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Copanlisib Plus Rituximab Shows Superior Efficacy Over Monotherapy in FL, MZL
Copanlisib when given in combination with rituximab demonstrated superior efficacy when compared to rituximab monotherapy in patients with relapsed follicular lymphoma (FL)/marginal zone lymphoma (MZL), according to study findings presented at the virtual 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.
Rituximab monotherapy is an already approved treatment for patients with relapsed indolent non-Hodgkin’s lymphoma (iNHL) who have a prolonged progression- and treatment-free interval after their last rituximab-based therapy or who are unable to receive chemotherapy. Copanlisib is a PI3K inhibitor approved as a monotherapy for patients with relapsed FL who have progressed after ≥2 systemic therapies.
Thus, Matthew J. Matasar, MD, and colleagues, developed the phase III CHRONOS-3 study to determine the safety and efficacy of copanlisib plus rituximab compared to placebo plus rituximab in patients with relapsed iNHL.
A total of 458 patients (median age 62) with iNHL who were progression- and treatment-free for ≥12 months after their last rituximab-based therapy or ≥6 months if unable to receive chemotherapy were identified from a dataset as of August 31, 2020 and enrolled in the study. Of that, 250 patients with FL/MZL (184 FL/66 MZL) were randomized to receive copanlisib and rituximab and 120 (91 FL/29 MZL) received placebo and rituximab.
The primary endpoint was centrally assessed progression-free survival (PFS) by Cheson 2014 criteria. Secondary endpoints included objective response rate (ORR), duration of response (DoR), complete remission rate (CRR), time to progression (TTP), and treatment-emergent adverse events (TEAEs). All patients were assessed for efficacy, and patients were assessed for safety if they received ≥1 dose of copanlisib/placebo or rituximab.
At median follow-up of 18.5 months, copanlisib plus rituximab significantly reduced the risk of disease progression and death compared to placebo and rituximab (hazard ratio [HR], 0.55; 95% CI, 0.40-0.76; P=.0001). The median PFS was 22.2 months (95% CI, 19.1-33.1) versus 15.4 months (95% CI, 11-19.2), respectively. The median TTP was 27.5 months for copanlisib and rituximab compared with 15.4 months for placebo and rituximab (HR, 0.500; P=.00001). The ORRs were 82.4% (CRR 37.65) for copanlisib and rituximab and 50.8% (CRR 18.3%) for placebo and rituximab. The median DoR was 23.9 months versus 17.9 months, respectively.
The most common adverse events of all grades in patients with FL/MZL receiving C+R (n=249) were hyperglycemia (72.7%), hypertension (53.8%), and diarrhea (35.3%). For patients receiving P+R (n=116), the most common were hyperglycemia (23.3%), hypertension (19.8%), neutropenia (18.1%), and upper respiratory tract infection (18.1%).
Researchers concluded that copanlisib and rituximab demonstrated superior efficacy over rituximab monotherapy.
“Copanlisib is the first PI3K inhibitor to be safely combined with rituximab in relapsed FL/MZL, representing a potential new therapeutic option,” reported Matasar and colleagues.—Emily Bader
Matasar MJ, Capra M, Özcan M, et al. Copanlisib + rituximab versus rituximab + placebo in patients with relapsed follicular (FL) or marginal zone lymphoma (MZL): Subset analysis from the phase III CHRONOS-3 trial. Presented at: the 2021 ASCO Annual Meeting; June 4-8, 2021; virtual. Abstract 7510.
