Important New FDA Approvals in May for Patients With Cancer

  • Combo Dabrafenib/Trametinib for BRAF-Mutated Thyroid Cancer. The United States Food and Drug Administration (FDA) expanded the indication of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib (Tafinlar® and Mekinist®, Novartis) in combination to include use in patients with BRAFV600E-mutated anaplastic thyroid cancer. This approval was based on results from a multicohort, nonrandomized, phase II trial that examined this combination in patients with BRAFV600E mutations across a variety of solid tumors. In patients with advanced anaplastic thyroid cancer, dabrafenib/trametinib resulted in an overall response rate (ORR) of 61%, including 4% complete response and 57% partial response. In 64% of responding patients, responses lasted for longer than 6 months. The adverse event (AE) profile was consistent with the known safety profile of dabrafenib/trametinib.
  • New CAR T-Cell Treatment for Relapsed/Refractory Large B-Cell Lymphoma. The CD19-targeting chimeric antigen receptor modified (CAR) T-cell, tisagenlecleucel (Kymriah™, Novartis), was approved for treatment of relapsed/refractory large B-cell lymphoma following progression on 2 or more lines of systemic therapy. This approval includes use in diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. Approval was based on the phase II JULIET study, in which tisangenlecleucel induced an ORR of 50% and complete recovery (CR) rate of 32% in patients with relapsed/refractory DLBCL. Severe cytokine release syndrome occurred in 23% of patients receiving tisagenlecleucel, and 18% experienced grade 3/4 neurologic toxicity. Tisangenlecleucel was previously approved for treatment of patients aged 25 years and younger with refractory B-cell precursor acute lymphoblastic leukemia (ALL).
  • First-Line Daratumumab Gets Green Light in Transplant-Ineligible Multiple Myeloma. The CD38-targeting antibody daratumumab (Darzalex®, Janssen) received approval for use in combination with bortezomib, melphalane, and prednisone (VMP) for treatment of transplant-ineligible patients with newly diagnosed multiple myeloma. In the phase III ALCYONE trial, the addition of daratumumab to VMP in transplant-ineligible patients resulted in a 50% reduction in the risk of progression or death, compared to VMP alone (HR 0.5, P<.0001). The AE profile was consistent with the known safety profile of daratumumab in multiple myeloma.
  • Avatrombopag for Treatment of Liver-Associated Thrombocytopenia. The FDA approved the second generation thrombopoietin receptor agonist, avatrombopag, (Doptelet®, AkaRx Inc) for treatment of thrombocytopenia in patients with chronic liver disease who are scheduled for a medical or dental procedure. This decision was based on results from two international, multicenter, phase III trials, ADAPT-1 (N = 231) and ADAPT-2 (N = 204). These trials compared avatrombopag at two dose levels (60 mg and 40 mg) administered orally over 5 days to placebo in patients with chronic liver disease with a platelet count less than 40,000/uL and 40,000/uL – 50,000/µL who were scheduled to undergo a procedure. In both studies, avatrombopag at either dose significantly increased the proportion of patients who did not require platelet transfusions, or any rescue procedures for bleeding up to 7 days following a scheduled procedure. The most common AEs in patients treated with avatrombopag were pyrexia, abdominal pain, nausea, heachache, fatigue, and peripheral edema.

FDA-approvals-May-2018