Clinical factors driving use of RET inhibitor pralsetinib and associated real-world outcomes in RET fusion–positive NSCLC: A retrospective chart review.

e20731 Background: Selective RET (REarranged during Transfection) inhibitors (RETi) have become standard treatment for RET fusion-positive non-small cell lung cancer ( RET + NSCLC), which represent 1–2% of NSCLC cases. Clinical factors that drive front-line versus later-line RETi use and outcomes are not well understood. This retrospective chart review evaluates physician decision drivers alongside real-world effectiveness and safety for pralsetinib (PRAL) in RET + NSCLC. Methods: A retrospective chart review was conducted via a standardized web-based form among US oncologists treating advanced RET + NSCLC. Eligible patients initiated PRAL for RET + NSCLC between October 2020 and December 2024. Data gathered included physician treatment considerations, patient baseline characteristics, and efficacy outcomes. Results: Eighty-two charts from patients who received PRAL as their first (index) RETi were collected from 43 physicians across both academic (41.9%) and community (58.1%) sites. Of the 82 patients, 51.2% received PRAL front line (1L) and 31.7% in the second line (2L). From a predefined list, physicians most often cited comorbidities (36.6%) and ECOG performance status (31.7%) as clinical factors when considering index PRAL therapy and efficacy profile (56.1%), followed by intracranial activity (24.4%) and hypersensitivity to immuno-oncology agents (24.4%) as therapy-related considerations. Although not a primary therapy selection driver, in 13 patients with safety as a consideration, 6 (46.2%) had myelosuppression noted as a concern for index PRAL treatment. RET + NSCLC patients treated in the 1L setting with PRAL had an overall response rate (ORR) of 73.8% (14 CR; 17 PR). For 2L line PRAL, the ORR was 61.5% (1 CR; 15 PR). Anemia (17.1%), diarrhea (13.4%), and constipation (13.4%) were the most frequently reported adverse events (AE). Discontinuation was mainly due to loss of/no response (80.6%), insurance (16.1%), and AEs (3.2%). The single PRAL patient that discontinued due to an AE had edema. There were an additional 7 patients that switched to PRAL due to an AE on a different RETi. The post-switch ORR was 57.1% (4/7); of these patients, 3 maintained their previous response and 1 improved their response. Conclusions: In this retrospective chart review, pralsetinib was used across treatment lines with high real-world response rates, consistent with results from the ARROW trial. Treatment selection was influenced by specific clinical factors including patient comorbidities, ECOG performance status, and safety concerns, with AE-driven switching uncommon yet associated with continued responses.