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FDA Approvals for Revlimid for MCL and Xgeva for Giant Cell Tumor of the Bone

doi: 10.1097/01.COT.0000432329.52353.a9

The U.S. Food and Drug Administration has approved the use of lenalidomide capsules (Revlimid, Celgene Corporation) to treat patients with relapsed mantle cell lymphoma (MCL), as well as for patients with disease that has progressed after two prior therapies, one of which included bortezomib. The agency also expanded the approved use of Xgeva (denosumab) to treat adult patients and some adolescent patients with giant cell tumor of the bone (GCTB).

Revlimid's approval is based on a single-arm, multicenter trial of 134 patients with MCL who had relapsed after or were refractory to bortezomib or a bortezomib-containing regimen (all patients had received prior treatment with bortezomib). Out of 133 patients who were evaluable for efficacy: 26 percent had an overall response; seven percent achieved a complete response or an unconfirmed complete response; and 19 percent had a partial response. The median duration of response for these three groups of patients was 16.6 months.

Safety data were evaluated in all 134 patients who had received at least one Revlimid dose. The median duration of therapy was 95 days, during which 78 patients received three or more cycles of therapy.

Of the patients on the trial: 76 had at least one dose interruption due to adverse events; 51 patients had at least one dose reduction due to adverse events; and 26 discontinued treatment due to adverse events.

The most common grade 1-4 adverse events were neutropenia, thrombocytopenia, fatigue, anemia, nausea, pyrexia, rash, dyspnea, pruritus, constipation, peripheral edema, and leukopenia. The most common grade 3-4 adverse reactions were neutropenia, thrombocytopenia, anemia, pneumonia, leukopenia, fatigue, febrile neutropenia, dyspnea, pruritus, and diarrhea.

In 2005 Revlimid received approval for the treatment of patients with myelodysplastic syndrome with the cytogenetic abnormality 5q-deletion and transfusion-dependent anemia. And since then, trials have evaluated the drug in other hematologic malignancies used as a single agent and in combination with other drugs (OT, 5/10/13 issue).



The recommended dose and schedule for oral Revlimid for MCL is 25 milligrams taken once daily on days one through 21 of repeated 28-day cycles. This supplemental application also included the approval of a new 20 milligram capsule strength.

The new approval for Xgeva, a monoclonal antibody that binds to the protein RANKL, is intended for patients with unresectable GCTB or in cases when surgery is likely to result in severe morbidity to the patient. In adolescents, the drug is intended only for patients whose bones have matured.

“The approval of Xgeva provides a needed treatment option for patients with GCTB who are not surgical candidates or who would otherwise have to undergo extensive, life-altering surgery,” said Richard Pazdur, MD, Director of the FDA's Office of Hematology and Oncology Products in the Center for Drug Evaluation and Research.

Xgeva was reviewed under the FDA's priority review program, which provides for an expedited six-month review for drugs that may provide safe and effective therapy when no satisfactory alternative therapy exists, or offer significant improvement compared to marketed products. Xgeva was granted orphan product designation because it is intended to treat a rare disease or condition.

The safety and effectiveness of Xgeva for this indication were established in two clinical trials that enrolled 305 adult or adolescent patients with confirmed cases of GCTB that were recurrent, unresectable or where surgery would result in severe morbidity. Of 187 patients whose tumors could be measured, 47 patients had their tumors reduce in size after an average of three months. Over an average follow-up duration of 20 months, re-growth of GCTB occurred in three patients whose tumors originally became smaller during treatment.

Common side effects included arthralgia, headache, nausea, fatigue, back pain, and extremity pain. The most common serious side effects were osteonecrosis of the jaw and osteomyelitis. Women of reproductive potential should use highly effective contraception while taking Xgeva because of potential fetal harm.

Xgeva, marketed by Amgen, was approved in 2010 to prevent fractures when cancer has spread to the bones. It is marketed by Amgen.

© 2013 by Lippincott Williams & Wilkins, Inc.
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