Questionnaire-based detection of immune-related adverse events in cancer patients treated with PD-1/PD-L1 immune checkpoint inhibitors

Luisa Maria Griewing, Claudia Schweizer, Philipp Schubert, Sandra Rutzner, Markus Eckstein, Benjamin Frey, Marlen Haderlein, Thomas Weissmann, Sabine Semrau, Antoniu-Oreste Gostian, Sarina K Müller, Maximilian Traxdorf, Heinrich Iro, Jian-Guo Zhou, Udo S Gaipl, Rainer Fietkau, Markus Hecht, Luisa Maria Griewing, Claudia Schweizer, Philipp Schubert, Sandra Rutzner, Markus Eckstein, Benjamin Frey, Marlen Haderlein, Thomas Weissmann, Sabine Semrau, Antoniu-Oreste Gostian, Sarina K Müller, Maximilian Traxdorf, Heinrich Iro, Jian-Guo Zhou, Udo S Gaipl, Rainer Fietkau, Markus Hecht

Abstract

Background: Immune checkpoint inhibitors (ICI) have become standard treatment in different tumor entities. However, safe treatment with ICI targeting the PD-1/PD-L1 axis requires early detection of immune-related adverse events (irAE). There exist different questionnaires of drug manufacturers for the detection of irAE that have not been validated so far.

Methods: The prospective non-interventional ST-ICI trial studied treatment with PD-1/PD-L1 ICI alone or combined with radiotherapy. In the current analysis, the detection rate of self-reported irAE with a patient questionnaire containing 41 different questions was compared to clinician-reported irAE.

Results: Between April 2017 and August 2019, a total of 104 patients were prospectively enrolled. NSCLC (44%) and HNSCC (42%) were the most frequent tumor entities. A total of 784 questionnaires were collected. A total of 29 irAE were reported by clinicians. The most frequent irAE was hypothyroidism (9%), followed by skin reactions (5%), hepatitis (4%), diarrhea (3%), and pneumonitis (3%). Questions that became significantly more often positive at time points of clinician-reported irAE were "weight change", "difficulty to grip things", "bloody or mucous stool" and "insomnia". Self-reported organ-specific questions detected at least 50% of clinician-reported irAE of gastrointestinal, lung, endocrine, and skin irAE. It was not possible to detect hepatic irAE with the questionnaire.

Conclusion: Questionnaires can help to detect gastrointestinal, lung, endocrine, or skin irAE, but not hepatic irAE. Questions on "weight change" and "insomnia" may help to increase the detection rate of irAE, besides organ-specific questions. These results are a valuable contribution to the future development of a specific and practicable questionnaire for early self-reported detection of irAE during ICI therapy in cancer patients.

Trial registration: ClinicalTrials.gov, NCT03453892 . Registered on 05 March 2018.

Keywords: Immune checkpoint inhibitors; Immune-related adverse events; PD-1; PD-L1; Patient-reported irAE; Questionnaire; Side effects; Solid tumors; Toxicity.

Conflict of interest statement

S.R. conflict of interest with AstraZeneca (research funding); MSD (research funding). M.E. conflict of interest with Diaceutics (employment, honoraria, advisory role, speakers’ bureau, travel expenses); AstraZeneca (honoraria, advisory role, speakers’ bureau, travel expenses); Roche (honoraria, travel expenses); MSD (honoraria, speakers’ bureau); GenomicHealth (honoraria, advisory role, speakers bureau, travel expenses); Astellas (honoraria, speakers’ bureau); Janssen-Cilag (honoraria, advisory role, research funding, travel expenses); Stratifyer (research funding, patents). S.S. conflict of interest with Strycker (stock); Varian (stock); Abbot (stock); Crispr Techn. (stock); Pfitzer (stock); Merck Serono (stock); Symrise (stock); Ortho (honoraria, advisory role, speakers’ bureau, research funding, travel expenses); PharmaMar (speakers’ bureau, travel expenses); Haema (speakers’ bureau). U.S.G. conflict of interest with AstraZeneca (advisory role, research funding); BMS (advisory role); MSD (research funding); Sennewald Medizintechnik (travel expenses). R.F. conflict of interest with MSD (honoraria, advisory role, research funding, travel expenses); Fresenius (honoraria); BrainLab (honoraria); AstraZeneca (honoraria, advisory role, research funding, travel expenses); Merck Serono (advisory role, research funding, travel expenses); Novocure (advisory role, speakers’ bureau, research funding); Sennewald (speakers’ bureau, travel expenses). The other authors declare no conflicts of interest. M.He. conflict of interest with Merck Serono (advisory role, speakers’ bureau, honoraria, travel expenses, research funding); MSD (advisory role, speakers’ bureau, travel expenses, research funding); AstraZeneca (research funding); Novartis (research funding); BMS (advisory role, honoraria, speakers’ bureau); Teva (travel expenses). The other authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
ST-ICI trial: irAE assessment. Assessment of irAE with easily routinely usable binary response questions (yes/no) focusing on the most affected organ systems
Fig. 2
Fig. 2
Frequency of positive answers of the ST-ICI cohort depending on clinician-reported irAE. a Gastrointestinal irAE. b Pulmonary irAE. c Endocrine irAE. d Skin irAE. e Hepatic irAE. f Neurologic irAE. g Renal irAE. h Non-specific irAE

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Source: PubMed

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