fda-approvals-june-2019

New Oncology and Hematology Indications Approved by FDA in May

  • PI3K Inhibitor Alpelisib for PIK3CA-mutated Advanced Breast Cancer. The phosphoinositide 3-kinase (PI3K) inhibitor alpelisib (Piqray®, Novartis Pharmaceuticals Corporation) was approved for use in combination with fulvestrant for treatment of postmenopausal patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer following progression on or after an endocrine containing regimen. To be eligible to receive alpelisib, patients must have a PIK3CA mutation in tissue specimens and/or in circulating tumor DNA (ctDNA) detected by the companion diagnostic therascreen® PIK3CA RGQ PCR kit, which was simultaneously approved by the FDA. Approval of alpelisib was based on the phase III SOLAR-1 trial, in which alpelisib and fulvestrant resulted in a median progression-free survival (PFS) of 11.0 months, compared to 5.7 months for fulvestrant and placebo (HR 0.65, P = .001) in patients with HR-positive, HER2-negative, PIK3CA-mutated breast cancer who had progressed on prior endocrine therapy.
  • T-DM1 Approval in Breast Cancer Extended to Adjuvant Setting. The HER2-targeting antibody-drug conjugate (ADC) ado-trastuzumab emtansine (T-DM1) (Kadcyla®, Genentech, Inc) received approval for adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease following neoadjuvant therapy with a taxane and trastuzumab containing regimen. In the phase III KATHERINE trial, adjuvant treatment with T-DM1 resulted in a significant improvement in invasive disease-free survival (iDFS) compared to trastuzumab (HR 0.50, P<.0001) in patients with HER2-positive early breast cancer with residual disease following neoadjuvant therapy.
  • Tumor Treating Fields Plus Chemotherapy, a New Strategy for Unresectable Malignant Pleural Mesothelioma. The FDA granted approval to NovoTTF-100L™ (Novocure), a tumor-treating fields delivery system that uses electric fields tuned to specific frequencies to disrupt solid tumor cancer cell division, in combination with chemotherapy for the first-line treatment of unresectable malignant pleural mesolthelioma (MPM). In the phase II STELLAR trial, the NovoTTF-100L system resulted in a median overall survival (OS) of 18.2 months when given in combination with platinum-based chemotherapy in 80 patients with unresectable MPM. This is the first new treatment for MPM approved in 15 years.
  • Avelumab and Axitinib Combo Approved for RCC. The PD-L1 inhibitor avelumab (Bavencio®, EMD Serono, Inc), was approved for use in combination with axitinib for the first-line treatment of patients with advanced renal cell carcinoma (RCC), regardless of PD-L1 status. This approval was based on results from the phase III JAVELIN Renal 101 trial, in which the combination of avelumab and axitinib resulted in significant improvements in PFS compared to sunitinib in both the total trial population (13.8 months vs 8.4 months; HR 0.69, P = .0002) and in the subgroup of patients who were PD-L1-positive (13.8 months vs 7.2 months; HR 0.61, P = .0001). Results for OS, the secondary endpoint, are not yet mature.
  • Ramucirumab, a New Option for Progressive HCC. The angiogenesis inhibitor ramucirumab (Cyramza®, Eli Lilly and Company) was approved for use as a monotherapy in patients with hepatocellular carcinoma (HCC) who have an alpha fetoprotein (AF) of ≥ 400 ng/mL and have been previously treated with sorafenib. This decision was based on the REACH-2 trial, where ramucirumab plus best supportive care resulted in a median OS of 8.5 months, compared to 7.3 months for best supportive care alone (HR 0.71, P = .020) in patients with AFP-high HCC who had progressed on sorafenib.
  • Lenalidomide Use Expanded to Lymphoma. The FDA expanded the indication of lenalidomide (Revlimid®, Celgene) to include use in combination with rituximab in previously treated patients with follicular lymphoma (FL) or marginal zone lymphoma (MZL). Approval of this chemotherapy-free regimen was based on results from the phase III AUGMENT and phase IIIb MAGNIFY clinical trials. In AUGMENT, the combination lenalidomide results in a 25-month improvement in median PFS compared to rituximab plus placebo (39.4 months vs 14.1 months; HR 0.46, P<.0001) in patients with relapsed or refractory FL or MZL. In the MAGNIFY trial, treatment with lenalidomide and rituximab resulted in an overall response rate (ORR) of 59% for patients with FL and 51% for patients with MZL.
  • Ruxolitinib For Treatment of Graft-Versus-Host Disease. The indication of the JAK2 inhibitor ruxolitinib (Jakafi®, Incyte) was expanded to include treatment of steroid-refractory acute graft-versus-host disease (GVHD) in patients 12 years and older. In Study INCB 18424-271, ruxolitinib at a dose of 5 mg twice daily was evaluated in patients with acute GVHD of grades 2 to 4 occurring after allogeneic stem cell transplantation. Treatment resulted in a 28-day ORR of 100% in patients with grade 2 GVHD, 40.7% for grade 3, and 44.4% for grade 4.
  • Venetoclax Gets Green Light in CLL and SLL. Venetoclax (Venclexta®, AbbVie, Inc) was approved for treatment of adults with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) based on results from the randomized phase 3 CLL14 trial. In this study, the combination of venetoclax with obinituzumab resulted in a significant improvement in PFS compared to the combination of obituzumab and chlorambucil (HR 0.35, P<.001) in patients with previously untreated CLL. Significant improvements were also seen in ORR and rates of minimal residual disease (MRD) negativity with venetoclax and obinutuzumab.
  • Ivosidenib Approval Expanded to First-Line Treatment for Some Patients with AML. Ivosidenib (Tibsovo®, Agios Pharmaceuticals, Inc), an oral isocitrate dehydrogenase inhibitor (IDH), was approved for treatment of newly diagnosed patients with acute myeloid leukemia (AML) with an IDH1 mutation (detected by the Abbott RealTimeTM IDH1 assay) who are at least 75 years of age or have comorbidities that preclude use of intensive induction chemotherapy. Ivosidenib was previously approved for treatment of patients with relapsed/refractory AML. Approval in the first-line setting was based on results from the single-arm, open-label, multicenter AG120-C-001 study, in which 12 of 28 patients (42.9%) achieved complete remission (CR) or CR with partial hematologic recovery (CRh) and 7 of 17 (41.2%) of transfusion-dependent patients achieved transfusion independence.

FDA-approvals-May-2019

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