San Diego, CA—A study examining the feasibility and applicability of the American Society of Clinical Oncology (ASCO) Value Framework in chronic lymphocytic leukemia (CLL) suggests that the tool, although useful in assessing a small percentage of drug regimens, may need to be amended to be useful in CLL, reported Erlene K. Seymour, MD, Assistant Professor, Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, at the 2016 American Society of Hematology meeting.
“The ASCO Value Framework is a promising tool that helps compare cost and net health benefits, but there are major limitations when applied to CLL. These include a limited number of trials that could be evaluated by the framework and a lack of trials comparing stronger control arms,” Dr Seymour said.
“To optimize application of this framework, we would urge investigators and sponsors to consider the assessment and reporting of the required variables to determine the net health benefit of therapies in clinical trials,” he added.
The ASCO Value Framework was developed to assist in value assessments of cancer drugs, including efficacy, toxicity, and cost, but data on its feasibility and clinical application have not been widely reported.
Dr Seymour and co-investigator, Jonas A. de Souza, MD, MBA, Assistant Professor of Medicine, Section of Hematology/Oncology, University of Chicago, IL, used the ASCO Value Framework to compare the net health benefit and cost for all the regimens listed in the National Comprehensive Cancer Network (NCCN) guidelines for CLL.
“We chose to evaluate CLL because standard of care for this disease has changed dramatically in the last 5 years with the introduction of new targeted therapies,” said Dr Seymour.
Using the NCCN guidelines, the researchers reviewed the regimens for CLL in the frontline and relapsed or refractory settings. The studies that included these regimens were then screened for possible evaluation with the ASCO Value Framework, which is limited to prospective, randomized controlled clinical trials. An additional randomized, prospective clinical trial that was mentioned in the guidelines, but not yet listed as a reference, was also included in this assessment.
After screening 39 potential studies, the researchers determined that only 8 could be evaluated by the ASCO Value Framework. Although the framework was able to demonstrate clinical benefit over cost in some situations (Table), the net health benefit scores of various treatment regimens were often inflated because of the tendency of randomized, prospective studies to use less potent control arms, said Dr Seymour.
“In clinical practice, the real question is whether ibrutinib [Imbruvica] is better than chemotherapy,” said Dr Seymour. “I’m not giving patients the option of chlorambucil as their second choice, because we already know that it isn’t a great drug by itself, but a net health benefit score based on that comparison will be high. To really optimize this tool, we need a trial comparing ibrutinib to chemotherapy regimens.”
In addition, the researchers recommended placing more weight on certain toxicities, such as infections, to appreciate clinical differences.
“The problem with the present methodology is that it’s still arbitrarily weighing grade 3 and 4 toxicities; it’s not paying attention to toxicities that are more clinically relevant,” said Dr Seymour. For example, grade 3 or 4 diarrhea is given equal value as grade 3 or 4 opportunistic infection. However, because CLL regimens are more myelosuppressive, approximately 50% of patients die from infection.
“Certain toxicities matter more than others, even within the grade 3 to 4 category. Opportunistic infection has much greater importance because it affects cancer-related mortality,” she said.
Drs Seymour and de Souza also advocated for uniform reporting of clinical variables used to calculate clinical benefit scores.
“If you have the hazard ratio for overall survival in one trial and the hazard ratio for progression-free survival in another trial, they’re not great comparators. Most trials will have all those variables, but they’re just not uniformly reported,” said Dr Seymour.
Finally, a cost comparison showed that new oral therapies, which are used for the long-term, have the highest cost-sharing. Although chemoimmunotherapy is less costly for patients, it has the highest drug-acquisition cost.
A direct comparison of ibrutinib versus chemoimmunotherapy is needed in clinical practice, given the large cost difference, said Dr Seymour, emphasizing that having these net health benefit scores would aid in clinical decision-making.