Reference Detail

Ref Type

Journal Article

PMID

(36379124)

Authors

Passaro A, Russo GL, Passiglia F, D'Arcangelo M, Sbrana A, Russano M, Bonanno L, Giusti R, Metro G, Bertolini F, Grisanti S, Carta A, Cecere F, Montrone M, Massa G, Perrone F, Simionato F, Guaitoli G, Scotti V, Genova C, Lugini A, Bonomi L, Attili I, de Marinis F

Title

Pralsetinib in RET fusion-positive non-small-cell lung cancer: A real-world data (RWD) analysis from the Italian expanded access program (EAP).

Journal	Vol	Issue	Date	Pages	Journal Short Title
Lung cancer (Amsterdam, Netherlands)	174		2022 Nov 09	118-124	Lung Cancer

URL

Abstract Text

The selective RET-inhibitor pralsetinib has shown therapeutic activity in early clinical trials 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 population is unknown.A retrospective efficacy and safety analysis was performed on data from patients with RET-fusion positive NSCLC enrolled in the pralsetinib Italian expanded access program between July 2019 and October 2021.Overall, 62 patients with RET-fusion positive NSCLC received pralsetinib at 20 Italian centers. Next-generation sequencing 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 were female (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 for chemotherapy), 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] in the 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-related adverse events (TRAEs), 39 % grade 3 or greater (G ≥ 3). The most common G ≥ 3 TRAEs were neutropenia (9.8 %), dry mouth/oral mucositis (8.2 %), and thrombocytopenia (6.6 %). Seven patients (12 %) discontinued pralsetinib due to TRAEs, twenty-six had at least one dose level modification due to TRAEs. Two treatment-related deaths were observed (1 sepsis, 1 typhlitis).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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
RET fusion	lung non-small cell carcinoma	sensitive	Pralsetinib	Clinical Study	Actionable	In a retrospective study, Gavreto (pralsetinib) treatment resulted in an objective response rate (ORR) of 61% (39/59, 2 complete responses (CR), 37 partial responses (PR)) and a disease control rate (DCR) of 79.7% in non-small cell lung cancer patients harboring RET fusions, and an intracranial ORR of 66.7% (4/6, 3 CR and 1 PR), an intracranial DCR of 100% in patients with measurable brain metastases (PMID: 36379124).	36379124