Endocrine Abstracts

Noninfectious pneumonitis is a recognised toxicity associated with mTOR inhibitors, such as everolimus. We report a 75 year old female with histologically confirmed on colonoscopy, non-functioning Grade 2 (Ki 9%) in situ terminal ileal NET with ileocolic lymphadenopathy and multiple liver metastases, who was commencedon somatostatin analogue therapy at presentation in May 2017, but developed progressive disease on CT by February 2018. Based on RADIANT – 4 which showed an improved progression – free survival, therapy was started with everolimus at 50% dose modification (5mg orally) due to the risk of potentiation with concomitant verapamil, a moderate CYP3A4 inhibitor, but which is not considered a contraindication. The patient was admitted 3 weeks after starting treatment, initially with mucositis and diarrhoea: everolimus was stopped, and CXR was clear. Within 5 days, the patient developed fever, dry cough and rapidly progressive, life – threatening dyspnoea requiring HDU outreach support. CTPA showed marked ground glass opacification in all lobes with new pleural effusions. IV antibiotics, including septrin to cover PCP, were commenced, and high dose iv methylprednisolone. The patient improved rapidly and was subsequently discharged home. Repeat CT scan performed 2 months later showed complete resolution of pneumonitis, and, surprisingly after such a short course of therapy, some improvement in liver metastases. In RADIANT-4, noninfectious pneumonitis was reported in 16% of patients, with only 1% being grade 3, and no grade 4 cases; similarly in RADIANT-3, all grades was 16%, but 5 patients (2.5%) had grade 3/4. Interestingly, although experience in NETS is limited, in patients with metastatic renal cell carcinoma where everolimus has been widely used, CT – verified pneumonitis was 34%, and was associated with longer progression – free and overall survival. Whilst the SPC of everolimus advises monitoring for ‘clinical symptoms or radiological changes; fatal cases have occurred’, we believe that the incidence of noninfectious pneumonitis may be under reported in patients with advanced grade 1/2 NETS, and that serial imaging with CT surveillance rather than CXR, and early recognition of mild or even asymptomatic cases, may prevent life threatening complications.