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. 2024 Jan 20;42(3):266-272.
doi: 10.1200/JCO.23.00377. Epub 2023 Oct 6.

Importance of Low- and Moderate-Grade Adverse Events in Patients' Treatment Experience and Treatment Discontinuation: An Analysis of the E1912 Trial

Nathaniel S O'Connell  1 , Fengmin Zhao  2 , Ju-Whei Lee  2 , Edward H Ip  1 , John Devin Peipert  3 , Noah Graham  2 , Mary Lou Smith  4 , Ilana F Gareen  5 , Ruth C Carlos  6 , Samilia Obeng-Gyasi  7 , Joseph A Sparano  8 , Tait D Shanafelt  9 , Mary L Thomas  10 , David Cella  3 , Lynne I Wagner  1 , Robert Gray  2
Affiliations

Importance of Low- and Moderate-Grade Adverse Events in Patients' Treatment Experience and Treatment Discontinuation: An Analysis of the E1912 Trial

Nathaniel S O'Connell et al. J Clin Oncol. .

Abstract

Purpose: Despite defined grades of 1 to 5 for adverse events (AEs) on the basis of Common Terminology Criteria for Adverse Events criteria, mild (G1) and moderate (G2) AEs are often not reported in phase III trials. This under-reporting may inhibit our ability to understand patient toxicity burden. We analyze the relationship between the grades of AEs experienced with patient side-effect bother and treatment discontinuation.

Methods: We analyzed a phase III Eastern Cooperative Oncology Group-American College of Radiology Imaging Network trial with comprehensive AE data. The Likert response Functional Assessment of Cancer Therapy-GP5 item, "I am bothered by side effects of treatment" was used to define side-effect bother. Bayesian mixed models were used to assess the impact of G1 and G2 AE counts on patient side-effect bother and treatment discontinuation. AEs were further analyzed on the basis of symptomatology (symptomatic or asymptomatic). The results are given as odds ratios (ORs) and 95% credible interval (CrI).

Results: Each additional G1 and G2 AEs experienced during a treatment cycle increased the odds of increased self-reported patient side-effect bother by 13% (95% CrI, 1.06 to 1.21) and 35% (95% CrI, 1.19 to 1.54), respectively. Furthermore, only AEs defined as symptomatic were associated with increased side-effect bother, with asymptomatic AEs showing no association regardless of grade. Count of G2 AEs increased the odds of treatment discontinuation by 59% (95% CrI, 1.32 to 1.95), with symptomatic G2 AEs showing a stronger association (OR, 1.75; 95% CrI, 1.28 to 2.39) relative to asymptomatic G2 AEs (OR, 1.45; 95% CrI, 1.12 to 1.89).

Conclusion: Low- and moderate-grade AEs are related to increased odds of increased patient side-effect bother and treatment discontinuation, with symptomatic AEs demonstrating greater magnitude of association than asymptomatic. Our findings suggest that limiting AE capture to grade 3+ misses important contributors to treatment side-effect bother and discontinuation.

Trial registration: ClinicalTrials.gov NCT02048813.

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

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