NEW APPROVALS BY EMA

The European Medicines Agency's (EMA's) Committee for Medicinal Products for Human Use (CHMP) recommended multiple anticancer agents for approval at its July meeting.

The CHMP recommended the anti-PD-L1 immunotherapy atezolizumab (Tecentriq, Roche) for the treatment of locally advanced or metastatic urothelial carcinoma as well as the treatment of non–small cell lung cancer (NSCLC).

Atezolizumab has demonstrated durable responses in patients who are ineligible for first-line treatment with cisplatin and when used as a second-line treatment for urothelial carcinoma.

In NSCLC, atezolizumab improved survival compared with docetaxel in patients previously treated with chemotherapy.

The most common side effects are fatigue, decreased appetite, nausea, dyspnea, diarrhea, rash, pyrexia, vomiting, arthralgia, asthenia, and pruritus. Atezolizumab is also associated with immune-related adverse reactions common to this class of immunotherapies, including pneumonitis, hepatitis, colitis, hypothyroidism, hyperthyroidism, and others.

Avelumab

The CHMP also endorsed the anti-PD-L1 immunotherapy avelumab (Bavencio, Merck Serono Europe) for the treatment of Merkel cell carcinoma. Avelumab has demonstrated tumor responses, many of which are prolonged, both in patients who were treated with chemotherapy and in those who were not.

The most common side effects are fatigue, nausea, diarrhea, decreased appetite, constipation, infusion-related reaction, weight decrease, and vomiting. Serious adverse reactions include those that are immune related and those that are infusion related.

Lutetium

The CHMP recommended lutetium oxodotreotide (Lutathera, Advanced Accelerator Applications) for the treatment of well-differentiated gastro-entero-pancreatic neuroendocrine tumors. The tumors must be unresectable or metastatic as well as progressive.

Lutetium is a radiopharmaceutical that targets malignant cells that overexpress subtype 2 somatostatin receptors.

Treatment with lutetium has resulted in improved progression-free survival in comparison with octreotide LAR, a somatostatin receptor agonist, in patients with well-differentiated gastro-entero-pancreatic neuroendocrine tumors.

The most common side effects are nausea, vomiting, hematologic toxicity (thrombocytopenia, lymphopenia, anemia, pancytopenia), fatigue, and decreased appetite.

Midostaurin

The CHMP recommended oral agent midostaurin (Rydapt, Novartis EuroPharm) for the treatment of newly diagnosed acute myeloid leukemia (AML) in patients who test positive for the FLT3 mutation. The drug is a tyrosine kinase inhibitor.

In addition to use in AML patients, midostaurin was recommended for the treatment of aggressive systemic mastocytosis, systemic mastocytosis with associated hematologic neoplasm, and mast cell leukemia.

In AML, midostaurin has improved overall survival rates when used in combination with standard chemotherapy. The most common side effects observed in patients with AML treated with midostaurin are febrile neutropenia, nausea, exfoliative dermatitis, vomiting, headache, petechiae, and pyrexia.

In the other blood cancers listed above, midostaurin has produced responses in the majority of patients. The most common side effects are nausea, vomiting, diarrhea, peripheral edema, and fatigue.

Telotristat Ethyl

The CHMP also recommended the oral therapy telotristat ethyl (Xermelo, Ipsen Pharma) for the treatment of carcinoid syndrome diarrhea in combination with a somatostatin analogue.

Telotristat ethyl inhibits L-tryptophan hydroxylases, which disrupt serotonin biosynthesis. Serotonin is oversecreted in patients with neuroendocrine tumors and carcinoid syndrome and is believed to contribute to the symptoms associated with carcinoid syndrome, according to the EMA.

Telotristat ethyl has been shown to decrease the number of bowel movements per day in patients with carcinoid syndrome diarrhea that cannot be managed with somatostatin analogues alone. The most common side effects are abdominal pain, fatigue, and increased gamma-glutamyl transferase level.

Etirinotecan Pegol

The CHMP delivered a negative opinion regarding etirinotecan pegol (Onzeald, Nektar Therapeutics). Onzeald was intended to be used to treat breast cancer with brain metastases.

The committee said that the agent's benefit had not been sufficiently demonstrated. "The claim of effectiveness relied on data from a subgroup of patients from a main study which, overall, failed to convincingly show the effectiveness of Onzeald," said the CHMP on its website.

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