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Pralsetinib in RET fusion-positive non-small-cell lung cancer: A real-world data (RWD) analysis from the Italian
Antonio Passaro1, Giuseppe Lo Russo2, Francesco Passiglia3
1Division of Thoracic Oncology, European Institute of Oncology IRCCS, Milan, Italy.
Objectives:
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.
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 program between July 2019 and October 2021.
Results:
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).
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.
Insights
Pralsetinib demonstrated significant efficacy in treating non-small cell lung cancer (NSCLC) with RET gene fusions in a real-world setting. The drug showed durable systemic activity and intracranial response, with a manageable safety profile.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Pralsetinib, a selective RET inhibitor, has shown promise in early clinical trials for non-small cell lung cancer (NSCLC) patients with rearranged during transfection (RET) gene fusions.
- The real-world effectiveness and safety of pralsetinib in this specific patient population remained largely unknown prior to this study.
Purpose of the Study:
- To evaluate the real-world efficacy and safety of pralsetinib in patients with RET-fusion positive NSCLC.
- To assess treatment outcomes, including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and intracranial response.
- To characterize the toxicity profile and treatment-related adverse events (TRAEs) associated with pralsetinib use in a real-world setting.
Main Methods:
- A retrospective analysis was conducted on data from 62 patients with RET-fusion positive NSCLC treated with pralsetinib.
- Patients were enrolled in the pralsetinib Italian expanded access program between July 2019 and October 2021.
- Efficacy and safety data were collected and analyzed, including response rates, survival outcomes, and adverse events.
Main Results:
- The objective response rate (ORR) was 66% in the evaluable population (n=59), with a disease control rate (DCR) of 79%.
- Median progression-free survival (PFS) was 8.9 months. In patients with brain metastases (n=6), intracranial ORR was 83% and intracranial DCR was 100%.
- Treatment-related adverse events (TRAEs) occurred in 83.6% of patients, with 39% experiencing grade 3 or greater events. Common TRAEs included neutropenia and dry mouth.
Conclusions:
- Pralsetinib demonstrated durable systemic activity and significant intracranial response in patients with RET-fusion positive NSCLC in a real-world setting.
- The observed toxicity profile was consistent with previous clinical trial reports, indicating a manageable safety profile.
- These findings support the use of pralsetinib as an effective treatment option for RET-fusion positive NSCLC in routine clinical practice.
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