A new report from the Association of Community Cancer Centers (ACCC) predicts that more and more patients are likely to benefit from immunotherapy treatments, and more of these treatments will be given in community settings. The report, "Immuno-Oncology in 2020: What We've Learned and What Lies Ahead," was produced by the ACCC's Immuno-Oncology Institute, which was launched in 2015 to provide multidisciplinary cancer care teams with resources, guidance on reimbursement, insights from leading experts in the field of immunotherapy (IO), and help in managing survivors.
Immunotherapy has been growing steadily in importance in the field of oncology. In its 2019 Cancer Progress Report, the American Association for Cancer Research (AACR) referred to immunotherapy as "the fifth pillar of cancer care" and "one of the most exciting new approaches to cancer treatment that has entered the clinic. Clearly the new immunotherapeutics and treatment strategies that are on the horizon hold extraordinary promise for the future."
ACCC Immunotherapy Report
The ACCC's new report on immuno-oncology notes that there are several key reasons for the expected expansion of IO in cancer care, including the following:
* While most IO drug approvals have been based on data from clinical trials with patients who have late-stage or metastatic cancer, "checkpoint inhibitors are emerging as feasible therapies in many adjuvant and neoadjuvant settings, such as in triple-negative breast cancer," states the report. The new report notes that PD-1 and CTLA-4 inhibitors are currently approved for the treatment of surgically resected melanoma, while a number of ongoing trials are showing promise for IO in a range of other solid tumors.
* IO therapies are now being used increasingly as an integral part of a combination treatment regimen or in sequence with chemotherapy and targeted drugs. According to the report, "76 percent of currently active PD-1/PD-L1 trials are testing combination regimens of checkpoint inhibitors with other IO agents, targeted therapies, chemotherapies, or radiotherapy."
* An ever increasing number of cancer patients no longer have to travel to academic medical centers to receive IO. As the report states, "IO treatment is increasingly being delivered in community cancer programs and is no longer the predominant purview of academic cancer centers."
"I think the huge learning curve that IO presented has significantly flattened out just by virtue of the explosive availability of IO therapies in the community, and the sheer necessity for physicians to learn to work with this particular class of drug. In many cases it has become the standard of care, and if you want to practice oncology today, you have to understand it," said Sigrun Hallmeyer, MD, Chair of the ACCC Immuno-Oncology Institute's Executive Committee. Hallmeyer is Director of the Cancer Institute and Medical Director of the Cancer Survivorship Program at Advocate Lutheran General Hospital in Park Ridge, IL, and Co-Director of the PRC Russell Institute for Research and Innovation.
The new report notes that nearly 10 years have passed since the FDA approved the first immune checkpoint inhibitor drug for treatment of unresectable or metastatic melanoma. Currently IO therapies have been approved to treat more than 20 types of cancer, as well as cancers with specific genetic mutations. Nine checkpoint inhibitors have been approved by the FDA for 16 tumor types and tissue-agnostic indications. In addition, two CAR T-cell therapies have been approved for certain types of non-Hodgkin lymphoma and acute lymphoblastic lymphoma. Additionally, there are at least 567 active clinical trials in phase II investigating cell therapies, cancer vaccines, and oncolytic virus immunotherapy. "Current available therapies represent the tip of the iceberg," states the new report.
On the horizon are CD3-targeted antibody therapies for patients who progress following CAR T-cell therapy, as well as strategies to manage CAR-T-associated toxicities, according to the new report. These include modified natural killer cells for patients with relapsed or refractory CD19-positive lymphoid tumors.
The report notes that a predicted "expanded array of therapies will intensify the need to find answers to clinical questions and develop resources concerning the validity and interpretation of biomarkers to inform patient selection, toxicity prediction, and when to discontinue IO in patients with stable disease."
While the expansion of IO in the community is good news for cancer patients, because of complexities and toxicities inherent in the field, this expansion comes at a cost to community oncology programs, according to the report. As it states, "the implementation of IO treatment in community cancer programs may hold higher demands in terms of resources, expertise, and time. Notably, the pharmacodynamic profile of IO therapies results in distinct incidence and types of toxicity such that immune-related adverse events (irAEs) can be unpredictable and delayed in presentation." A new challenge, and a welcome result of the success of IO treatment, is the need to plan for survivorship care in patients receiving these therapies.
Focus Areas in Immuno-Oncology
To help community oncologists and cancer care teams navigate an increasingly complicated and expanding IO clinical landscape, the ACCC IO Institute has set four major foundational areas of emphasis.
1. Cancer care team training and education. The report notes that multidisciplinary cancer care teams now consist of a broad range of providers, including oncologists, non-oncology specialists, advanced practice providers, financial navigators, pathologists, and survivorship care planning teams. The report predicts that CAR T-cell therapy clinical trials may expand to outpatient settings for patients with diffuse large B-cell lymphoma. Outpatient delivery could extend the availability of CAR T-cell therapy to patients who lack access to major academic hospitals or treatment centers.
'The report states, "The ACCC IO Institute will continue to support strategies that bring IO to community settings, educate the cancer care team on irAE management, and build capacity in multidisciplinary care coordination to support community-based immunotherapy."
Hallmeyer noted that "IO and survivorship have become practically synonymous, as IO is delivering on the promise of helping cancer patients live longer. This means our focus must include delivering resources to the whole care team delivering survivorship care. It's a welcome set of new challenges."
2. Multispecialty communication and coordination. The ACCC report states that as more and more cancer patients are treated with immunotherapy, the cancer care team will need to coordinate effectively with non-oncology specialists. The ACCC IO Institute plans to continue investing in educational and training initiatives that support multidisciplinary care delivery, such as integrating non-oncology providers into the toxicity team and expanding the capacity to develop quick, coordinated responses to emerging irAEs through the use of virtual toxicity teams. Other issues that fall under this foundational area include when to discontinue IO treatment in stable patients, how to handle financial toxicity for patients due to the high costs of care and loss of income during treatment, how to use patient-centric metrics in evaluating IO, and developing resources to support long-term survivorship care planning.
3. Applying big data and research into practice. Today, bioinformatics, large-scale quantitative data mining and "deep analytics" are increasingly being used to gather and map immune system and patient response data, notes the report. So-called "big data" are being used to accelerate the development of breakthrough IO therapies, identify novel cancer biomarkers, predict toxicity, and solidify the evidence base for cancer immunotherapy.
The ACCC IO Institute plans to coordinate and collaborate with thought leaders on predictive biomarkers for patient selection and irAE prediction, use of liquid biopsy for predicting and evaluating the response to immunotherapy through circulating tumor DNA, and issues related to securing biomarker testing reimbursement and integrating validated biomarkers into practice, including the use of next-generation sequencing technology for microsatellite instability/mismatch repair deficiency and tumor mutational burden.
4. Telemedicine, technology, and virtual patient navigation. The new ACCC report notes that "the demand for cancer care services in a growing population underscores the importance of telemedicine and technology as a vital component of delivering high-quality, value-based cancer care." Therefore, the ACCC IO Institute plans to continue to explore the potential of telemedicine in remote patient monitoring. Specifically, the institute plans to investigate ways of acquiring platforms that integrate with electronic health records and meet clinical requirements, as well as navigating telemedicine reimbursement policies.
"We will continue to focus on the management of irAEs and survivorship care for patients treated with immunotherapy," said Hallmeyer. "At the same time, we will be looking to the future with initiatives related to big data and quality improvement. We will continue to refine and advance our reputation of being the 'how to' resource for clinicians practicing in the ever-expanding field of IO."
Peggy Eastman is a contributing writer.