FDA approvals for NSCLC and lymphoma

New Treatments Available in the United States for BRAF-Mutated NSCLC and B-Cell Malignancies

On 22 June 2017, the United States Food and Drug Administration (FDA) granted approval to the combination of the BRAF and MEK inhibitors dabrafenib and trametinib (Tafinlar® and Mekinist®, Novartis) for patients with metastatic non-small cell lung cancer (NSCLC) harboring BRAF V6000E mutation detected by an FDA approved test. Approval was also granted to a subcutaneous (SC) formulation of rituximab/hyaluronidase human (Rituxan Hycela™, Genentech) for certain B-cell malignancies. Both of these treatment options are also approved in Europe.

The combination of dabrafenib and trametinib has previously been approved for use in patients with BRAF-mutated metastatic melanoma. The approval in NSCLC was based on results from an international, multicenter, nonrandomized, phase II, open-label study, which examined dabrafenib 150 mg twice daily and trametinib 2 mg once daily in both treatment-naïve and previously treated patients with metastatic BRAF-mutated NSCLC. The overall response rate (ORR) was 61% in treatment-naïve patients and 63% in previously treated patients. The median duration of response (DoR) was not estimable in treatment-naïve patients and was 12.6 months in previously treated patients. The adverse event (AE) profile for the combination was similar to that seen in melanoma. The most common grade 3/4 AEs were pyrexia, fatigue, dyspnea, vomiting, diarrhea, rash, and hemorrhage. A next-generation sequencing (NGS) panel for the detection of multiple gene mutations including BRAF, the Oncomine™ Dx Target Test (Thermo Fisher Scientific), was approved as a companion diagnostic to select patients with BRAF V600E mutations for treatment with dabrafenib and trametinib. This is the first FDA-approved NGS panel for detection of multiple gene mutations or alterations (BRAF, ROS1, and EGFR) in a single test from a single tissue specimen.

A subcutaneous (SC) formulation of rituximab comprising the combination of rituximab and the dispersion agent hyaluronidase human (Rituxan Hycela™, Genentech Inc.) was approved for use in adults with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL) in the indications for which rituximab is approved. This novel formulation shortens the administration time from several hours with intravenous (IV) infusion to five to seven minutes subcutaneously. Approval was based on multiple randomized clinical trials that demonstrated comparable efficacy and safety of SC rituximab compared with IV rituximab, as well as noninferior rituximab concentration levels following the different routes of administration. With the exception of local skin reactions, the incidence and AE profile of SC formulation was similar to that of IV rituximab. SC rituximab is approved at fixed doses of 1400 mg rituximab/23,400 units of hyaluronidase human for patients with either FL or DLBCL and 1600 mg of rituximab/26,800 units of hyaluronidase human for patients with CLL. Patients should receive at least one complete dose of IV rituximab before receiving SC rituximab.