EMA Recommendations for Oncology/Hematology Approval in February

On 22 February, the European Medicines Agency (EMA) issued positive opinions for granting marketing authorization for four agents in oncology and hematology. All of these agents have previously been approved for similar indications by the US Food and Drug Administration (FDA).

  • Gemtuzumab Ozogamicin as First-Line Therapy for AML. A CD-33-targeting antibody-drug conjugate, gemtuzuamb ozogamicin (Mylotarg™, Pfizer), received a positive opinion for use in combination with daunorubicin and cytarabine for the treatment of patients (age ≥15 years) with treatment-naïve, CD33-positive acute myeloid leukemia (AML), except acute promyelocytic leukemia (APL). This recommendation is based on the results from the phase III ALFA-0701 study in patients with newly diagnosed AML. Gemtuzumab ozogamicin–based therapy was associated with improved event-free survival (EFS) by nearly six months compared to chemotherapy alone (hazard ratio [HR] 0.58; P = .0003). Adverse events were more frequent in patients receiving gemtuzumab ozogamicin, with hematologic toxicity, particularly persistent thrombocytopenia, being the most common.
  • Bosutinib Recommended for Front-Line Treatment of CML. The EMA suggested extending the indication of the BCR-ABL tyrosine kinase inhibitor bosutinib (Bosulif®, Pfizer) to include newly diagnosed patients with chronic-phase Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). Bosutinib was previously approved for patients with CML who had been treated with one or more tyrosine kinase inhibitors (TKIs) or for whom imatinib, nilotinib, and dasatinib are not considered appropriate treatments. Expansion of the indication to the first-line setting was based on results from the phase III BFORE trial, in which bosutinib improved rates of major molecular response at 12 months compared to the response found with imatinib in previously untreated patients with chronic phase Ph-positive CML (47.2% vs 36.9%, respectively; P = .02).
  • Olaparib Tablets for Maintenance Treatment in Ovarian Cancer. A new formulation of olaparib (Lynparza®, AstraZeneca) as 100 mg and 150 mg tablets was recommended for use as monotherapy maintenance (300 mg per day) for patients with platinum-sensitive, relapsed, high-grade, epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. These formulations will allow for fewer doses throughout the day. The currently approved dose for olaparib is eight 50 mg capsules taken twice daily.
  • Denosumab for Prevention of Skeletal-Related Events for Advanced Malignancies Involving Bone. Extension of an existing indication for the RANKL inhibitor denosumab (Xgeva®, Amgen) was adopted to include prevention of skeletal-related events in patients with multiple myeloma, in addition to the current indication in patients with bone metastases from solid tumors. This is based on the data from the large phase III 482 study, where denosumab showed noninferiority to zoledronic acid in delaying the time to first skeletal-related event in patients with newly diagnosed multiple myeloma (0.98; Pfor noninferiority = .010). There was no difference in overall survival, but median progression-free survival (PFS) with denosumab was improved compared to the PFS found with zoledronic acid (46.1 vs 35.4, HR 0.82, P = .036). In addition, denosumab was associated with fewer renal treatment emergent adverse events compared with zoledronic acid.

In contrast to FDA, the EMA did not support approval of adjuvant neratinib for HER2-positive breast cancer and sunitinib for high-risk early stage renal cell carcinoma (RCC). In the United States, the pan-HER targeted tyrosine kinase inhibitor neratinib (Nerlynx®, Puma Biotechnology) is approved based on results from ExteNET trial for extended adjuvant therapy, following standard adjuvant trastuzumab for patients with early-stage, HER2-positive breast cancer, and sunitinib (Sutent®, Pfizer) is approved based on data from S-TRAC trial for use as adjuvant therapy following nephrectomy in patients with RCC at high risk for recurrence.


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