ARROW Trial Update Continues to Support Pralsetinib Use, Biomarker Testing in RET Fusion+ NSCLC

A positive efficacy and safety profile persists with pralsentinib in RET fusion–positive non–small cell lung cancer, according to data presented at the 2021 ASCO Annual Meeting.

Durable responses coupled with a tolerable safety profile of pralsetinib (Gavreto) in patients with RET fusion–positive non–small cell lung cancer (NSCLC) was reported from the ARROW trial (NCT03037385) at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, further supporting use of the agent in this patient subset.1

Initial findings from the phase 1/2 trial led to the accelerated approval of the agent in the indicated patient population.2 RET fusion–positive disease represents 1% to 2% of all NSCLC tumors.

“These data are important because [they] support the importance of early biomarker testing for all patients with metastatic NSCLC prior to treatment initiation to inform optimal healthcare decisions,” said Giuseppe Curigliano, MD, PhD, associate professor of medical oncology at the University of Milano in Italy and head of the division of early drug development at the European Institute of Oncology in Italy, at the 2021 virtual ASCO Annual Meeting about updated data from the ARROW trial.

The phase 1/2 study was conducted at 84 sites in 13 countries. In particular, the safety population for this study included 233 patients with RET fusion-positive NSCLC and 238 patients with other RET-altered solid tumors. In particular, 216 patients (median age, 60 years; 48% men) with RET fusion-positive NSCLC had measurable disease.

Originally patients who were treatment-naïve were not eligible, which was a requirement that was later removed by a protocol amendment. There were 25 patients who were enrolled after this eligibility revision (median age, 54 years; 44% men).

The study had a primary end point of objective response rate (ORR). Follow-up was conducted for a median of 17.1 months.

For the 216 patients who received pralsentinib and were RET fusion-positive, the ORR was 69% (95%, CI, 62-75), DCR was 92% (95%, CI; 87-95), CBR was 77% (95%, CI; 71-82) and median duration of response (DOR) was 22.3 months (95%, CI; 15.1-not reached).

In the post-eligibility population with 25 patients, the ORR was 88% (95% CI, 69-98), CBR was 88% (95% CI, 69-98), DCR was 96% (95% CI, 80-100). In addition, median DOR and median PFS was not reached.

“The most important observation is that in the expansion cohort of real-world and first-line treatment of (non-small cell lung cancer) patients with RET fusion-positive tumor, the overall response rate was 88%, providing support for RET inhibitor as a first-line standard of care because the response rate was better in this population (with) respect to the previous eligibility criteria population,” Curigliano said.

The median duration of response in patients with prior platinum-based chemotherapy was 22.3 months (95% CI, 15.1-not reached). Curigliano added that it was too early to analyze data regarding the duration of response in treatment-naïve patients.

Overall, 26 patients (6%) out of 471 patients in the entire study discontinued treatment due to treatment-related adverse events. In all tumor types, 15% of patients had treatment-related neutropenia leading to treatment interruption whereas 14% had neutropenia from the treatment which resulted in a dose reduction. Less than 1% of patients discontinued treatment from treatment-related neutropenia.

“It means that pralsentinib was very well tolerated,” Curigliano said.


1. Curigliano, G, Gainor JF, Griesinger F, et al. Safety and efficacy of pralsetinib in patients with advanced RET fusion-positive non-small cell lung cancer: Update from the ARROW trial. Presented at: 2021 ASCO Annual Meeting; June 4-8, 2021; Virtual. Abstract 9089.

2. FDA approves pralsetinib for lung cancer with RET gene fusions. FDA. September 4, 2021. Accessed June 4, 2021.