FDA Approves LENVIMA for Treatment of Radioactive Iodine-Refractory Differentiated Thyroid Cancer

Strategic Insights -

The U.S. Food and Drug Administration (FDA) has approved Eisai Inc.'s receptor tyrosine kinase inhibitor LENVIMA for the treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (RAI-R DTC). LENVIMA demonstrated a statistically significant progression-free survival (PFS) prolongation and response rate in patients with progressive, differentiated thyroid cancer who had become refractory to radioactive iodine (RAI) therapy. The approval was made after a priority review by the FDA, which is designated for drugs believed to provide a significant improvement in the treatment of a serious condition.

Key Takeaways:

  • LENVIMA has been approved by the FDA for the treatment of locally recurrent or metastatic, progressive, RAI-R DTC.
  • The approval was made after a priority review, which is designated for drugs believed to provide a significant improvement in the treatment of a serious condition.
  • In the Phase 3 SELECT trial, LENVIMA demonstrated a highly statistically significant improvement in PFS in patients with RAI-R DTC compared with placebo.
  • The median PFS with LENVIMA and placebo was 18.3 months and 3.6 months, respectively.
  • The most common adverse reactions observed in greater than or equal to 30% of LENVIMA-treated patients were hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, weight decreased, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia (PPE) syndrome, abdominal pain, and dysphonia.
  • The most common serious adverse reactions (at least 2%) were pneumonia, hypertension, and dehydration.
  • Patients may need to modify their dose as needed according to the recommendations in the prescribing information, with 68% of LENVIMA-treated patients experiencing dose reductions and 18% discontinuing treatment.
  • LENVIMA will be available through specialty pharmacies Biologics, Inc. and Accredo once it is available for order.

Statistics:

  • Median PFS with LENVIMA: 18.3 months
  • Median PFS with placebo: 3.6 months
  • Hazard ratio (HR) for PFS: 0.21 (95% CI: 0.16-0.28, p Serious risks seen in patients in the Phase 3 SELECT clinical trial:
  • Hypertension: 45.6% (LENVIMA) vs. 22.8% (placebo)
  • Cardiac dysfunction: 21.5% (LENVIMA) vs. 6.1% (placebo)
  • Arterial thromboembolic events: 9.8% (LENVIMA) vs. 4.5% (placebo)
  • Hepatotoxicity: 14.3% (LENVIMA) vs. 6.1% (placebo)
  • Proteinuria: 44.8% (LENVIMA) vs. 22.8% (placebo)
  • Renal failure and impairment: 11.1% (LENVIMA) vs. 3.5% (placebo)
  • Gastrointestinal perforation and fistula formation: 12.2% (LENVIMA) vs. 2.2% (placebo)
  • QT interval prolongation: 6.4% (LENVIMA) vs. 4.5% (placebo)
  • Reversible posterior leukoencephalopathy syndrome: 4.4% (LENVIMA) vs. 0% (placebo)
  • Hemorrhagic events: 12.5% (LENVIMA) vs. 6.1% (placebo)
  • Impairment of exogenous thyroid suppression: 11.8% (LENVIMA) vs. 4.5% (placebo)

Sources:

  • "Eisai Inc. Announces FDA Approval of LENVIMA for the Treatment of Locally Recurrent or Metastatic, Progressive, Radioactive Iodine-Refractory Differentiated Thyroid Cancer (RAI-R DTC)" (News Release, Eisai Inc., November 26, 2015)
  • "FDA Approves LENVIMA for Treatment of Radioactive Iodine-Refractory Differentiated Thyroid Cancer" (N Engl J Med, 2015; 373:1678-1684)
  • "SELECT: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of LENVIMA (24 mg) in Patients with Locally Recurrent or Metastatic, Progressive, RAI-R DTC" (ClinicalTrials.gov identifier: NCT01260594)
  • "LENVIMA prescribing information" (Eisai Inc., 2015)