Abstract 1922P
Background
Selpercatinib (LOXO-292) is a highly selective and potent RET inhibitor that has demonstrated robust and durable anti-tumor activity in RET-mutant medullary thyroid cancer (MTC). Within the registrational trial, LIBRETTO-001 (NCT03157128), patients received twice daily oral selpercatinib in 28-day cycles. Descriptive PRO data were an exploratory endpoint of the trial; this work reports the December 2019 interim results related to diarrhea, a common disease-related event among patients with MTC.
Methods
Patients with MTC completed the validated European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and modified Systemic Therapy-Induced Diarrhea Assessment Tool (mSTIDAT). The QLQ-C30 was completed prior to initiating study treatment (baseline) and corresponding with radiologic disease assessments, approximately every 8 weeks, until end of study treatment. QLQ-C30 subscales are scored 0-100; higher scores indicate better functioning or more severe symptoms. A clinically meaningful difference was pre-defined as ≥10-point change from baseline.
Results
Data were available from the QLQ-C30 (n=192) and the mSTIDAT (n=123). Survey completion adherence was >85% at each scheduled visit. Mean QLQ-C30 baseline diarrhea was 40.1 (standard deviation, SD=38.2) and reduced by -23.2, -27.3, -27.9, -26.5, and -25.6 points at Cycles 3, 5, 7, 9, and 11 respectively. At baseline, 99 (80.5%) reported having diarrhea on the mSTIDAT; the majority of whom reported it as moderate or severe (48.5% and 25.3%, respectively). 53.2% patients with baseline diarrhea reported having no diarrhea by Cycle 3 (42/79). Of the 37 (46.8%) who continued to report diarrhea, 70.3% (26/37) reported its severity as minimal. More than 80% of patients who reported diarrhea reported a reduction in diarrhea (n=81, 81.8%) during the treatment period.
Conclusions
Most patients with MTC had diarrhea with moderate to high severity at baseline. Sustained reduction in rate and severity of diarrhea were observed during treatment with selpercatinib. Patients continue to be enrolled to LIBRETTO-001.
Clinical trial identification
NCT03157128.
Editorial acknowledgement
Legal entity responsible for the study
Loxo Oncology.
Funding
Loxo Oncology.
Disclosure
L.J. Wirth: Honoraria (self), Research grant/Funding (institution): Loxo Oncology; Honoraria (self): Bayer; Honoraria (self): Blueprint Medicine; Honoraria (self): Cue Biopharma; Honoraria (self): Eisai; Honoraria (self): Exelixis; Honoraria (self): Genentech; Honoraria (self): Eli Lilly and Company; Honoraria (self): Merck; Honoraria (self): Rakkuten Medical. B. Robinson: Advisory/Consultancy: Loxo Oncology; Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai. D.S.W. Tan: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Celgene; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy: Loxo Oncology; Honoraria (self): Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self): Roche; Advisory/Consultancy: Takeda; Research grant/Funding (institution): GlaxoSmithKline; Advisory/Consultancy: Merrimack. C. McCoach: Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self): Guardant Health; Advisory/Consultancy: Genentech; Research grant/Funding (institution): Revolution Medicines. L.M. Hess: Full/Part-time employment: Eli Lilly and Company. X. Huang, J.F. Kherani, E. Olek: Full/Part-time employment: Loxo Oncology. V. Subbiah: Advisory/Consultancy, Research grant/Funding (institution): Loxo Oncology; Research grant/Funding (institution): Roche/Genentech; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Nanocarrier; Research grant/Funding (institution): Vegenics; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Northwest Biotherapeutics; Research grant/Funding (institution): Berghealth; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Fujifilm; Research grant/Funding (institution), Travel/Accommodation/Expenses: PharmaMar; Research grant/Funding (institution): D3; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Multivir; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Alfa-sigma; Research grant/Funding (institution): Agensys; Research grant/Funding (institution): Boston Biomedical; Research grant/Funding (institution): Idera Pharma; Research grant/Funding (institution): Inhibrx; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Blueprint Medicines; Advisory/Consultancy, Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Altum; Research grant/Funding (institution): Dragonfly Therapeutics; Research grant/Funding (institution): Takeda; Advisory/Consultancy: Helsinn. All other authors have declared no conflicts of interest.