From the Journals

New toxicity subscale measures QOL in cancer patients on checkpoint inhibitors


 

FROM CANCER

A new tool specifically designed to evaluate immune checkpoint inhibitor–related toxicity, developed based on direct patient involvement, picks up on cutaneous and other side effects that would be missed using traditional quality of life questionnaires, investigators say.

The 25-item list represents the first-ever health-related quality of life (HRQOL) toxicity subscale developed for patients receiving checkpoint inhibitors, according to the investigators, led by Aaron R. Hansen, MBBS, of the division of medical oncology and hematology in the department of medicine at the University of Toronto.

The toxicity subscale is combined with the Functional Assessment of Cancer Therapy–General (FACT-G), which measures physical, emotional, family and social, and functional domains, to form the Functional Assessment of Cancer Therapy–Immune Checkpoint Modulator (FACT-ICM), Dr. Hansen stated in a recent report that describes initial development and early validation efforts.

The FACT-ICM could become an important tool for measuring HRQOL in patients receiving checkpoint inhibitors, depending on results of further investigations including more patients, the authors wrote in that report.

“Currently, we would recommend that our toxicity subscale be validated first before use in clinical care, or in trials with QOL as a primary or secondary endpoint,” wrote Dr. Hansen and colleagues in the report, which appears in Cancer.

The toxicity subscale asks patients to rate items such as “I am bothered by dry skin,” “I feel pain, soreness or aches in some of my muscles,” and “My fatigue keeps me from doing the things I want do” on a scale of 0 (not at all) to 4 (very much).

Development of the toxicity subscale was based on focus groups and interviews with 37 patients with a variety of cancer types who were being treated with a PD-1, PD-L1, and CTLA-4 immune checkpoint inhibitors. Sixteen physicians were surveyed to evaluate the patient input, while 11 of them also participated in follow-up interviews.

“At every step in this process, the patients were central,” the investigators wrote in their report.

According to the investigators, that approach is in line with guidance from the Food and Drug Administration, which has said that meaningful patient input should be used in the upfront development of patient-reported outcome (PRO) measures, rather than obtaining patient endorsement after the fact.

By contrast, an electronic PRO immune-oncology module recently developed, based on 19 immune-related adverse events from drug labels and clinical trial reports, had “no evaluation” of effects on HRQOL, according to Dr. Hansen and coauthors, who added that the tool “did not adhere” to the FDA call for meaningful patient input.

Some previous studies of quality of life in immune checkpoint inhibitor–treated patients have used tumor-specific PROs and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 Items (EORTC-QLQ-C30).

The new, immune checkpoint inhibitor–specific toxicity subscale has “broader coverage” of side effects that reportedly affect HRQOL in patients treated with these agents, including taste disturbance, cough, and fever or chills, according to the investigators.

Moreover, the EORTC-QLQ-C30 and the EORTC head and neck cancer–specific-35 module (EORTC QLQ-H&N35), do not include items related to cutaneous adverse events such as itch, rash, and dry skin that have been seen in some checkpoint inhibitor clinical trials, they noted.

“This represents a clear limitation of such preexisting PRO instruments, which should be addressed with our immune checkpoint moduator–specific tool,” they wrote.

The study was supported by a grant from the University of Toronto. Authors of the study provided disclosures related to Merck, Bristol-Myers Squibb, Karyopharm, Boston Biomedical, Novartis, Genentech, Hoffmann La Roche, GlaxoSmithKline, and others.

SOURCE: Hansen AR et al. Cancer. 2020 Jan 8. doi: 10.1002/cncr.32692.

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