Abstract 1124P
Background
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 efficacy of pralsetinib in this population in the real-world setting is unknown.
Methods
A retrospective efficacy and safety analysis was performed on data from patients with RET fusion positive NSCLC who were enrolled in the pralsetinib Italian expanded access program (EAP) between July 2019 and October 2021.
Results
Overall, 60 patients with RET fusion positive NSCLC received pralsetinib at 20 centers in Italy. Next-generation sequencing was used to detect RET alterations in 45 patients (75%). The most frequent gene fusion partner was KIF5B (77% of 49 evaluable). Median age was 62 years (range, 36–90), most patients were female (57%) and never smokers (51.7%). Brain metastases were known in 17 patients (28%) at the time of pralsetinib treatment. 13 patients were treatment naïve (not candidate to receive chemotherapy), 47 were pretreated (median number of previous lines was one, range, 1–4). The objective response rate (ORR) was 66% [95% confidence interval (CI), 53–81] in the evaluable population (n=58). 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%, and intracranial DCR was 100%. Overall, 83% of patients experienced any-grade treatment-related adverse events (TRAEs), 42% grade 3 or greater (G≥3). The most common G≥3 TRAEs were neutropenia (10%), oral mucositis (10%), anemia (5%), thrombocytopenia (5%), increased liver enzyme levels (5%) and fatigue (5%). Seven patients (12%) discontinued pralsetinib due to TRAEs, 26 patients had at least one dose level modification due to TRAEs. Two treatment-related deaths were observed.
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Passaro: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Merck Sharp & Dohme, Pfizer, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Janssen, Takeda, Boehringer Ingelheim, Mundipharma, Eli Lilly; Non-Financial Interests, Other, Scientific Committee for Lung Cancer Guideline: AIOM. All other authors have declared no conflicts of interest.