Created by a panel of experts, the Evidence Blocks incorporate “the acquisition cost of the agent, required supportive therapy, the likelihood and expense of managing adverse events (AEs), and site of care, among other factors.” Carlson and McClure said the affordability metric does not specifically weigh costs versus benefits or costs versus toxicity; however, they said the Evidence Blocks have high utility for considering multiple measures of value at one time, including “efficacy, safety, data quality, data consistency, and affordability.”
The SITC group also aims to determine whether alternative means are possible for compensating manufacturers for their research and development costs; the current system incorporates these expenses into the drug price. There’s also a concern that the true AE profiles of these newer drugs may not be as mild as they appear, and Kaufman said his group would like to see more exploration of this issue. For example, the results of a study presented at the European Society of Medical Oncology 2016 Congress suggested that clinical trials of I/O drugs often fail to report treatment-related AEs. The researchers gave low marks to 90% of 81 separate trials of targeted and I/O drugs for the quality of reporting of the duration of AEs and recurrent or late toxicities. The trials were of therapies approved by the FDA between 2000 and 2015. “With some of these therapies, the toxicity might not be as low as we think it is,” Kaufman said. “We do have to compile longer-term follow-up data. If you think about it, some of these drugs are pretty new. When do you use PD-L1 versus PD-1? It looks like some of these agents might have long-term toxicities.” More long-term data would help to clear this up, he said.
The Duration of Treatment Could Be Shortened
Similarly, more information is needed to determine how long patients need to stay on I/O drugs. Kaufman said oncologists are learning that with some of these drugs, the indicated duration of treatment may be much longer than necessary, meaning that additional savings could be realized by shortening the duration of treatment. In addition, combination therapies involving I/O drugs offer savings that should be incorporated into valuation models. This is because patients on combination therapy may receive smaller doses of particular drugs than those on single-drug regimens. “There are some interesting parameters that one could use as a basis to develop regimens that make more sense. The combinations may be much more effective. They may actually be cheaper, but then the toxicity question comes in,” Kaufman said.
Carlson and McClure say that a lot of these questions eventually will be answered. “Over time and with more experience with these agents, all stakeholders will gain a better understanding of the efficacy of these agents and which patients are most likely to benefit. Clinicians will also gain expertise in recognition and management of toxicities which will allow them to be addressed in a timely manner with appropriate therapies. All of this will ensure that these agents are used appropriately, safely, and efficiently,” they said in their statement.
Bossi P, Botta L, Bironzo P, et al. Systematic review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy. Ann Oncol. 2016;27(suppl-6):320P. https://doi.org/10.1093/annonc/mdw366.05.