{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T01:49:18Z","timestamp":1787968158921,"version":"build-2784847793"},"reference-count":18,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      -mutant medullary thyroid cancer (MTC).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods:<\/jats:title>\n                    <jats:p>Patients were self-administered the single Functional Assessment of Cancer Therapy item GP5: \u201cI am bothered by side effects\u201d weekly, and scores were dichotomized into \u201clow\u201d (0\u20132) and \u201chigh\u201d (3\u20134) side-effect burden. PRT measured the proportion of time on treatment (PTT) with \u201chigh\u201d 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      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 \u201chigh side-effect burden\u201d than control (8% vs. 24%,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 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\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.01); and significantly less PTT with severe diarrhea (5% vs. 38%), fatigue (6% vs. 21%), taste change (3% vs. 15%), decreased appetite (2% vs. 15%), and hand-foot syndrome (2% vs. 9%) (all\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      This study demonstrated superior PRT for selpercatinib compared with control in patients with\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      -mutant MTC, further supporting selpercatinib use as the first-line treatment for patients with advanced\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      -mutant MTC. Comparative PRT deserves further adoption as a complement to traditional endpoints in future randomized-controlled trials.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10507256251367352","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T18:52:36Z","timestamp":1759949556000},"page":"1162-1172","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Patient-Reported Tolerability of Selpercatinib Compared to Cabozantinib\/Vandetanib: A Secondary Analysis of the LIBRETTO-531 Randomized-Controlled Trial in\n                    <i>RET<\/i>\n                    -Mutant Medullary Thyroid Cancer"],"prefix":"10.1177","volume":"35","author":[{"given":"Rossella","family":"Elisei","sequence":"first","affiliation":[{"name":"Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2629-2289","authenticated-orcid":false,"given":"Lori J.","family":"Wirth","sequence":"additional","affiliation":[{"name":"Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaume","family":"Capdevila","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Vall d\u2019Hebron Institute of Oncology, Universitat Aut\u00f2noma de Barcelona, Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Oliveira","family":"Hoff","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo, Universidade de S\u00e3o Paulo, S\u00e3o Paulo and Instituto D\u2019 OR de Pesquisa e Ensino, S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Tahara","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mimi I.","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Hua","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, Zhejiang Provincial People\u2019s Hospital, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Wadsley","sequence":"additional","affiliation":[{"name":"Weston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Vaisman","sequence":"additional","affiliation":[{"name":"Endocrinologia Oncol\u00f3gica, Instituto Nacional do Cancer, Rio de Janeiro, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Kopeckova","sequence":"additional","affiliation":[{"name":"Department of Oncology, 2nd Faculty of Medicine of Charles University and Motol University Hospital, Prague, Czech Republic."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolanta","family":"Krajewska","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinorath","family":"Olvera","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin","family":"Churchill","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Maeda","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne M.","family":"Gilligan","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Lin","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nalin","family":"Payakachat","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Robinson","sequence":"additional","affiliation":[{"name":"Sydney Medical School, University of Sydney, Sydney, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1276-3289","authenticated-orcid":false,"given":"Julien","family":"Hadoux","sequence":"additional","affiliation":[{"name":"Service d\u2019Oncologie Endocrinienne, D\u00e9partement d\u2019imagerie, Gustave Roussy and ENDOCAN-TUTHYREF Network, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia S.","family":"Brose","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1200\/jco.22.00535"},{"key":"e_1_3_7_3_2","unstructured":"Broadening the definition of tolerability in cancer clinical trials to better measure the patient experience. 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Content Validity of FACT-GP5 to Assess Treatment Tolerability in Participants with Progressive, Advanced, Kinase Inhibitor-Na\u00efve, RET-Mutant Medullary Thyroid Cancer: Qualitative Interview Sub-Study of the LIBRETTO-531 Trial. Atlanta, GA; 2024."},{"key":"e_1_3_7_14_2","volume-title":"Evidence to Support the Use of the Functional Assessment of Cancer Therapy \u2013 General Item (FACT-GP5) to Assess Comparative Tolerability Endpoint:","author":"Regnault A","year":"2024","unstructured":"Regnault A, , Bunod L, , Loubert A, et al. Evidence to Support the Use of the Functional Assessment of Cancer Therapy \u2013 General Item (FACT-GP5) to Assess Comparative Tolerability Endpoint:. 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