| Title: |
Patient-reported tolerability of selpercatinib compared to Cabozantinib/Vandetanib: a secondary analysis of the LIBRETTO-531 randomized-controlled trial in RET-mutant medullary thyroid cancer |
| Authors: |
Elisei, R.; Wirth, L.J.; Capdevila, J.; Hoff, A.O.; Tahara, M.; Sherman, E.J.; Hu, M.I.; Ge, M.-H.; Wadsley, J.; Vaisman, F.; Kopeckova, K.; Krajewska, J.; Olvera, D.; Churchill, C.; Maeda, P.; Gilligan, A.M.; Lin, Y.; Payakachat, N.; Robinson, B.; Hadoux, J.; Brose, M.S. |
| Publisher Information: |
SAGE Publications |
| Publication Year: |
2025 |
| Collection: |
White Rose Research Online (Universities of Leeds, Sheffield & York) |
| Description: |
Background: Progression-free survival (PFS) may not fully capture the impact of treatment on patients, especially in cancers with longer natural histories and thus, could be complemented by robust measures of patient-reported tolerability (PRT). We report the use of a novel, quantifiable PRT metric as a multiplicity-controlled endpoint to support regulatory and clinical decision-making for selpercatinib use. Comparative PRT was assessed in LIBRETTO-531 (NCT04211337), a randomized phase 3 trial of selpercatinib versus vandetanib/cabozantinib (control) in advanced RET-mutant medullary thyroid cancer (MTC). Patients and Methods: Patients were self-administered the single Functional Assessment of Cancer Therapy item GP5: “I am bothered by side effects” weekly, and scores were dichotomized into “low” (0-2) and “high” (3-4) side-effect burden. PRT measured the proportion of time on treatment (PTT) with “high” side-effect burden for each patient. Comparative PRT was tested at a two-sided significance level of 0.05, conditional on achieving significance for efficacy endpoints. Complementary patient-reported outcomes included health-related quality of life (HRQoL) and symptomatic adverse events self-administered at baseline and at different intervals post-baseline during treatment period. Results: In the tolerability evaluable population (N = 242; selpercatinib n = 161 and control n = 81 [56 received cabozantinib, 25 received vandetanib]), patients on selpercatinib had significantly better PRT with lower PTT with “high side-effect burden” than control (8% vs. 24%, p < 0.0001). Post-baseline compliance rates for PRO questionnaires were generally greater than 80% in both treatment groups. Patients on selpercatinib reported significantly less PTT with HRQoL impairment across physical (36% vs. 52%), role (2% vs. 11%), cognitive (4% vs. 8%), emotional (6% vs. 11%), and social (2% vs. 8%) function (all p < 0.01); and significantly less PTT with severe diarrhea (5% vs. 38%), fatigue (6% vs. 21%), taste change (3% vs. ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| ISSN: |
1050-7256 |
| Relation: |
https://eprints.whiterose.ac.uk/id/eprint/233055/1/elisei-et-al-2025-patient-reported-tolerability-of-selpercatinib-compared-to-cabozantinib-vandetanib-a-secondary.pdf; Elisei, R., Wirth, L.J. orcid.org/0000-0002-2629-2289 , Capdevila, J. et al. (18 more authors) (2025) Patient-reported tolerability of selpercatinib compared to Cabozantinib/Vandetanib: a secondary analysis of the LIBRETTO-531 randomized-controlled trial in RET-mutant medullary thyroid cancer. Thyroid, 35 (10). pp. 1162-1172. ISSN: 1050-7256 |
| DOI: |
10.1177/10507256251367352 |
| Availability: |
https://eprints.whiterose.ac.uk/id/eprint/233055/; https://doi.org/10.1177/10507256251367352 |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.FAFE35B6 |
| Database: |
BASE |