Rapid Readouts: Safety and Efficacy of Pralsetinib in Patients with Advanced RET Fusion-Positive Non-Small Cell Lung Cancer: Update from the ARROW trial

Stephen V. Liu, MD, presents data from the 2021 American Society of Clinical Oncology annual meeting on the updated results from the ARROW trial of pralsetinib in patients with RET fusion-positive non-small cell lung cancer.

Stephen V. Liu, MD, discusses data from the following presentation:

  • Safety and efficacy of pralsetinib in patients with advanced RET fusion–positive non–small cell lung cancer: update from the ARROW trial (Curigliano, ASCO 2021, abstract 9089)
  • The objective of this study is to report the updated outcomes from the ARROW trial of pralsetinib in advanced RET fusion–positive NSCLC (NCT03037385).
  • Phase 1/2 trial:
    • The original study protocol required all treatment-naive patients to not be candidates for standard platinum-based therapy, generally due to age, comorbidities, or other poor prognostic factors. An eligibility revision in July 2019 allowed enrollment of treatment-naive patients who were candidates for standard platinum-based therapy.
    • Phase 1 dose escalation resulted in phase 2 dose of 400 mg once daily
    • Primary end points: overall response rate (ORR; blinded independent central review per RECIST v1.1), safety
    • Secondary end points: duration of response (DOR), clinical benefit rate (CBR), disease control rate (DCR), progression-free survival (PFS), overall survival
  • Conclusions: efficacy
    • ORR: treatment naive (n = 68), 79%; prior platinum (n = 126), 62%; prior nonplatinum (n = 22), 73%
    • DCR: treatment naive, 93%; prior platinum, 91%; prior nonplatinum, 91%
    • CBR: treatment naive, 82%; prior platinum, 74%; prior nonplatinum, 77%
    • Median DOR: treatment naive, not reached (NR); prior platinum, 22.3 mo; prior nonplatinum, NR
    • Median PFS: treatment naive, 13.0 mo; prior platinum, 16.5 mo; prior nonplatinum, 12.8 mo.
  • Conclusions: safety
    • In the overall safety population (all tumor types), 6% of patients discontinued due to treatment-related adverse effects.
    • Treatment-related neutropenia leading to dose reduction or interruption was reported in 14% and 15% of patients, respectively.
  • Conclusions
    • Pralsetinib showed robust, durable response across RET fusion–positive NSCLC treatment groups.
    • These data support early biomarker testing for all patients with metastatic NSCLC prior to treatment initiation to inform management decisions.
    • Pralsetinib is currently approved for treatment of metastatic RET fusion–positive NSCLC and advanced or metastatic RET-altered thyroid cancers in the United States, and in locally advanced or metastatic NSCLC after platinum-based chemotherapy in China.