Immunotherapy has burst into oncology drug development during recent years by demonstrating some amazing responses in indications earlier associated with a poor prognosis. The immune checkpoint inhibitors act by restoring and stimulating the patient’s own immune system to fight the tumor. The excitement for immuno-oncology has been noted both in the public news and at scientific conferences, including the 2016 ASCPT and ACoP meetings. Recently, PSP has published six original articles, one perspective, and one commentary on two immune checkpoint inhibitors, pembrolizumab and nivolumab, both approved for clinical use. These significant contributions make up the January issue of PSP and will drive the upcoming launch of a new virtual issue on “Immuno-oncology” found within the Oncology virtual issue.
The recently published immuno-oncology papers demonstrate not only the value of modeling and simulation for understanding pharmacokinetics and pharmacodynamics of the two drugs, but also highlight how modeling and simulation have been valuable for dose selection throughout drug development, i.e. all the way from scaling from preclinical experiments to approval. The performed modeling activities have been important for internal discussions and decisions on their ways toward accelerated approvals, and the developed models and strategies have promise to be valuable in future immuno-oncology projects.
There are a number of challenges for continued and improved drug development in the immuno-oncology area, for example, 1) to identify which patients do benefit from the rather costly treatment, 2) how to best combine immunotherapies with different mechanisms of action, or with other types of anticancer drugs, 3) how to manage toxicities associated with these types of drugs, and 4) to select which indication and trials to perform. To this end pharmacometrics and systems pharmacology, including optimal design methodology, are well suited tools. Pharmacometrics has the power to characterize the time-course of biomarkers, tumor sizes and adverse effects, despite the presence of dropout and the high variability observed in the clinical trials, and for evaluation how responses in these variables are related to prolonged survival. Relationships may hold across indications and for drugs with similar mechanisms of action. Systems pharmacology can be especially valuable to identify combination therapies with a high likelihood of success for a certain indication, both with regards to efficacy and safety. With more efficient clinical trials, founded on model-based designs, it should be possible to more rapidly reach conclusions and selections on a treatment.
It is our expectation that the number of publications on immunotherapy in PSP will increase in the near future and our upcoming virtual issue on Immuno-oncology will have a steady growth. PSP is very much welcoming contributions on modeling concepts, designs and applications in this exciting area. Submit your work today.