A phase II trial of the pan-class I PI3K inhibitor copanlisib demonstrated that it induces objective responses in 59% of patients with relapsed or refractory indolent lymphoma. The responses lasted a median of 22.6 months. Although the drugs weren't compared head to head, researchers suspect that the side effects of copanlisib may be less severe than those of idelalisib, another PI3K inhibitor.

Copanlisib (Aliqopa; Bayer) is effective and may be a safer option for patients with relapsed or refractory indolent lymphoma than related drugs, a phase II study suggests.

Patients with indolent B-cell lymphoma who progress on first-line and second-line therapy may receive the PI3K inhibitor idelalisib (Zydelig; Gilead Sciences), which blocks the PI3Kδ isoform. Last year, however, six lymphoma and leukemia trials involving the drug were halted because of its side effects, which can include colitis, pneumonitis, liver toxicity, and intestinal perforation. In early-phase trials, researchers found that the pan-class I PI3K inhibitor copanlisib seemed to cause less severe types of side effects.

To assess the drug, Martin Dreyling, MD, PhD, of Ludwig Maximilians University of Munich in Germany, and colleagues launched the CHRONOS-1 trial, which included 142 patients with relapsed or refractory indolent lymphoma who had already tried at least two therapies. The patients, most of whom had follicular lymphoma or marginal zone lymphoma, received infusions of copanlisib three times per month until their cancer progressed or they could no longer tolerate the drug's side effects.

After a median of 22 weeks of treatment, the objective response rate was 59%, with 12% of the patients showing a complete response. The median response duration was 22.6 months, and the median progression-free survival was 11.2 months. The median overall survival has not been reached.

The most common serious side effect was transient hyperglycemia, which occurred in half of the patients. In addition, 30% of the patients developed transient hypertension. Other, less frequent serious side effects included diarrhea, fatigue, and noninfectious pneumonia. Although the study didn't include a control arm, hepatic transaminitis, diarrhea, colitis, and colon perforations were much less common than reported in earlier studies of idelalisib, notes Dreyling. Only one patient receiving copanlisib developed colitis, and none experienced colon perforation.

Idelalisib is an oral drug, whereas patients receive copanlisib intravenously. “Initially, we assumed this was a disadvantage, but at least when it came to toxicity, this was an advantage,” says Dreyling. Copanlisib's delivery route might have helped reduce the severity of gastrointestinal side effects, he says.

“These data do support the use of this agent and further support the efficacy of this class of drugs,” says Ajay Gopal, MD, of the University of Washington in Seattle, who wasn't connected to the study. “The different side-effect profile than idelalisib and the IV route of administration give patients and MDs choices with these agents.”

Jonathan Friedberg, MD, of the Wilmot Cancer Institute at the University of Rochester Medical Center, NY, adds that “this is another example of the utility of blocking PI3 kinase in the treatment of indolent lymphoma.” Copanlisib “gives us an expanded range of options for patients with relapsed disease.”

Copanlisib has now been approved for patients with relapsed follicular lymphoma who have received at least two systemic treatments. Other studies are investigating its effectiveness in combination with other drugs in earlier lines of therapy. Two trials are testing copanlisib with various permutations of rituximab and chemotherapy in patients with relapsed indolent non-Hodgkin lymphoma. Dreyling and colleagues also plan to launch a phase II trial of copanlisib as a first-line treatment. –Mitch Leslie

©2017 American Association for Cancer Research.
2017
American Association for Cancer Research.