Page 54 - Read Online

Page 2 of 14 Webster et al. J Cancer Metastasis Treat 2020;6:8 I http://dx.doi.org/10.20517/2394-4722.2019.38

Methods: Literature review and iterative expert input. Based on a literature review of irAEs, we developed a
framework of immunotherapy classes and their associated symptoms. Clinical experts then reviewed iterations
of symptom summaries and item maps linked to the immunotherapy framework. Experts provided content review
and feedback was shared across experts until consensus was reached. The iterative process facilitated creation
of a Primary Symptom List associated with immune checkpoint modulators (ICMs), drawn from the larger set of
symptoms. Existing FACIT items were mapped to the symptom list, and new items were written as needed to create
the item library.

Results: The full item library of irAEs is comprised of 239 items, covering 142 unique symptoms across 75 inflammatory
reactions/immune conditions. A subset of 66 items comprises a Primary Symptom List considered most common/
relevant to ICM treatment. This includes gastrointestinal, skin, pulmonary, neurologic, musculoskeletal, and multiple
miscellaneous and constitutional symptoms.

Conclusion: The FACIT Immunotherapy Item Library is a compilation of 239 self-report items that capture the wide
range of AEs experienced by people receiving immune treatments. A subset of 66 items comprises a Primary
Symptom List meant for ICM therapy. Use of items selected from this library is encouraged in clinical research and
clinical practice evaluation.

Keywords: Immunotherapy, immune checkpoint modulators, quality of life, immune-related adverse events, patient
reported outcomes, cancer, oncology

INTRODUCTION
The emergence of immune checkpoint modulators (ICMs) in cancer treatment has produced both
optimism and uncertainty among oncologists and patients. Over the last decade, the demonstrated
efficacy of cytotoxic lymphocyte antigen-4 (CTLA-4) inhibitors, programmed cell death protein-1 (PD-1)
inhibitors, and PD-1 ligand (PD-L1) inhibitors to induce prolonged responses in advanced cancers has
[1-3]
been well-documented . Such results were first noted in the treatment of metastatic melanoma, and the
United States Food and Drug Administration (FDA) has since approved the use of ICMs for the treatment
of non-small cell lung cancer, renal cell carcinoma, Hodgkin lymphoma, urothelial carcinoma, head and
[4,5]
neck cancers, and other tumors . A recent meta-analysis of randomized clinical trial data involving
the use of anti-PD1/PD-L1 monoclonal antibodies to treat more than 6500 patients confirmed increased
[6]
overall response rates when compared to usual care, including chemotherapy and targeted therapy . While
the greatest gains were seen in patients with melanoma and those treated in the first-line setting, improved
response rates associated with ICMs were seen across all tumor types. However, despite justifiable
optimism surrounding ICMs and other biologic therapies, their relative success is tempered by uncertainty
as to which patients are likely to benefit, and new challenges in the detection and management of a host
[7]
of potential short- and long-term adverse events unique to immune-mediated therapy . Clinicians and
patients discussing treatment options for advanced cancer must balance this ambiguity alongside their
[8]
desire to pursue every possible path toward longer life .

ICM treatment tolerability can complicate treatment decision-making, even for those patients who are
promising candidates for ICM therapy. Immune-related adverse events (irAEs), including gastrointestinal,
dermatologic, endocrinologic, cardiopulmonary, musculoskeletal, and other autoimmune complications,
occur in many patients treated with ICMs [4,9-15] . One study found that adverse events occur in up to 90%
[13]
of patients treated with CTLA-4 and 70% of patients treated with anti-PD-1/PD-L1 agents . In trials
using single anti-PD-1/PD-L1 agents, the rates of Grade 3 and 4 toxicities capable of hospitalizing patients
and leading to treatment discontinuation ranged from 10% to 20% . IrAEs are diverse, can impact
[7]