In 1986, interferon-α was the first modern immunotherapy agent to receive approval for the treatment of hairycell leukemia. A little more than 20 years later, the 2018 Nobel Prize in Physiology was awarded to James P. Allison and Tasuku Honjo for their work leading to the discovery of a way to block immune checkpoint pathways that are essential for cancer cell growth and proliferation. Since then, immunotherapy has continued to garner interest as a powerful treatment option for many types of cancer, and as of 2020, 15-20% of patients achieve durable results with immunotherapy, and more than 70 immunotherapy drugs are in the clinical pipeline. In addition, immuno-oncology (I-O) has its own stock index of 25 companies worth $100 million or more.
What exactly is I-O? UC San Diego Health defines it as treatment that uses the immune system to fight cancer by harnessing immune cells’ natural ability to detect and eliminate substances or cells that may be harmful to the body.
Currently, there are many different immunotherapies available to patients for the treatment of more than 20 cancer types. These are divided into five classes depending on the mechanism involved in eliciting an immune response to target cancer cells: cell-based immunotherapies, treatments that use immunomodulators, vaccines, antibody-based targeted therapies and treatments that employ oncolytic viruses.
One of the advantages of immunotherapy is that it has the potential to reach diseased areas that more conventional treatments like surgery cannot. Immunotherapy can also be used to target microscopic tumors and metastases that are not visible in imaging studies, and to attack cancer cells that are not rapidly dividing, but still capable of spreading disease. Immunotherapy can also train the immune system's "memory cells" for long-term anti-cancer protection.
Malignant and non-malignant components of tumors, as well as the mediators of their intercellular communication, are all potential targets for immunotherapy. The two main drivers behind the initial success of I-O are checkpoint inhibitors (CPIs) and chimeric antigen receptor (CAR) T cells.
Resistance and other roadblocks
As with any new health care treatment or drug, there are challenges to understanding I-O research and treating cancer using immuno-oncology therapies. These include complex interactions between a patient’s immune system and the tumor’s biology. Another is resistance to I-O therapies, which can be influenced by tumor types. Below are other important roadblocks to current I-O therapies:
- There are significant challenges for how best to demonstrate the long-term benefit of immunotherapy treatments to health technology assessment agencies, clinicians and payers.
- Tumors can manipulate the immune system in multiple ways to evade detection.
- Therapies that have reached the clinic level only work for some patients.
- As the number of patients exposed to immunotherapies increases, so does the number of patients who can become resistant.
- Patients treated with immunotherapy have shown varying response rates among cancers and within cohorts with the same malignancy.
According to Pharmacy and Therapeutics, a peer-reviewed journal of hospital formulary management, there is a need for additional biomarkers and a lack of clinical study designs that are optimized to determine efficacy. There are also high treatment costs for I-O therapy.
The COVID-19 effect on clinical trials
As with many other fields within the medical industry, the COVID-19 pandemic has negatively impacted I-O research. As of February of this year, 45.1% of ongoing clinical oncology studies were delayed, 33.5% were forced to change protocols and nearly 90% of cancer hospitals suspended new trials completely or partially. In the United States, only 20% of institutions actively researching I-O treatments continued to enroll patients at the usual rate during the pandemic.
Some hospitals and sponsors reported technology-based adaptation measures to overcome operational challenges and ensure participants’ safety, including 65% of the study sites putting ethics committee reviews online. Technology utilized for trial implementation consisted of remote visits, teleconference, drug delivery to patients, centralized monitoring and electronic patient-reported outcomes.
I-O treatments and therapies
Current trends in immuno-oncology focus on the expansion of new I-O pipeline drugs, a sector in which the U.S. leads. The number of active I-O drugs in development grew from 2,030 in 2017 to 3,876 in 2019.
Basket clinical trials, which evaluate one drug in a multitude of tumor types at the same time, enable researchers to review and analyze multiple mechanisms in a single study. A few months ago, a published study led by the University of Southampton in England, and funded by Cancer Research UK, reported that a new drug, Setanaxib, could help to significantly improve the success rate of I-O treatment.
A Journal of Hematology & Oncology article reported that 11 immune checkpoint inhibitors and two chimeric antigen receptor T-cell products have been approved in treating 16 types of malignant diseases and one tissue-agnostic indication.
A similar article, by Pharmacy and Therapeutics, predicted future I-O innovations, such as more targeted treatments, the development of personalized biomarker profiles and drug combination therapies that improve efficacy and reduce toxicity, as well as immune-preventive strategies that will diminish cancer incidence, recurrence and associated treatment costs.
More than half of the studies examining I-O treatment focus on melanoma, followed by brain cancers such as glioblastoma. Another central emphasis is checkpoint inhibitors that target PD-1, a protein that prevents T cells from attacking other cells in the body, and which works paired with PD-L1, a protein abundant in some cancer cells.
Though there are certainly some challenges in I-O research and treatment implementation, many more studies and clinical trials will most likely be completed to expand its efficacy. Subscribe to our blog to keep up-to-date on I-O and other issues affecting the health care industry.
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