|In the first quarter of 2014, several drugs have already received approval by the US Food and Drug Administration (FDA) as new therapies, new combinations, or new indications for patients with different types of cancer, including solid tumors and hematologic malignancies. The following briefs provide updates on new FDA approvals and indications to help hematology and oncology pharmacists keep up with new information regarding drugs that are coming to market for the management of patients with cancer. This section also provides brief updates on the FDA’s decisions for drugs in the pipeline before the final approval.|
First Drug Combination Approved for Unresectable or Metastatic Melanoma
On January 8, 2014, the FDA approved the use of dabrafenib (Tafinlar; GlaxoSmithKline) plus trametinib (Mekinist; GlaxoSmithKline) as a new combination therapy for the treatment of patients with advanced melanoma that is unresectable or metastatic. The 2 drugs were individually approved by the FDA in 2013 for melanoma. Each of the 2 drugs blocks molecular signaling in different sites of the same pathway that promotes cancer-cell growth. Dabrafenib was initially approved for patients with melanoma whose tumors express the BRAF V600E mutation. The dabrafenib-trametinib combination is indicated for patients with melanoma who also have the BRAF V600E or BRAF V600K mutation. Approximately 50% of skin melanomas have a BRAF mutation.
“Mekinist and Tafinlar are the first drugs approved for combination treatment of melanoma,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Their development for combination use is based on the strong understanding of the biological pathways of the disease. This approval illustrates the value of continuing to study drugs in combination for clinical development.”
The FDA approval was based on results of a clinical trial of 162 patients with unresectable or metastatic melanoma with the BRAF V600E or BRAF V600K mutation; the majority of the patients were treatment-naïve. They received dabrafenib as a single agent until their disease progressed or their side effects became intolerable, at which point they began using the combination. Overall, 76% of patients receiving the combination had an objective response for an average of 10.5 months compared with 54% of patients receiving dabrafenib alone who had an objective response lasting 5.6 months. Clinical trials are ongoing to determine whether this combination will also result in improved survival.
The side effects reported with the combination are similar to those reported with each individual drug. Specifically, the combination was associated with an increase in the incidence and severity of fever.
Ibrutinib Receives New Indication for Use in Patients with Chronic Lymphocytic Leukemia
On January 12, 2014, the FDA approved a new indication for ibrutinib (Imbruvica; Pharmacyclics) for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least 1 previous therapy. The approval was granted under the FDA’s accelerated approval process to expedite access to patients with CLL to this promising new medication. Ibrutinib also received an orphan drug designation by the FDA.
On November 13, 2013, the FDA granted accelerated approval to ibrutinib for the treatment of patients with mantle-cell lymphoma, a rare and aggressive type of hematologic cancer; this approval, too, was for patients who had received at least 1 previous therapy.
“Today’s approval provides an important new treatment option for CLL patients whose cancer has progressed despite having undergone previous therapy,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “The FDA completed its review of Imbruvica’s new indication under the agency’s accelerated approval process, which played a vital role in rapidly making this new therapy available to those who need it most,” Dr Pazdur said.
The new FDA indication for ibrutinib for CLL is based on the results of a clinical trial with 48 previously treated patients with CLL. Patients were diagnosed with CLL, on average, 6.7 years before enrolling in the study and had received 4 previous therapies. Patients received oral ibrutinib until disease progression or unacceptable toxicity. Overall response was seen in nearly 58% of the patients, with a response duration of 5.6 months to 24.2 months during the study. Improve-ments in survival or disease-related symptoms have not been established.
The most common side effects reported with ibrutinib include thrombocytopenia, diarrhea, bruising, neutropenia, anemia, upper respiratory tract infection, fatigue, musculoskeletal pain, rash, pyrexia, constipation, peripheral edema, arthralgia, nausea, mouth sores, sinusitis, and dizziness.