Luis E Raez, Ashish C Massey, Scott S Barker, Patrick M Peterson, Katherine Liming, Nathan A Pennell
{"title":"在LIBRETTO-001项目中,色瑞替尼治疗转染过程中RET激活的晚期实体瘤的长期安全性:随着时间推移不良事件的不同模式。","authors":"Luis E Raez, Ashish C Massey, Scott S Barker, Patrick M Peterson, Katherine Liming, Nathan A Pennell","doi":"10.1093/oncolo/oyae282","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Selpercatinib is a selective RET inhibitor approved for treatment of RET-activated cancers. Adverse events (AEs) are manageable with dose modifications. This post hoc analysis characterized selpercatinib's clinical safety profile after long-term follow-up in the safety population of LIBRETTO-001.</p><p><strong>Patients and methods: </strong>LIBRETTO-001 is an ongoing phase I/II, single-arm, open-label trial (NCT03157128). Eligible patients were ≥18 years old with diagnosis of advanced/metastatic RET fusion-positive solid tumor, RET-mutant medullary thyroid cancer, or other RET-activated tumors. In phase I, patients received selpercatinib 20 mg QD or 20-240 mg BID; patients in phase II received 160 mg BID. The analyzed population comprised all patients who received ≥1 selpercatinib dose and were followed up until data cutoff (January 13, 2023).</p><p><strong>Results: </strong>For the 837 patients, median follow-up was 45.4 months (95% CI, 44.5-46.6); median time on treatment was 30.1 months (range 0.1-66.8). Grade ≥3 treatment-emergent AEs (TEAEs) were reported in 76.2% of patients; most common events were hypertension (19.7%), ALT increased (11.8%), and hyponatremia (9.2%). Serious TEAEs were reported in 51.4% of patients. Most frequently reported any-grade AEs at <6 months of treatment were fatigue (36.6%), dry mouth (32.8%), and ALT increased (30.5%); at ≥24 months of treatment, these were edema (63.2%), diarrhea (60.7%), and fatigue (53.0%). Selpercatinib-related TEAEs leading to reduced dosage were reported in 39.3%, those leading to treatment interruption were reported in 47.1%, and those leading to discontinuation were reported in 4.3% of patients.</p><p><strong>Conclusion: </strong>Long-term treatment with selpercatinib is feasible. AEs are manageable with dose modifications, allowing most patients to continue safely on therapy.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":"1068-1078"},"PeriodicalIF":4.8000,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630769/pdf/","citationCount":"0","resultStr":"{\"title\":\"Long-term safety of selpercatinib for Rearranged during transfection (RET)-activated advanced solid tumors in LIBRETTO-001: differing patterns of adverse events over time.\",\"authors\":\"Luis E Raez, Ashish C Massey, Scott S Barker, Patrick M Peterson, Katherine Liming, Nathan A Pennell\",\"doi\":\"10.1093/oncolo/oyae282\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Selpercatinib is a selective RET inhibitor approved for treatment of RET-activated cancers. Adverse events (AEs) are manageable with dose modifications. This post hoc analysis characterized selpercatinib's clinical safety profile after long-term follow-up in the safety population of LIBRETTO-001.</p><p><strong>Patients and methods: </strong>LIBRETTO-001 is an ongoing phase I/II, single-arm, open-label trial (NCT03157128). Eligible patients were ≥18 years old with diagnosis of advanced/metastatic RET fusion-positive solid tumor, RET-mutant medullary thyroid cancer, or other RET-activated tumors. In phase I, patients received selpercatinib 20 mg QD or 20-240 mg BID; patients in phase II received 160 mg BID. The analyzed population comprised all patients who received ≥1 selpercatinib dose and were followed up until data cutoff (January 13, 2023).</p><p><strong>Results: </strong>For the 837 patients, median follow-up was 45.4 months (95% CI, 44.5-46.6); median time on treatment was 30.1 months (range 0.1-66.8). Grade ≥3 treatment-emergent AEs (TEAEs) were reported in 76.2% of patients; most common events were hypertension (19.7%), ALT increased (11.8%), and hyponatremia (9.2%). Serious TEAEs were reported in 51.4% of patients. Most frequently reported any-grade AEs at <6 months of treatment were fatigue (36.6%), dry mouth (32.8%), and ALT increased (30.5%); at ≥24 months of treatment, these were edema (63.2%), diarrhea (60.7%), and fatigue (53.0%). Selpercatinib-related TEAEs leading to reduced dosage were reported in 39.3%, those leading to treatment interruption were reported in 47.1%, and those leading to discontinuation were reported in 4.3% of patients.</p><p><strong>Conclusion: </strong>Long-term treatment with selpercatinib is feasible. AEs are manageable with dose modifications, allowing most patients to continue safely on therapy.</p>\",\"PeriodicalId\":54686,\"journal\":{\"name\":\"Oncologist\",\"volume\":\" \",\"pages\":\"1068-1078\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-12-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630769/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oncologist\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/oncolo/oyae282\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncologist","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/oncolo/oyae282","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Long-term safety of selpercatinib for Rearranged during transfection (RET)-activated advanced solid tumors in LIBRETTO-001: differing patterns of adverse events over time.
Background: Selpercatinib is a selective RET inhibitor approved for treatment of RET-activated cancers. Adverse events (AEs) are manageable with dose modifications. This post hoc analysis characterized selpercatinib's clinical safety profile after long-term follow-up in the safety population of LIBRETTO-001.
Patients and methods: LIBRETTO-001 is an ongoing phase I/II, single-arm, open-label trial (NCT03157128). Eligible patients were ≥18 years old with diagnosis of advanced/metastatic RET fusion-positive solid tumor, RET-mutant medullary thyroid cancer, or other RET-activated tumors. In phase I, patients received selpercatinib 20 mg QD or 20-240 mg BID; patients in phase II received 160 mg BID. The analyzed population comprised all patients who received ≥1 selpercatinib dose and were followed up until data cutoff (January 13, 2023).
Results: For the 837 patients, median follow-up was 45.4 months (95% CI, 44.5-46.6); median time on treatment was 30.1 months (range 0.1-66.8). Grade ≥3 treatment-emergent AEs (TEAEs) were reported in 76.2% of patients; most common events were hypertension (19.7%), ALT increased (11.8%), and hyponatremia (9.2%). Serious TEAEs were reported in 51.4% of patients. Most frequently reported any-grade AEs at <6 months of treatment were fatigue (36.6%), dry mouth (32.8%), and ALT increased (30.5%); at ≥24 months of treatment, these were edema (63.2%), diarrhea (60.7%), and fatigue (53.0%). Selpercatinib-related TEAEs leading to reduced dosage were reported in 39.3%, those leading to treatment interruption were reported in 47.1%, and those leading to discontinuation were reported in 4.3% of patients.
Conclusion: Long-term treatment with selpercatinib is feasible. AEs are manageable with dose modifications, allowing most patients to continue safely on therapy.
期刊介绍:
The Oncologist® is dedicated to translating the latest research developments into the best multidimensional care for cancer patients. Thus, The Oncologist is committed to helping physicians excel in this ever-expanding environment through the publication of timely reviews, original studies, and commentaries on important developments. We believe that the practice of oncology requires both an understanding of a range of disciplines encompassing basic science related to cancer, translational research, and clinical practice, but also the socioeconomic and psychosocial factors that determine access to care and quality of life and function following cancer treatment.