FDA Expands Arsenal of Oncology/Hematology Medicines in June

New BRAF/MEK Inhibitor Combo in Melanoma. The Food and Drug Administration (FDA) approved the combination of the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib (Braftovi® and Mektovi®, Array BioPharma Inc) for the treatment of patients with metastatic melanoma with a BRAF V600E or V600K mutation. This approval was based on results from the phase III COLUMBUS trial, in which the combination almost doubled the median overall survival (OS) compared to vemurafenib monotherapy (33.6 months vs 16.9 months; HR 0.61, P<.0001).


Two New Indications for Pembrolizumab. The PD-1 inhibitor pembrolizumab (Keytruda®, Merck) was granted accelerated approval in two new indications: Cervical cancer and primary mediastinal large B-cell lymphoma (PMBCL). In both tumors, continued approval may be contingent on results from confirmatory trials.

  • In cervical cancer, pembrolizumab was granted approval for patients with recurrent or metastatic disease who have disease progression on or after chemotherapy, and whose tumors express PD-L1. This decision was based on results seen in patients with recurrent or metastatic cervical cancer in the phase II Keynote-158 trial. Pembrolizumab treatment resulted in an overall response rate (ORR) of 14.3%, including 2.6% complete responses (CR), and 11.7% partial responses, in PD-L1-positive patients with recurrent or metastatic cervical cancer. No responses were seen in patients whose tumors did not have PD-L1 expression (combined positive score ˂1).
  • In PMBCL, pembrolizumab received accelerated approval for treatment of adult and pediatric patients with refractory PMBCL or those who have relapsed after 2 or more lines of therapy. This approval was based on results from the phase II Keynote-170 trial, where pembrolizumab treatment resulted in an ORR of 45%, including 11% complete responses, in 53 patients with relapsed or refractory PMBCL. Pembrolizumab should not be used in patients who require urgent cytoreductive therapy.
  • Venetoclax Converted to Full Approval in CLL. The accelerated approval of venetoclax (Venclexta®, Abbvie) in patients with chronic lymphocytic leukemia (CLL) with or without 17p deletions at and least 1 prior line of therapy was converted to a full approval, based on results from the confirmatory phase III MURANO trial. Data from the trial showed that at 23 months’ median follow-up the combination of venetoclax and rituximab resulted in significant improvements in median progression-free survival (PFS) compared to bendamustine plus rituximab (not reached versus 18.1 months; HR 0.19, P<.0001). Venetoclax was initially granted approval for this indication in 2016.
  • Bevacizumab Receives Green Light for First-Line Ovarian Cancer. After a long wait, bevacizumab (Avastin®, Genentech) received approval in the United States for use in combination with carboplatin and paclitaxel, followed by single-agent bevacizumab, as first-line treatment following initial surgical resection in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Bevacizumab has been approved for this indication in the European Union since 2011, and was previously approved by the US FDA for treatment of recurrent ovarian cancer. Frontline approval was granted based on results from the phase III GOG-0218 trial, where bevacizumab plus chemotherapy followed by bevacizumab maintenance resulted in a 38% reduction in the risk of disease progression or death compared to chemotherapy alone (median PFS: 18.2 months vs 12.0 months; HR 0.62, P<.0001).
  • First Pegfilgrastim Biosimilar Approved in US. The FDA approved the granulocyte colony-stimulating factor (GCSF) pegfilgrastim-jmdb (Fulphila™, Mylan GmbH), a biosimilar of Neulasta®. Fulphila™ was approved for use in preventing infection in patients with nonmyeloid cancer who are receiving mylosuppressive chemotherapy that has a clinically significant incidence of febrile neutropenia. The approval of Fulphila™ was based on demonstration of similarity to Neulasta® across several domains, including structural and functional characterization, animal study data, human pharmacokinetics and pharmacodynamics, clinical immunogenicity, and clinical safety and efficacy. Fulphila™ has not been approved as an interchangeable product with Neulasta®.


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