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Clinical Trial
. 2024 Dec 19;8(1):149.
doi: 10.1186/s41687-024-00823-8.

Assessing tolerability with the Functional Assessment of Cancer Therapy item GP5: psychometric evidence from LIBRETTO-531, a phase 3 trial of selpercatinib in medullary thyroid cancer

Antoine Regnault  1 , Laurine Bunod  1 , Angely Loubert  1 , Marcia S Brose  2 , Lisa M Hess  3 , Patricia Maeda  3 , Yan Lin  3 , Rebecca M Speck  3 , Adrienne M Gilligan  3 , Nalin Payakachat  4
Affiliations
Clinical Trial

Assessing tolerability with the Functional Assessment of Cancer Therapy item GP5: psychometric evidence from LIBRETTO-531, a phase 3 trial of selpercatinib in medullary thyroid cancer

Antoine Regnault et al. J Patient Rep Outcomes. .

Abstract

Background: This psychometric analysis generated evidence to support the use of the Functional Assessment of Cancer Therapy item GP5 (GP5) as a measure of tolerability and confirms the appropriateness of categorizing "high side-effect burden" using a rating of 3 or 4 (score ranges 0-4) in patients with advanced/metastatic RET-mutant medullary thyroid cancer (MTC).

Methodology: Blinded, pooled interim data from the safety population (n=290) enrolled in the phase 3 LIBRETTO-531 trial (NCT04211337) were used. Intraclass correlation coefficients (ICC) were calculated for test-retest reliability using data from cycles 1-2 post-baseline. Construct validity was evaluated by examining the correlations of GP5 ratings with (a) symptomatic adverse events (AEs; measured by the PRO-CTCAE), and (b) functioning scores of EORTC QLQ-C30. The ability to detect change over time was examined by Cochrane-Mantel-Haenszel tests for GP5 ratings and PRO-CTCAE. The relationship of "high side-effect burden" categories with QLQ-C30 functioning scores was examined.

Results: ICCs for the GP5 ratings after cycle 1 ranged between 0.80 and 0.85, indicating good reliability. Correlations between GP5 and PRO-CTCAE items ranged from 0.18 to 0.62 and ranged from -0.37 to -0.50 for QLQ-C30 functioning scores, consistent with study assumptions. Post-baseline GP5 ratings showed significant associations with PRO-CTCAE scores (p<0.001). Participants with GP5 ratings of 3 or 4 had worse physical function than those with GP5 ratings of 0 to 2 (p<0.0001).

Conclusions: This analysis generated evidence supportive of the psychometric properties of the GP5 as a fit-for-purpose measure to assess treatment tolerability in patients with advanced/metastatic MTC. The definition of "high side-effect burden" was associated with the clinical feature of tolerability.

Keywords: FACT item GP5; Medullary thyroid cancer; Patient-reported tolerability; Psychometric analysis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was conducted in accordance with consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines. Consent for publication: All authors read and approved the final manuscript. Competing interests: AMG, LMH, NP, PM, RS, and YL are employed by Eli Lilly and Company. AR, AL, and LB are employees of Modus Outcomes, which received payment from Eli Lilly and Company to conduct this research. MSB reports consultancy role for Aadi Bioscience, Bayer, Blueprint, Eisai, Eli Lilly and Company, Exelixis, Ipsen.

Figures

Fig. 1
Fig. 1
Distribution of QLQ-C30 functioning and quality of life/global health scores according to GP5 at cycle 3
Fig. 2
Fig. 2
Distribution of the GP5 at the 4 assessments before treatment discontinuation and first assessment after treatment discontinuation in patients who discontinued treatment due to AE or personal decision, in relation the to the benchmark group
Fig. 3
Fig. 3
QLQ-C30 Physical functioning (Panel A) and Quality of Life/Global health status (Panel B) score according to high side-effect burden. F-statistic and parametric P-value for between-group comparisons: ANOVA for continuous variables
See this image and copyright information in PMC

References

    1. Basch E, Campbell A, Hudgens S, Jones L, King-Kallimanis B, Kluetz P et al (2018) Broadening the definition of tolerability in cancer clinical trials to better measure the patient experience. Friends Cancer Res 10
    1. US Federal Drug Administration (2021) Core patient-reported outcomes in cancer clinical trials: draft guidance for industry
    1. Peipert JD, Smith ML (2022) Reconsidering tolerability of cancer treatments: opportunities to focus on the patient. Support Care Cancer 30(5):3661–3663. 10.1007/s00520-021-06700-0 - PMC - PubMed
    1. Kluetz PG, Chingos DT, Basch EM, Mitchell SA (2016) Patient-reported outcomes in cancer clinical trials: measuring symptomatic adverse events with the National Cancer Institute’s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Am Soc Clin Oncol Educ Book 36:67–73. 10.1200/edbk_159514 - PubMed
    1. Gilbert A, Piccinin C, Velikova G, Groenvold M, Kuliś D, Blazeby JM et al (2022) Linking the European Organisation for Research and Treatment of Cancer Item Library to the common terminology criteria for adverse events. J Clin Oncol 40(32):3770–3780. 10.1200/jco.21.02017 - PMC - PubMed

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