EMA Panel Makes Oncology Product Announcements - Medscape

The European Medicines Agency's (EMA's) Committee for Medicinal Products for Human Use (CHMP) was busy this month with oncology drugs and agents, making a host of recommendations and announcements at its October meeting.

CHMP recommended granting a conditional marketing authorization for the oral agent venetoclax (Venclyxto, AbbieVie) for the treatment of adults with chronic lymphocytic leukaemia (CLL). Venetoclax acts by inhibiting B-cell lymphoma–2 (BCL-2), an antiapoptotic protein that is overexpressed by B-cells in CLL and thus induces tumor cell apoptosis.

The full indication is complex. Venetoclax monotherapy is indicated for the treatment of CLL in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor. Venetoclax monotherapy is also indicated for the treatment of CLL in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

In single-arm studies, venetoclax produced responses in patients unsuitable for or refractory to B-cell receptor pathway inhibitors and other anticancer medicines.

For example, in a pivotal phase 2 trial conducted in 107 CLL patients who harbored the 17p deletion and whose prognoses were poor, the new drug achieved an overall response rate of 79.4%. Response was maintained in most patients (84.7%) 1 year later. "This is a very special population with the most dismal outcome," said lead author Stephan Stilgenbauer, MD, of the University of Ulm, Germany, at last year's annual meeting of the American Society of Hematology (ASH), where the study was presented, as reported by Medscape Medical News.

The most common side effects are neutropenia/decreased neutrophil count, diarrhea, nausea, anemia, upper respiratory tract infection, fatigue, hyperphosphataemia, vomiting, and constipation.

CHMP also recommended granting a marketing authorization for edotreotide (SomaKit-TOC) for the diagnosis of gastro-entero-pancreatic neuroendrocrine tumors in adult patients using positron emission tomography imaging. Edotreotide detects tumors that overexpress somatostatin receptors. No adverse reactions related to edotreotide have been reported; however, exposure to ionizing radiation is a potential risk, as with other radiopharmaceuticals, said the EMA in a press statement.

CHMP recommended extending the therapeutic indication of nivolumab (Opdivo, Bristol-Myers Squibb) to include the treatment of adult patients with relapsed or refractory classical Hodgkin's lymphoma after autologous stem cell transplant and treatment with brentuximab vedotin (Adcetris, Seattle Genetics). Nivolumab was previously approved for the treatment of melanoma, non–small cell lung cancer, and renal cell carcinoma.

CHMP recommended a change to the terms of the marketing authorization for arsenic trioxide (Trisenox, Teva). The agent is now recommended for induction of remission and for consolidation in adult patients with newly diagnosed low- to intermediate-risk acute promyelocytic leukemia (APL) (white blood cell count ≤ 10 x 103/μl) in combination with all-trans-retinoic acid (ATRA). The same recommendation has been made for relapsed/refractory APL when previous treatment included a retinoid and chemotherapy. In both cases, these clinical scenarios are characterized by the presence of the t(15;17) translocation and/or the presence of the pro-myelocytic leukemia/retinoic-acid-receptor-alpha (PML/RAR-alpha) gene. Previous treatment should have included a retinoid and chemotherapy.

CHMP also announced oncology-related withdrawals of applications. AstraZeneca withdrew its application for a marketing authorization for cediranib (Zemfirza), an antivascular endothelial growth factor (VEGF) receptor agent, for the treatment of ovarian cancer. Hospira UK withdrew its application for a marketing authorization for ditromethamine (generic pemetrexed) for the treatment of malignant pleural mesothelioma and non–small cell lung cancer.

Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick.

For more from Medscape Oncology, follow us on Twitter: @MedscapeOnc.