EMA Positive Opinions in July For New Anticancer Therapies in Europe

On 26 July, the European Medicines Agency (EMA) issued several positive opinions recommending the approval of new agents for anticancer indications in Europe.

  • Durvalumab, First Immunotherapy for Locally Advanced NSCLC. The immune checkpoint inhibitor durvalumab (Imfinzi®, AstraZeneca) received a positive opinion for treatment of PD-L1-positive (>1%) patients with locally advanced unresectable non-small cell lung cancer (NSCLC) who have not progressed following chemoradiation. This approval was based on results from the phase III PACIFIC trial, in which durvalumab following chemoradiation resulted in a significant improvement in progression-free survival and overall survival (OS) compared to chemoradiation alone in patients with unresectable stage III NSCLC. Unlike the approval by the US Food and Drug Administration (FDA) in February of this year, the EMA recommends use of durvalumab for patients with >1% PD-L1 expression on tumor cells.
  • Two New Indications for Pembrolizumab. The EMA issued positive opinions for the use of pembrolizumab (Keytruda®, Merck Sharp & Dohme) in two new indications, including use in combination with pemetrexed and platinum chemotherapy for first-line treatment of patients with metastatic non-squamous NSCLC and as a monotherapy in patients with previously treated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with >50% PD-L1 expression. The opinion in first-line non-squamous NSCLC was based on the results from phase III Keynote-189 trial, in which combination pembrolizumab and chemotherapy resulted in a significant improvement in OS and PFS compared to chemotherapy alone in previously untreated patients, regardless of PD-L1 expression status. In HNSCC, the positive opinion was based on results from the Keynote-040 trial, in which pembrolizumab treatment resulted in significantly improved outcomes compared to standard of care in patients with PD-L1 expressing tumors. Among HNSCC patients with PD-L1 expression in more than 50% of cancer cells, the median OS was 11.6 months, versus 7.9 months with standard of care (HR 0.54, P = .0017).
  • Adjuvant Dabrafenib/Trametinib Combo After Surgery for BRAF-Mutant Melanoma. The combination of dabrafineb and trametinib (Tafinlar® and Mekinist®, Novartis) received a recommendation for use as adjuvant therapy following complete resection in patients with BRAF V600E mutated stage III melanoma. In the phase III COMBI-AD trial, the dabrafenib and trametinib combination resulted in a 53% reduction in risk of recurrence or death compared to placebo in patients with BRAF-mutated stage III melanoma.
  • New BRAF/MEK Inhibitor Combination Approved for First-Line Metastatic Melanoma. The BRAF inhibitor encorafenib and the MEK inhibitor binimetinib (Braftovi® and Mektovi®, Pierre Fabre Medicament) received a positive opinion for the treatment of patients with BRAF V600 mutation-positive metastatic melanoma. In the phase III COLUMBUS trial, the combination of encorafenib and binimetinib resulted in a 7.6-month improvement in PFS, compared to vemurafenib monotherapy (14.9 months vs 7.3 months; HR 0.54, P<.0001) and an OS of more than 30 months; the highest achieved by a targeted therapy in metastatic melanoma (33.6 months vs 16.9 months). This is the first approval for these agents in melanoma.
  • First-Line Daratumumab Combo for Myeloma. The EMA recommended expanding the indication of daratumumab (Darzalex®, Janssen-Cilag International) to include use in combination with bortezomib, melphalan, and prednisone (VMP) in transplant-ineligible patients with newly diagnosed multiple myeloma. This decision was based on results from the phase III ALCYONE study, where the addition of daratumumab to VMP in transplant-ineligible patients resulted in a 50% reduction in the risk of progression or death.
  • Blinatumomab Recommended for Pediatric ALL. The CD19-targeted bispecific T-cell antibody blinatumomab (Blincyto®, Amgen Europe) received a positive opinion for expansion of its indication in Philadelphia chromosome (Ph)-negative CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) to include pediatric patients aged 1 year or older who are in relapse or refractory following at least two prior therapy or in relapse after prior stem cell transplant. Data supporting this recommendation came from the phase I/II Study 205, where blinatumomab resulted in complete remission within two cycles in 39% of patients.

EMA-opinions-July-2018