PracticeUpdate Conference Series ASH 2018

Direct Oral Anticoagulants Safely Reduce Clotting Risk InOutpatient Cancer Setting But patient adherence was a problem in the trial.

A mbulatory cancer patients given rivaroxaban oral anticoagulation therapy are at a signifi- cantly lower risk of developing harmful clots while on treatment, according to results of the CASSINI trial. According to study presenter Alok Khorana, MD, of the Cleveland Clinic, the CASSINI study was designed to address an unmet need in clot preven- tion: Both chemotherapy and clots are more likely to occur in the outpatient setting, yet anticoagulant therapy is typically administered only in the hospi- tal setting and not prescribed for home use. The CASSINI trial is the first to investigate the use of oral anticoagulant therapy in ambulant can- cer patients at high-risk for clots. It was funded by Bayer, initial developers of rivaroxaban, and Janssen Pharmaceutica, the current marketers.

Previous studies investigated the use of heparin in the home setting to reduce risk of clotting in cancer patients; however, as Dr. Khorana suggested dur- ing a press briefing, the injection-based delivery and high cost of heparin make this therapy difficult to use from a patient adherence perspective. Dr. Khorana and his collaborators performed a randomized, double-blind, placebo-controlled, parallel-group, multicenter study, enrolling 1080 patients. Enrolled patients had various cancers and had venous thromboembolism (VTE) Khorana risk scores of 2 or higher. A screen for deep vein throm- bosis (DVT) eliminated 49 patients, and 190 were removed for other reasons, prior to randomization of the remainder (n=841), in which study participants were assigned 1:1 to a 180-day course of either daily oral rivaroxaban 10 mg or placebo. Of the 841 patients randomized, 32.6% had pancreatic cancer, 83% were white and 50.9% were male. The CASSINI trial failed to achieve statistical signifi- cance in its primary prespecified efficacy endpoint, a composite of objectively confirmed symptomatic or asymptomatic lower extremity or proximal DVT, symptomatic or incidental pulmonary embolism, and VTE-related death.

Dr. Alok Khorana

" …these findings could lead to a change in guidelines regarding primary prevention of VTE in cancer patients initiating systemic therapy. "

Ibrutinib-Based Therapy Beats Standard of Care as First-Line in Young Patients With CLL

P atients under the age of 70 with treatment-naive chronic lymphocytic leukemia (CLL) experience improved progression-free (PFS) and overall sur- vival (OS) outcomes when their first-line therapy is a combination of ibrutinib plus rituximab, rather than the standard of care chemoimmunotherapeutic regimen of fludarabine, cyclophosphamide, and rituximab (FCR), according to results of a phase III study presented at ASH 2018. Ibrutinib is a small molecule that binds permanently to Bruton’s tyrosine kinase. It has been approved by the United States FDA for the treatment of CLL since 2014. To test the performance of ibrutinib plus rituximab vs the standard of care head-to- head, researchers enrolled 529 patients (aged 28 to 70, median 57 years of age) who had previously untreated, symp- tomatic CLL and randomized them to

Outcomes and toxicity profile were superior with ibrutinib plus rituximab relative to FCR chemoimmunotherapy.

treatment with ibrutinib plus rituximab (n=354) or the FCR standard-of-care therapy (n=175). Patients were enrolled between January 2014 and June 2016. Ibrutinib plus rituximab was delivered at a dose of 420 mg/day of ibrutinib until dis- ease progression and rituximab 50 mg/m 2 on day 1 of cycle 2, 325 mg/m 2 on day 2 of cycle 2, and 500 mg/m 2 on day 1 of cycles 3 through 7. The FCR standard-of-care regimen involved 6coursesof intravenous fludarabine (25mg/ m 2 ) and cyclophosphamide (250mg/m 2 ) on days 1 through 3 with rituximab (50 mg/m 2 on day 1 of cycle 1, 325 mg/m 2 on day 2 of cycle 1, and 500 mg/m 2 on day 1 of cycles 2–6) over a 28-day period. After a median follow-up of 33.4 months, the hazard ratio for PFS, the prespecified primary endpoint, significantly favored therapy with ibrutinib plus rituximab over

Dr. Tait D. Shanafelt

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