Page 55 - Read Online

Webster et al. J Cancer Metastasis Treat 2020;6:8 I http://dx.doi.org/10.20517/2394-4722.2019.38 Page 3 of 14

almost any organ system, and can be potentially life-threatening (e.g., colitis and pneumonitis). They
include the development of inflammatory and autoimmune conditions with unpredictable onset, as well
as delayed and late effects that may persist long after treatment ends and require ongoing treatment with
immunosuppressive agents in some cases [5,16] .

In the oncology community, recent efforts to catalog and classify ICM-associated toxicities and to set
standardized management guidelines are helping treating clinicians understand the complexities of
immunotherapy and to better diagnose and manage their patients’ symptoms. Importantly, between 2017
and 2018, extensive guidelines for the management of immunotherapy-related toxicities were issued by the
National Comprehensive Cancer Network in collaboration with the American Society of Clinical Oncology,
the European Society for Medical Oncology, and the Society for Immunotherapy of Cancer Toxicity
Management Working Group [4,9,10] . Nevertheless, the era of immunotherapy is still in its infancy; more
data are needed to understand risk factors, clinical phenotypes, and the nature, trajectory, and severity of
short- and long-term immunotherapy-related toxicities, as well as the requirements for and responses to
other immunosuppressive agents. These data are needed to more accurately inform clinicians and patients
about how such toxicities affect the therapeutic risk-benefit ratio associated with ICMs. The availability
of a patient-reported, targeted symptom assessment of irAEs for use in both the clinical trial and clinical
practice settings would help address this important need.

Patient-reported outcome assessment in immunotherapy
Patient-reported outcome (PRO) data represent a rich and currently underutilized resource that can
contribute significantly to our knowledge of patients’ experiences with symptoms of cancer, its treatment,
and impact on health-related quality of life (HRQOL). PROs are defined as “any report of the status of a
patient’s (or person’s) health condition, health behavior, or experience with healthcare that comes directly
[17]
from the patient, without interpretation of the patient’s response by a clinician or anyone else” . In clinical
trials, PROs enhance understanding of treatment toxicity, HRQOL, and treatment value [18-22] . In clinical
practice, PROs aid early symptom detection, symptom management, and treatment decision making [23-27] .

PRO measurement systems frequently used in oncology include the Functional Assessment of Chronic
Illness Therapy Measurement System (FACIT), the European Organisation for Research and Treatment
of Cancer (EORTC), and the Patient-Reported Outcomes Measurement Information System (PROMIS)
[28-30] . FACIT, EORTC, and PROMIS systems provide valid and reliable measurement of disease-related
physical, functional, social, and emotional concerns and some treatment toxicities. More recently, Basch
and colleagues developed the Patient-Reported Outcomes-Common Terminology Criteria for Adverse
TM
Events (PRO-CTCAE ) measurement system, a compendium of PRO items uniquely targeted to the
assessment of symptomatic treatment-related toxicities in oncology care . PRO-CTCAE allows for the
[31]
use of individually selected questions drawn from a pool of over 100 items organized into 14 National
Comprehensive Cancer Network (NCCN)-designated toxicity domains, advancing the acceptability of
customizable forms. Although these measurement systems have advanced our understanding of treatment
toxicity and HRQOL, they were developed prior to the widespread use of ICMs. To date, there are no
established PRO measures that assess the full range of common and unique symptoms of AEs related to
ICM treatment [32,33] .

We therefore set out to develop an inclusive list and a library of patient-reported items that assess
adverse events associated with immunotherapy, intended to be conceptually and structurally similar to
the PRO-CTCAE, enabling selective assessment of subsets for specific use. In this paper, we report on
the development of a conceptual framework and extensive FACIT Immunotherapy Item Library. We
also describe the parallel development of a Primary Symptom List, a representative subset of library
items selected by our expert panel via a modified Delphi technique. The FACIT Immunotherapy Item