Top Takeaways from ASH: Oral anticoagulants shift cancer-related thrombosis treatment paradigm

With a range of questions lingering unanswered in the arena of cancer-related thrombosis, new research presented at the ASH Annual Meeting and Exposition armed clinicians with relevant data to help guide patient care.

Alok A. Khorana, MD, Vice-Chair for Clinical Services of the Taussig Cancer Institute and Director of the Gastrointestinal Malignancies Program at the Cleveland Clinic, offers takeaways on results surrounding knowledge gaps in treatment.

Alok A.
Khorana

Drug dilemmas

Although findings from two large clinical trials, CLOT and CATCH, have served as grounds for consensus that all patients with cancer and thrombosis should receive extended low–molecular-weight heparin therapy — daily self-injections over 6 months — FDA approvals for several direct oral anticoagulants have created uncertainty, Khorana explained.

“The challenge is that none of the newer drugs have done head-to-head comparisons with LMWH,” he said. “They’ve done it all vs. warfarin, which we know is inferior to LMWH.”

The agents in this category now available for use are rivaroxaban (Xarelto, Janssen Pharmaceuticals), edoxaban (Savaysa, Daiichi Sankyo), apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) and dabigatran (Pradaxa, Boehringer Ingelheim), according to Khorana.

“Here is this whole generation of drugs that are easy to use — one-a-day pills, no monitoring required — and it’s frustrating because we keep having to prescribe these injections to patients who are already going through so much grief for their cancer,” he said.

Dissecting the data

Researchers at Memorial Sloan Kettering Cancer Center in New York presented promising results from a clinical pathway, established under a quality assurance initiative, to guide the use of the oral direct factor Xa inhibitor rivaroxaban for cancer-associated thrombosis.

“They’ve been using the rivaroxaban as their anticoagulant of choice for the last year and a half,” Khorana said. “They found the recurrence of clots and bleeding were very comparable to what we see with LMWH.”

The study population included patients with solid tumors and hematologic malignancies at all stages of cancer. Guidelines for the clinical pathway — including dosing in the setting of thrombocytopenia, older age, and transient renal or hepatic dysfunction — would be available upon request pending publication, according to the researchers.

“Patients are offered the choice between LMWH and rivaroxaban, and basically 99% choose the oral agent,” he said. “There is a clear patient preference for the new oral agents. There doesn’t seem to be any red flags in terms of higher recurrence rates or higher bleeding rates.”

Khorana also pointed to a retrospective chart review of patients at H. Lee Moffitt Cancer Center in Tampa, Fla., demonstrating similar rates of deep venous thrombosis and pulmonary embolism with rivaroxaban vs. the LMWH dalteparin (Fragmin, Pfizer).

In this study population of patients with predominantly active cancer and comorbidities including hypertension, diabetes and coronary artery disease similar between groups, the findings suggest both efficacy and safety of the new anticoagulant.

“These researchers also showed that the new oral agents are acceptable to use in the cancer population,” Khorana said.

Additionally, he highlighted an investigation into treatment choices once maximum LMWH duration is reached from the Computerized Registry of Patients with Venous Thromboembolism (RIETE) — a multidisciplinary project designed to help physicians understand thromboembolic disease, particularly in subgroups not usually recruited in randomized clinical trials.

The international team of researchers found that in patients with cancer-associated thrombosis who finish 6 months of anticoagulation with LMWH, switching to warfarin does not increase recurrent VTE, major bleeding or total bleeding compared with continuing LMWH.

“This study looked at what to do after the duration of anticoagulation that we typically do now,” Khorana said. “All the studies that have looked at this have shown you could transition to an oral agent after six months, and patients seem to do fine.”

Lastly, Khorana offered investigator insight into current prescription patterns and patient persistence on anticoagulant therapy for cancer-associated thrombosis.

Through an analysis of medical and pharmacy claims from the Humana Database, the researchers determined that despite guidelines recommendations for LMWH, only a quarter of patients actually get LMWH and the remainder get warfarin and rivaroxaban.

“I believe patients and physicians are making choices already, even though the full data are not there yet. We want to get that data.”

Randomized trials are now ongoing to help confirm the agents are “ready for prime time,” said Khorana, highlighting studies in Europe and North America comparing each of the new oral anticoagulants vs. LMWH.

“Those data should be out over the next couple of years,” he said. “But for right now it appears, at least in select patients, that we can safely start using the direct oral agents.”

Disclosure: Khorana reports receiving honoraria from Bayer, Daiichi Sankyo, Halozyme, Janssen, Leo Pharma, Pfizer, Roche and Sanofi.

References:

Chai-Adisaksopha C, et al. Abstract 430. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.

Chaudhury A, et al. Abstract 432. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.

Khorana AA, et al. Abstract 626. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.

Mantha S, et al. Abstract 431. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.