Pralsetinib in RET fusion-positive non-small-cell lung cancer: a real-world data (RWD) analysis from the Italian expanded access program (EAP)
Menée en Italie dans un contexte de vie réelle à partir de données portant sur 62 patients atteints d'un cancer du poumon non à petites cellules présentant une fusion du gène RET (âge médian : 62 ans ; durée médiane de suivi : 10,1 mois), cette étude rétrospective évalue l'efficacité, du point de vue du taux de réponse objective et de la survie sans progression, et la toxicité du pralsétinib (un inhibiteur de RET)
Objectives : The selective RET-inhibitor pralsetinib has shown therapeutic activity in early clinicaltrials in patients with non-small cell lung cancer (NSCLC) harboring rearranged during transfection (RET) gene fusions. To date, the real-world efficacy of pralsetinib in this populationis unknown. Materials and methods : A retrospective efficacy and safety analysis was performed on data from patients with RET-fusion positive NSCLC enrolled in the pralsetinib Italian expanded access programbetween July 2019 and October 2021. Results : Overall, 62 patients with RET-fusion positive NSCLC received pralsetinib at 20 Italian centers. Next-generationsequencing was used to detect RET alterations in 44 patients (73%). The most frequent gene fusion partner was KIF5B (75% of 45 evaluable). Median age was 62 years (range, 36–90), most patients werefemale (57%) and never smokers (53%). Brain metastases were known in 18 patients (29.5%)at the time of pralsetinib treatment. 13 patients were treatment naïve (unfit forchemotherapy), 48 were pretreated (median number of previous lines: 1, range, 1–4).The objective response rate (ORR) was 66% [95% confidence interval (CI), 53–81] inthe evaluable population (n=59). The disease control rate (DCR) was 79%. After a median follow-up of 10.1 months, the median progression free survival was 8.9 months (95%CI,4.7–NA). In patients with measurable brain metastases (n=6) intracranial ORR was 83%,intracranial DCR was 100%. Overall, 83.6% of patients experienced any-grade treatment-relatedadverse events (TRAEs), 39% grade 3 or greater (G≥3). The most common G≥3 TRAEs wereneutropenia (9.8%), dry mouth/oral mucositis (8.2%), and thrombocytopenia (6.6%).Seven patients (12%) discontinued pralsetinib due to TRAEs, twenty-six had at leastone dose level modification due to TRAEs. Two treatment-related deaths were observed(1 sepsis, 1 typhlitis). Conclusions : In the real-world setting, pralsetinib confirmed durable systemic activity and intracranial response in RET-fusion positive NSCLC. Toxicity profile was consistent with previous reports.
Lung Cancer 2022