NTRK gene fusions: a rough diamond ready to sparkle

Menée à partir des données de 3 essais cliniques de phase I/II incluant au total 159 patients, adultes et pédiatriques, atteints d'une tumeur solide de stade avancé et présentant une fusion du gène NTR, cette étude évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité du larotrectinib, un inhibiteur sélectif de TRK

Résumé en anglais

The identification of oncogenic fusions and the development of selective tyrosine kinase inhibitors have revolutionised the therapeutic approach for several solid tumours. Neurotrophic tropomyosin receptor kinase (NTRK) rearrangements have been described in most solid tumours, with variable frequencies, ranging from less than 1% in high-prevalence tumours (eg, non-small-cell lung cancer [NSCLC] and breast cancer), to 5–25% in some tumour types (eg, papillary thyroid cancer and Spitzoid neoplasms), to more than 90% in uncommon histotypes (eg, secretory breast carcinoma and mammary analogue secretory carcinoma). Multiple TRK inhibitors with different properties are available or under clinical development ( table). Larotrectinib was the first-in-class TRK inhibitor approved for metastatic, inoperable NTRK fusion-positive solid tumours and the second tumour-agnostic US Food and Drug Administration (FDA)-approved drug, based on the impressive results of three open-label, single-group, phase 1/2 studies. The preliminary analysis of the first 55 patients enrolled in the phase 1 studies showed a 75% overall response by independent review committee, with median duration of response and median progression-free survival not reached. Larotrectinib was also well tolerated, with most adverse events being of grade 1–2 severity, and no treatment-related adverse events of grade 3–4 in 5% or more of the patients.