Oral targeted therapies, such as ibrutinib (Imbruvica) and idelalisib (Zydelig), represent a major advance for patients with chronic lymphocytic leukemia (CLL) and have undoubtedly changed the treatment paradigm for this disease and the clinical outcomes.
However, with the average treatment cost expected to rise by 75% per patient by 2017, these drugs also represent a significant economic burden for patients and for payers, said Nitin Jain, MD, Assistant Professor of Medicine, Department of Leukemia, M.D. Anderson Cancer Center, Houston, at ASH 2015.
“Targeted therapies are expected to bring about new challenges related to financial toxicity, including decreased adherence and limited access due to high copays,” he said. “Therefore, a more tolerable and sustainable pricing for such therapies is urgently needed.”
According to Dr Jain, there has been a major transformation in CLL therapies in the past few years. Two phase 3 clinical trials led to the approval of ibrutinib and idelalisib (in combination with rituximab) for patients with relapsed CLL in 2014.
Before 2014, no targeted therapies had been approved by the FDA for CLL, said Dr Jain. “Now ibrutinib and idelalisib are recommended for therapy in the relapsed setting.”
Gains in long-term survival, however, have come with a dramatic increase in cost.
The triple-drug regimen of fludarabine, cyclophosphamide, and rituximab (FCR) is considered standard of care for younger patients with CLL in the frontline setting, and is typically given for 6 cycles, amounting to $50,000 to $60,000 for 1 course of treatment.
Obinutuzumab plus chlorambucil, another common regimen, is approved for all other patients with CLL who have comorbidities. This regimen also costs approximately $50,000 for 1 course of treatment, Dr Jain said.
By contrast, ibrutinib and idelalisib are priced at >$100,000 annually ($10,000-$11,000 monthly).
“Unlike other regimens of set duration,” said Dr Jain, “it’s important to mention that these drugs are recommended to be taken lifelong until disease progression.”
Dr Jain noted that a phase 3 study reported at the meeting will likely lead to the approval of ibrutinib in the frontline setting, perhaps as early as 2016.
“Once that happens,” he said, “a majority of patients will receive ibrutinib or other targeted therapies in the frontline setting and chemotherapy, such as FCR, in the salvage setting.”
Total Cost of Management Rising
Using a Markov model, Dr Jain and colleagues compared 2 management strategies—oral targeted therapy and chemoimmunotherapy. The outcomes included the annual prevalence of CLL, the annual cost of CLL care, and the lifetime cost for a patient with CLL.
The estimation of the cost incorporated the drug cost (average wholesale price, based on dose and unit price of each drug), the administration cost of chemoimmunotherapy (there was no administration cost for oral targeted therapies), the cost of treating grade 3 or 4 adverse events, and the cost of follow-up care.
As a result of significantly better progression-free survival and overall survival with oral targeted therapies compared with chemoimmunotherapy, the number of CLL survivors is expected to rise to >200,000 patients by the year 2025.
“With oral targeted therapies, cost will rise from just over $1 billion to upwards of $6 billion by the year 2025,” said Dr Jain. “When these drugs get approved in the frontline setting, the majority of the cost will be driven by the use of oral targeted agents in the frontline setting.”
Finally, based on this analysis, the average lifetime treatment cost per patient is expected to increase from approximately $400,000 in 2015 to $700,000 after 2017. Although this cost increase is associated with significant improvements in patient outcomes, the cost-effectiveness of these improvements is worth considering, Dr Jain said.