From a Patient Advocate's Perspective: Does Cancer Immunotherapy Represent a Paradigm Shift?

Abstract

Purpose of review: In 2016, the American Society of Clinical Oncology (ASCO) announced immunotherapy as the year's top cancer advance in its "Clinical Cancer Advances 2016: ASCO's Annual Report on Progress Against Cancer." Further, ASCO again named "Immunotherapy 2.0" as the 2017 advance of the year, emphasizing the recent, rapid pace of research into new agents that harness and enhance the innate abilities of the immune system to recognize and fight cancers-and stressing that such agents have extended the lives of many patients with late-stage cancers for which there have been few treatment options. This article discusses the history of cancer immunotherapy and the recent promising advances, yet also presents a note of caution on limitations of immunotherapies, their potential harms, and the critical need for oncologists to appropriately engage with and educate patients to effectively manage their expectations.

Recent findings: Learning how to effectively harness the immune system to treat cancer represents an investigative journey of more than 100 years. However, after many failures and disappointments, this decade has seen several important successes. In 2011, the Food and Drug Administration (FDA) approved the first immunotherapy agent known as a "checkpoint inhibitor." Beginning in 2014, several additional checkpoint blockage drugs have been FDA-approved, and new indications and drug combinations have emerged. Further, on August 30, 2017, the FDA announced its first approval of a new form of immunotherapy known as CAR T cell therapy. Since the 2011 approval of the first checkpoint inhibitor, cancer immunotherapy research among the pharmaceutical industry and research institutions has exploded, with thousands of clinical trials currently taking place. The current "cancer immunotherapy revolution" is in the headlines daily and is also the primary topic of conversation among major cancer research conferences and symposia attendees. However, a once quiet voice has begun to emerge, where an increasing number of scientists, clinicians, and patient advocates are stressing the need for caution concerning the limitations and potential harms associated with cancer immunotherapy. Many oncologists, scientists, medical professional associations, and advocates agree that no recent cancer advance has been as successful, transformative, and potentially paradigm-shifting as immunotherapy. With this decade, we have seen the approval of several immunotherapy agents that have successfully treated a percentage of patients with notoriously resistant cancers, an increasing number of combination immunotherapy treatments, and new indications for approved agents. However, patients need to be aware that much of the popular media has breathlessly inflated positive outcomes of cancer immunotherapies, while neglecting to stress that just a small percentage of patients actually benefit from such treatments. Further, they often completely overlook the unique, potentially life-threatening harms that may be associated with these agents and fail to cover negative findings where immunotherapies have appeared to paradoxically accelerate cancer growth. Fortunately, the majority of journal articles presenting trial results and comprehensive review articles appropriately discuss the important limitations associated with immunotherapies, the unique spectrum of adverse effects, and the need for further research to improve our ability to identify those patients who are most likely to benefit from specific agents, sparing other patients from exposure to agents that will not be effective, yet may carry potentially life-threatening toxicities.

Keywords: Adoptive cell transfer (ACT); CAR T cell therapy; CTLA-4 checkpoint inhibitors; Cancer immunotherapy; Cancer research advocacy; Cancer vaccines; Checkpoint inhibitors; Clinical oncology; Cytokine release syndrome (CRS); Immune-related adverse events (irAEs); Immunotherapy in the media; Immunotherapy: hope or hype?; Late-stage cancers; Monoclonal antibodies; PD-1 checkpoint inhibitors; Patient education; Refractive cancers; Solid tumors; T cells; Targeted therapies; “Pseudo-progression”.