FDA Approves New Oral Drug for Treatment of Patients With Certain Blood Cancers

The US Food and Drug Administration (FDA) has approved duvelisib (Copiktra; Verastem) for the treatment of adults with relapsed or refractory chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), or small lymphocytic lymphoma (SLL) who have received 2 or more previous therapies. Duvelisib was approved under the FDA's priority review, and the indication for use in patients with FL received accelerated approval.

The approval of this oral inhibitor of phosphoinositide 3-kinase (PI3K) for these indications marks the first authorization of a dual inhibitor of PI3K-delta and PI3K-gamma.

"COPIKTRA is a significant addition to physicians' treatment armamentarium that I believe will address an unmet need for patients who have limited options once they have progressed after two prior therapies,” Ian W. Flinn, MD, PhD, Director, Lymphoma Research Program, Sarah Cannon Research Institute, Nashville, TN, said in a press statement by Verastem (September 2018).

The FDA approval of duvelisib for CLL and SLL was based on a multi-center, open-label clinical trial that compared duvelisib with ofatumumab in patients with relapsed or refractory CLL or SLL. Patients were randomized in a 1:1 ratio to receive oral duvelisib 25 mg twice daily or intravenous ofatumumab (administered intravenously at 300 mg for 1 week, followed by 2000 mg once weekly for 7 doses, and then 2000 mg once every 4 weeks for 4 additional doses).

Among 196 previously treated patients, the estimated median progression-free survival was 16.4 months with duvelisib (n = 95) versus 9.1 months with ofatumumab (n = 101). The overall response rates (ORR) were 78% and 39% for the duvelisib and ofatumumab arms, respectively.

The FDA approval of duvelisib for FL was based on a single-arm, multi-center clinical trial of 83 patients with FL who were refractory to rituximab and chemotherapy or radioimmunotherapy. The ORR was 42%, with 41% of patients experiencing partial responses and 1 having a complete response. Of the 35 patients who responded to treatment with duvelisib, 15 (43%) maintained responses for at least 6 months, and 6 (17%) for at least 12 months.

Per the FDA, continued approval of duvelisib for the FL indication may be contingent upon verification of clinical benefit demonstrated in a scheduled randomized trial.

The most common (incidence 20% or higher) adverse reactions with duvelisib were diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia. The prescribing information for duvelisib includes black box warnings for fatal and/or serious infections, diarrhea or colitis, cutaneous reactions, pneumonitis, neutropenia, and hepatotoxicity.—Hina Khaliq