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Evidence-Based Oncology January 2020

ASH 2019: Real-World Evidence and Cost of Care

Maggie L. Shaw and Mary Caffrey
Reviews of apixaban in active cancer, Medicare costs after CAR T-cell therapy, and the need for financial assistance for novel therapies.

Apixaban Is Linked to Large Reductions in Major Bleeding, Recurrent VTE in Active Cancer

Patients with cancer who took apixaban to prevent blood clots had a 37% reduction in major bleeding (MB) and a 39% reduction in recurrent venous thromboembolism (VTE) compared with those taking low-molecular weight heparin (LMWH), according to data presented on December 7, 2019, at the 61st American Society of Hematology Annual Meeting & Exposition in Orlando, Florida. Apixaban also had large reductions in VTE (32%) relative to warfarin.1

A subgroup analysis presented alongside the main study found that apixaban’s benefi ts relative to LMWH held up across different types of cancer regardless of the risk level they present for VTE.2 Apixaban is sold as Eliquis by Bristol-Myers Squibb/Pfizer. Patients with active cancer—for this study, defined as cancer diagnosis or treatment in the 6 months before or 30 days after a VTE diagnosis—have a 4 to 7 times greater risk of developing VTE.

To gain more real-world evidence on the eff ectiveness and safety of LMWH compared with vitamin K antagonists, which emerged in the last decade as a treatment of VTE, and non-VKA anticoagulants, a team of researchers led by Alexander T. Cohen, MBBS, MSc, MD, of King’s College, London, evaluated the effi cacy of apixaban, LMWH, and warfarin among patients with active cancer. 

The investigators examined 3 groups of patients who started treatment within 30 days of their first VTE: 3393 apixaban users, 6108 LMWH users, and 4585 warfarin users. The mean ages were 65, 64, and 64 years, respectively. To evaluate rates of MB, clinically relevant non-MB (CRNMB), and recurrent VTE, the patients were followed to the earliest of 1 of 6 time points: health plan disenrollment, death, index therapy discontinuation, switch to another anticoagulant, study end, or a maximum of 6 months.

The following results were reported: 

• Apixaban had lower risks of MB, CRNMB, and recurrent VTE compared with LMWH, with a hazard ratio (HR) of 0.63 (95% CI, 0.47-0.86; P = .003) for MB, an HR of 0.81 (95% CI, 0.70-0.94; P = .006) for CRNMB, and an HR of 0.61 for recurrent VTE (95% CI, 0.47-0.81; P = .001).

• Apixaban had lower rates of recurrent VTE and modest reductions of MB and CRNMB compared with warfarin, with an HR of 0.68 (95% CI, 0.52-0.90; P = .007) for recurrent VTE, an HR of 0.73 (95% CI, 0.53-1.0; P = 0.51) for MB, and an HR of 0.89 (95% CI, 0.77-1.04; P = 0.145) for CRNM. 

“Real-world evidence analyses such as this have the potential to provide additional insights into complex patient populations such as those with VTE and active cancer,” Cohen said in a statement.“Results from these analyses are a welcomed addition to the growing body of data around recurrent VTE in patients with active cancer.”

In the second presentation, results from the subgroup analysis examined how apixaban aff ected recurrent VTE, MB, and CRNMB risk across diff erent cancer types relative to warfarin and LMWN.  Hematologic cancer, as well as those of the brain, pancreas, stomach, liver, lungs, and kidneys, are associated with a higher risk of VTE. Researchers used the Khorana risk score based on cancer type, blood counts, and body mass index to evaluate risk level and assess the safety of each therapy based on cancer type. Patients were categorized as having a very high risk of VTE, high risk of VTE, or other.

Results from the same real-world data set as the fi rst abstract showed that those taking apixaban had a lower risk of recurrent VTE compared with warfarin and a lower risk of MB, CRNMB, and recurrent VTE compared with LMWH, consistent with the overall results. Researchers called for more studies to evaluate the role of anticoagulants in high-risk subgroups of patients with cancer who have VTE.2

Besides the risk of VTE, real-world evidence can be evaluated for other factors. Asked by Evidence-Based Oncology™ if the patient data could be evaluated to see whether those with comorbidities had diff erent responses, Danny Wiederker, HEOR team lead at Pfi zer, said in an email, “Comorbidities are always an important consideration in real-world evidence, given some may be important confounders that impact both the treatment decision and the outcomes of interest. That’s why the Pfizer/BMS Alliance leverages the best research practices recommended by organizations like the International Society of Pharmacoeconomics and Outcomes Research that look to adjust for both comorbidities and patient factors, like age, gender, etc, that may impact outcomes.” 

He said the study being presented is the inverse probability of treatment weighting to adjust for confounding while including the broadest possible patient population.

“Our approach generally is to start with the broad population and then drill down into subgroups as we are also highly interested in better understanding in which patient populations there is even more unmet need and more opportunity to improve outcomes,” Wiederker said. “We have conducted the first subgroup analysis presented as the second oral presentation stratifying based on the risk of recurrent VTE level, but we also have interest in other subgroups and are exploring opportunities for additional analyses.”


1. Cohen AT, Keshishian A, Lee T, et al. Safety and effectiveness of apixaban, LMWH, and warfarin among venous thromboembolism patients with active cancer: a retrospective analysis using four US claims databases. Presented at: 61st American Society of Hematology Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 326. Accessed December 7, 2019.

2. Cohen AT, Keshishian A, Lee T, et al. Safety and effectiveness of apixaban, LMWH and warfarin among venous thromboembolism (VTE) patients with active cancer: a subgroup analysis of VOTE risk scale. Presented at: 61 American Society of Hematology Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 327. Accessed December 7, 2019.

3. Findings released from real-world data analysis of Eliquis (apixaban) for the treatment of venous thromboembolism in patients with active cancer [press release]. Princeton, NJ, and New York, NY: Businesswire. Accessed December 7, 2019.


Real-World Results Show Medicare Costs Drop After Completion of CAR T-Cell Therapy

Most Medicare patients treated with chimeric antigen receptor (CAR) T-cell therapies in the first year after FDA approval for diff use large B-cell lymphoma fared well after the procedure, according to an Avalere Health study presented at the 61stŸAmerican Society of Hematology Annual Meeting and Exposition in Orlando, Florida.

More than half of the patients treated with this expensive revolutionary therapy had comorbidities common in seniors, such as heart disease or renal problems, that might have kept them out of clinical trials. But 6 months after treatment, hospital stays dropped 17% from pretreatment levels. And healthcare costs 6 months after CAR T-cell therapy, based on Medicare Part A and B, were 39% lower than they were in the 6 months before treatment, said lead study author Karl M. Kilgore, PhD, who shared results from 207 patients in a press briefi ng on December 7, 2019. The study is the first claims analysis from Medicare patients who received CAR T-cell therapy in the year after October 1, 2017.1 The FDA approved Novartis’ tisagenlecleucel (Kymriah) in August, followed by Gilead’s axicabtagene ciloleucel (Yescarta), in October 2017. Both are approved to treat adults with relapsed or refractory large B-cell lymphoma.2

Medicare patients in the Avalere study were more than a decade older than the median age of patients in clinical trials, yet many had good outcomes. “Our findings off er evidence that older patients with multiple comorbidities can be treated successfully with CAR T,” he said in a statement.3 “While we don’t know the long-term outcomes yet, nearly three-quarters of the patients were still alive 6 months posttreatment.”

Kilgore said this is the fi rst analysis to use real-world evidence—in this case, Medicare claims—to examine how CAR T-cell therapy works in older patients with other health issues. Although the Avalere study found a signifi cant decline in both healthcare utilization and cost, Kilgore was clear that this “is not a cost-effectiveness study,” meaning it was not designed to evaluate the healthcare savings seen after treatment against the cost and benefits of treatment itself. CAR T-cell therapy in this indication costs $373,000 just for the specially engineered therapy manufactured from a patient’s own cells. Administration costs, including the cost of treating adverse events, can easily drive the total price tag closer to $1 million.

Medicare and academic centers that off er CAR T-cell therapy have battled over reimbursement rates for more than a year, and while payment is set to rise in 2020, a commentary in the Journal of Clinical Oncology in November estimated that centers lose $300,000 on every Medicare patient they treat.4

Highlights from the Avalere study showed1:

• The median age of the Medicare patients was 71, compared with 56 to 58 years of age in clinical trials, and 51% of individuals in the Medicare group had 1 or more

chronic conditions.

• Results after 177 patients showed the drop in per-patient per-month healthcare utilization costs in Medicare Part A and B fell from $9749 in the period 6 months before CAR T-cell therapy to $7121 in the 6 months after therapy. Kilgore said in an interview with Evidence-Based Oncology™ that Part D data had not been released in time for the American Society of Hematology meeting and would be analyzed separately.

• Six months after treatment, emergency department visits dropped by 45%, and the number of patients visiting the emergency department dropped by one-third.

• The study shed light on the healthcare needs of Medicare patients receiving CAR T-cell therapy—the average hospital stay for the procedure is 17 days. Less than half needed time in the intensive care unit; those that did stayed 13 days.

Kilgore noted that reimbursement methods to hospitals performing CAR T-cell treatment vary, with some subject to the acute inpatient prospective payment system rule, while others are exempt.5 The Avalere study found that the Centers for Medicare & Medicaid Services, on average, is reimbursing under the inpatient prospective payment system about $422,000, compared with $467,000 in the outpatient setting.3

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