Initial US Approval

  • 20201

Indications

  • Adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test.1
  • Adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). [This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s)].1

Recommended Dose/Route

  • 400 mg orally once daily on an empty stomach (no food intake for at least 2 hours before and at least 1 hour after taking pralsetinib)1

Dose Reductions for Adverse Reactions

  • 1st reduction: 300 mg once daily1
  • 2nd reduction: 200 mg once daily1
  • 3rd reduction: 100 mg once daily1
  • Permanently discontinue pralsetinib in patients who are unable to tolerate 100 mg taken orally once daily.

Pivotal Study

  • ARROW (NCT03037385)2,3
  • Key Inclusion Criteria: Eligible participants included patients with metastatic RET fusion-positive NSCLC who had progressed on platinum-based chemotherapy and treatment-naïve patients with metastatic NSCLC.1
  • Treatment: Pralsetinib 400 mg orally once daily until disease progression or unacceptable toxicity.1
Pralsetinib: Efficacy Data

Pralsetinib: Efficacy Data

Safety

  • Common Adverse Reactions ( >20%): The most frequently reported adverse events (AEs) were constipation (45%), edema (44%), musculoskeletal pain (44%), fatigue (42%), hypertension (38%), cough (36%), diarrhea (30%), pyrexia (29%), pneumonia (24%), and dyspnea (21%).1
  • Common Laboratory Abnormalities (>20%): The most frequently reported lab abnormalities were increase AST (80%), decreased leukocytes (79%), decrease hemoglobin (78%), decreased lymphocytes (73%), decreased neutrophils (70%), increased ALT (58%), decreased albumin (52%), decreased calcium (50%), decreased phosphate (50%), increased creatine (45%), increased alkaline phosphate (43%), decreased sodium (42%), decreased platelets (33%), decreased potassium (27%), increased potassium (27%), decreased magnesium (25%), and increased bilirubin (20%).
  • Dosage Interruption Due to AEs: 73%1
  • Dosage Reduction Due to AEs: 51%1
  • Permanent Discontinuation Due to AEs: 20%1

References

  1. Gravreto (pralsetinib). Prescribing information. Rigel Pharmaceuticals, Inc., 2024. Accessed November 18, 2024. https://gavreto-hcp.com/downloads/pdf/GAVRETO-Full-Prescribing-Information.pdf
  2. Gainor JF, Curigliano G, Kim DW, et al. Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study. Lancet Oncol. 2021;22(7):959-969. doi:10.1016/S1470-2045(21)00247-3
  3. Subbiah V, Cassier PA, Siena S, et al. Pan-cancer efficacy of pralsetinib in patients with RET fusion-positive solid tumors from the phase 1/2 ARROW trial. Nat Med. 2022;28(8):1640-1645. doi:10.1038/s41591-022-01931-y
  4. Occurrence and management of selpercatinib- and pralsetinib-related AEs in patients with RET fusion-positive mNSCLC. Targeted Oncology. January 20, 2023. Accessed November 18, 2024. https://www.targetedonc.com/view/occurrence-and-management-of-selpercatinib--and-pralsetinib-related-aes-in-patients-with-ret-fusion-positive-mnsclc
  5. Nardo M, Gouda MA, Nelson BE, et al. Strategies for mitigating adverse events related to selective RET inhibitors in patients with RET-altered cancers. Cell Rep Med. 2023;4(12):101332. doi:10.1016/j.xcrm.2023.101332