Corticosteroids for Managing TRK Inhibitor Withdrawal Pain: A Report on Two Cases

Background: Neurotrophin receptor tyrosine kinase (NTRK) fusions are potent oncogenic mutations. Inhibitors such as larotrectinib, entrectinib and repotrectinib are used when cancer cells harbor NTRK1, NTRK2 or NTRK3 fusion. Signal disruption between nerve growth factor (NGF) and its target is thought to impact nociception. Withdrawal pain is reported with larotrectinib and entrectinib. Case presentation: Two male patients aged 37 and 41 years old and treated with, respectively, repotrectinib and larotrectinib for NTRK fusion-positive solid tumors experienced debilitating pain after abrupt cessation of their targeted therapy. Short courses of prednisone for the former and dexamethasone for the latter were initiated after failure of standard analgesia. Both patients improved within 24 h and the pain did not recur after steroids were weaned off. They had improvements in their functional status without unexpected toxicity. Conclusions and relevance: For patients experiencing TRK inhibitor withdrawal pain, especially when tapering down the inhibitor is not an available strategy, a short course of corticosteroids can provide lasting relief. These cases emphasize the importance of better understanding the mechanism underlying the relationship between NRTK, NGF and nociception.