy in ATC with early trial termination due to futility.
Patient & Prescribing Data
Patients with advanced ATC and RAIR DTC refractory to standard therapies
Sapanisertib at 5 mg daily showed limited efficacy and a manageable safety profile but did not meet primary efficacy endpoints in ATC.
Clinical Best Practices
Use molecular profiling to guide targeted therapy decisions in thyroid cancer.
Employ approved targeted therapies for BRAF-mutated ATC where applicable.
Enroll patients in clinical trials exploring novel agents or combinations for refractory thyroid cancers.
Closely monitor and manage adverse events related to mTOR inhibition to maintain patient quality of life.
by Kartik Sehgal, Anthony Serritella, Mofei Liu, Anne ONeill, Chaitali Nangia, Theodora Pappa, Michael J Demeure, Francis P Worden, Robert I Haddad, Jochen Lorch
