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, 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.