SELIMETRY: resensitising iodine refractory differentiated thyroid cancer to radioiodine
Session type: E-poster/poster
Radioiodine refractory differentiated thyroid cancer (RRDTC) carries a poor prognosis. Multi-targeted kinase inhibitors (MKIs) can extend progression free survival (PFS) but are associated with significant toxicity. A pilot study demonstrated that a MEK inhibitor, Selumetinib, can reinstate iodine uptake in RRDTC, potentially making further radioiodine therapy of value. SELIMETRY aimed to replicate these findings, to investigate the degree of clinical benefit in terms of PFS and toxicity with this approach, and to investigate the accuracy of pre-therapy dosimetry.
Patients with RRDTC with evidence of progression by RECIST v1.1 criteria within the previous 12 months but no prior therapy for RRDTC were recruited to this multicentre, single arm phase 2 trial. Eligible patients were given Selumetinib 75mg bd for 4 weeks. Pre- and post- treatment [123I]NaI SPECT/CT scans were assessed centrally for evidence of sufficient increase in iodine uptake to warrant further [131I]NaI therapy. Those with sufficient uptake received 5.5GBq [131I]NaI and had post therapy SPECT/CT scans to allow dosimetric calculations. The primary endpoint was 12 month PFS in the iodine-uptake cohort. It was planned to recruit 60 patients. Assuming an iodine-uptake rate of 60% and a 10% drop out rate this would yield 38 patients in the iodine-uptake cohort.
Due to a lower than expected rate of conversion to iodine uptake, and to slow accrual, it was not considered feasible to recruit sufficient patients to meet the primary endpoint. 30 patients were recruited. 28 received at least one dose of Selumetinib. Nine went on to receive radioiodine therapy. In this group, PFS at 12 months was 62.82% (80% CI: 39.79, 81.54) and median PFS time was 12.13 months. Toxicity was greater than previously reported with Selumetinib. A high degree of correlation between predicted and delivered absorbed dose from post-Selumetinib [123I]NaI SPECT/CT and post [131I]NaI SPECT/CT was demonstrated.
Increased iodine uptake was seen in a proportion of patients following Selumetinib, albeit in fewer patients than previously observed. We have demonstrated that it is possible to predict the absorbed dose delivered at therapy from pre-therapy [123I]NaI imaging.
This study introduces the potential for personalised treatment planning for molecular radiotherapy based on dosimetry.