EMA Issues 4 Positive Opinions

EMA Adopted Positive Opinions for Five Anticancer Medicines in the Past Two Months

On 23 February 2017, the European Medicines Agency (EMA) announced their support for the approval of dabrafenib and trametinib in combination for BRAF-mutant non-small cell lung cancer (NSCLC), daratumumab combinations for multiple myeloma, and rolapitant for chemotherapy-induced nausea and vomiting (CINV).

  • The combination of dabrafenib and trametinib (Tafinlar® and Mekinist®, Novartis) was recommended for approval for the treatment of patients with advanced NSCLC harboring BRAF V600 This approval is based on results from a phase II multicenter non-randomized trial that included 57 patients with metastatic BRAF mutation–positive NSCLC who had progressed on at least one line of platinum-based chemotherapy. The combination of dabrafenib and trametinib resulted in an overall response rate (ORR) of 63.2%, including two complete responses (CR), and a disease control rate of 79%. The median duration of response was 9.0 months and the median progression-free survival (PFS) was 9.7 months. Overall survival (OS) data are not yet mature, but the 6-month OS rate was 82%. Almost all patients experienced at least one treatment-related adverse event (AE), and half (49%) experienced a grade 3/4 AE. The most common serious AEs were pyrexia (16%), anemia (5%), and at 4% each, confusion, decreased appetite, hemoptysis, hypercalcemia, nausea, and squamous cell carcinoma of the skin. Most of the grade 3/4 AEs were manageable with dose modifications and interruptions. Of note, this combination has not yet been approved by the US Food and Drug Administration (FDA) for NSCLC.
  • The indication of daratumumab (Darzalex®, Janssen) was extended to include use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for multiple myeloma that has progressed on at least one prior therapy. These indications are based on results from the phase III CASTOR and POLLUX. Daratumumab has previously been approved as a monotherapy for patients with relapsed/refractory multiple myeloma who have previously been treated with both a proteasome inhibitor and an immunomodulatory agent (IMiD).
  • The oral formulation of rolapitant (Varuby®, Tesaro), a neurokinin 1 receptor agonist, received a positive opinion for the prevention of delayed nausea and vomiting associated with highly and moderately emetogenic cancer chemotherapy. This agent has been available in the United States since September 2015.

In addition, on 23 March 2017, the EMA announced positive opinions for the programmed death receptor 1 (PD-1) inhibitors nivolumab for squamous cell carcinoma of the head and neck (HNSCC), and pembrolizumab for Hodgkin lymphoma. Both nivolumab and pembrolizumab were previously approved by the FDA for these indications.

  • Nivolumab (Opdivo®, Bristol-Meyers Squibb) received a positive opinion for an indication extension to include use as monotherapy in adults with HNSCC who progressed on or after platinum-based therapy. Nivolumab is currently approved in Europe for indications in NSCLC, melanoma, renal cell carcinoma (RCC), and classic Hodgkin lymphoma.
  • The EMA recommended extension of the indication of pembrolizumab (Keytruda®, Merck) to include use as monotherapy for patients with relapsed or refractory Hodgkin lymphoma who have failed both autologous stem cell transplant (ASCT) and brentuximab vedotin, or who are transplant-ineligible and have failed brentuximab vedotin. Pembrolizumab is currently approved in Europe for use in melanoma and NSCLC.