FDA-approval-prime-oncology

New Therapies Available for Patients With Cancer in the United States

On the last days of April, the US Food and Drug Administration (FDA) approved three new indications for the treatment of patients with advanced cancer, including hepatocellular carcinoma (HCC), anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), and FLT3-positve acute myeloid leukemia (AML).

  • The FDA expanded the indications of regorafenib (Stivarga®, Bayer) to include treatment of patients with HCC who have been previously treated with sorafenib. Treatment options for unresectable HCC are limited and regorafenib is only the second agent approved for this disease and the only one for second-line treatment. Approval was based on results from the international, randomized phase III RESORCE trial that included 573 patients with Child-Pugh A cirrhosis and Barcelona Clinic Liver Cancer stage B or C HCC for whom sorafenib had previously failed. Regorafenib (160 mg daily, 3 weeks on/one week off) improved median overall survival (OS) by almost 3 months compared to the OS observed with placebo (10.6 months vs 7.8 months; HR 0.63, P<.0001). Improvements were also seen in progression-free survival (PFS; 3.1 months vs 1.5 months) and overall response rate (ORR; 11% vs 4%) with regorafenib. The adverse event (AE) profile of regorafenib was similar to that seen in other indications. The most common grade ≥3 AEs included hand-foot skin reaction, diarrhea, fatigue, and hypertension.
  • The oral tyrosine kinase inhibitor (TKI) brigatinib (Alunbrig®, Takeda) received accelerated approval for treatment of patients with metastatic ALK-positive NSCLC who have progressed on or are intolerant to crizotinib. This approval was based on results of tumor response rate and duration of response from the noncomparative, two-arm, phase II ALTA trial in 222 patients. Patients were randomized to brigatinib either 90 mg once daily or 180 mg once daily after 7-day lead-in at 90 mg daily. Treatment with brigatinib resulted in a confirmed (ORR of 48% at 90 mg and 53% at 180 mg and a median PFS of 13.8 months in both arms. Of note, brigatinib was highly active in patients with brain metastases. The intracranial response rate was 42% in the 90-mg arm and 67% in the 180-mg arm. The AE profile of brigatinib was manageable, with pneumonia (5.5%) and interstitial lung disease/pneumonitis (4.6%) as the most common serious AEs. Brigatinib is approved at a dose of 90 mg once daily for the first 7 days, increasing to 180 mg once daily if tolerated.
  • Midostaurin (Rydapt®, Novartis), a FLT3-targeting TKI, was approved for use in combination with cytarabine and daunorubicin induction and cytarabine consolidation in patients with newly diagnosed AML who are FLT3 mutation–positive. Approval was based on the randomized, phase III RATIFY trial in 717 patients with previously untreated FLT3-positive AML, in which midostaurin resulted in 23% reduction in the risk of death compared to the reduction seen with placebo (HR 0.77, P = .016). Adverse events occurring in ≥20% of patients included febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, device-related infection, hyperglycemia, and upper respiratory tract infection. The LeukoStrat CDx FLT3 Mutation Assay was approved as a companion diagnostic for use with midostaurin.

FDA-approval-prime-oncology