Imatinib in advanced GIST: if it's working, don't stop a good thing
Mené sur 58 patients atteints d'une tumeur gastro-intestinale de stade avancé (durée de suivi médiane : 235,2 mois), cet essai multicentrique de phase III compare l'efficacité, du point de vue de la survie sans progression, d'une interruption et d'une continuation du traitement par imatinib
Imatinib has shown robust and durable efficacy for the front-line treatment of gastrointestinal stromal tumours (GIST). 1 However, long-term use of imatinib is often limited by side-effects, medical comorbidities, cost, and patient desire for a drug holiday. In The Lancet Oncology, Jean-Yves Blay and colleagues report results from the BFR14 trial investigating the discontinuation of imatinib in patients with advanced GIST. 2 Patients with a complete response, a partial response, or stable disease at 1, 3, and 5 years were randomly assigned to stop imatinib and restart on progression (interruption group) versus continue treatment until disease progression (continuation group). The study previously showed improved progression-free survival in the continuation group. 3 Now with follow-up of 235·2 months (IQR 128·8–236·6) after the 1-year randomisation, 200·9 months (190·2–208·4) after the 3-year randomisation, and 164·5 months (134·4–176·4) after the 5-year randomisation, Blay and colleagues report on updated overall survival and time to imatinib resistance, defined as the time from randomisation to progression on imatinib or last follow-up. They show that overall survival was significantly improved in the continuation group versus the interruption group at 3 years (104·0 months [95% CI 90·7–118·7] vs 134·0 months [89·7–178·3]; hazard ratio [HR] 0·40 [95% CI 0·20–0·82], log-rank p=0·0096), whereas time to imatinib resistance was significantly shorter in patients in the interruption group than in the continuation group at 3 years (66·2 months [95% CI 43·0–89·6] vs 127·X months [15·0–239·7]; HR 0·35 [95% CI 0·17–0·72], log-rank p=0·0028) and 5 years (58·6 months [0–167·4] vs not reached [NR; NR–NR]; 0·24 [0·05–1·12], log-rank p=0·049). This long-term follow-up from a randomised trial confirms the practice of continuous suppression of the oncogenic driver in advanced GIST.
The Lancet Oncology 2023