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Fluctuating obliterative bronchiolitis in RET-mutant medullary thyroid cancer patient treated with selpercatinib
Carla Gambale1, Alessandro Prete1, Chiara Romei2
1Department of Clinical and Experimental Medicine, Unit of Endocrinology, Pisa University Hospital, Pisa, Italy.
Abstract:
Highly selective RET inhibitor selpercatinib has demonstrated notable efficacy in advanced/progressive RET-mutant medullary thyroid cancer (MTC) patients. However, despite a more tolerable toxicity profile than multikinase inhibitors, peculiar adverse events (AEs) have been described. Obliterative bronchiolitis (OB) is a respiratory disease characterized by inflammation and fibrosis in small conducting airways. We evaluated a 70-year-old man with advanced RET-mutant MTC who developed OB during treatment with selpercatinib. Radiological features of OB occurred early and persisted during selpercatinib treatment, with a waxing and waning pattern. Notably, a partial response of MTC was achieved during the treatment, and selpercatinib was never reduced or interrupted. The almost complete absence of symptoms and the fluctuating trend, without specific treatment for OB, suggested that it is necessary to carefully evaluate the risks mediated by this AE with the risks of modifying or discontinuing the anti-cancer therapy.
Insights
Selpercatinib shows efficacy in advanced medullary thyroid cancer (MTC). However, this RET inhibitor can cause obliterative bronchiolitis (OB), a lung condition that requires careful risk-benefit assessment during treatment.
Area of Science:
- Oncology
- Pulmonology
- Pharmacology
Background:
- Selpercatinib is a highly selective RET inhibitor effective for advanced RET-mutant medullary thyroid cancer (MTC).
- While generally well-tolerated, selpercatinib can cause unique adverse events (AEs), including respiratory complications.
Observation:
- A 70-year-old male patient with advanced RET-mutant MTC developed obliterative bronchiolitis (OB) during selpercatinib treatment.
- Radiological signs of OB appeared early, persisted with fluctuating severity, and occurred alongside a partial MTC response without treatment modification.
Findings:
- The patient experienced minimal symptoms despite persistent radiological findings of OB.
- The fluctuating nature of OB and the sustained anti-cancer response suggest a complex interplay between the drug, the AE, and the underlying malignancy.
Implications:
- This case highlights the need for careful consideration of the risks associated with selpercatinib-induced OB versus the benefits of continuing anti-cancer therapy.
- Further research is warranted to understand the pathogenesis and management of OB in patients treated with RET inhibitors.
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