Abstract 1292P
Background
Selpercatinib (LOXO-292) is a selective RET inhibitor that has demonstrated robust and durable anti-tumor activity in RET-fusion positive NSCLC. 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; the December 2019 interim analysis are reported.
Methods
Patients with NSCLC completed the validated European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) prior to initiating study treatment and approximately every 8 weeks. All subscales are scored 0-100; higher scores indicate better functioning or more severe symptoms. A clinically meaningful difference (CMD) was pre-defined as ≥10-point change from baseline. Results are reported descriptively by cycle and as mean change from baseline; each patient was categorized as “improved” or “worsened” at each study visit if the CMD was met versus their baseline score.
Results
As of the database lock, 184 patients with NSCLC completed a baseline assessment; adherence was >85% at each scheduled visit. Baseline physical, emotional, cognitive and social subscales were >70 points. The mean baseline global health status was 61.5 (standard deviation, SD=23.6). The highest mean baseline symptom scores were fatigue (37.9, SD=26.0) and insomnia (28.1, SD=30.9). Mean post-baseline subscale scores reached CMD improvements among >30% of patients for physical function and 45% or more of patients for global health status and fatigue (Table of worsened and improved; unchanged not reported). Table: 1292P
| QLQ-C30, n (%) | Cycle 3 (n=159) | Cycle 5(n=134) | Cycle 7(n=110) | Cycle 9 (n=69) | Cycle 11(n=49) | |
| Physical Function | Improved | 51 (32.1) | 47 (35.1) | 37 (33.6) | 26 (37.7) | 21 (42.9) |
| Worsened | 20 (12.6) | 16 (11.9) | 13 (11.8) | 4 (5.8) | 5 (10.2) | |
| Global Health Status | Improved | 71 (45.5)a | 71 (54.2)b | 58 (53.2)c | 36 (53.7)d | 27 (55.1) |
| Worsened | 29 (18.6)a | 18 (13.7)b | 16 (14.7)c | 7 (10.4)d | 5 (10.2) | |
| Fatigue | Improved | 71 (44.9) | 67 (50.0) | 53 (48.2) | 33 (47.8) | 22 (44.9) |
| Worsened | 39 (24.7) | 26 (19.4) | 25 (22.7) | 18 (26.1) | 11 (22.4) | |
| Insomnia | Improved | 38 (23.9) | 39 (29.1) | 33 (30.0) | 19 (27.5) | 20 (40.8) |
| Worsened | 33 (20.8) | 20 (14.9) | 19 (17.3) | 9 (13.0) | 6 (12.2) |
an=156; bn=131; cn=109; dn=67
Conclusions
The proportion of patients reaching a CMD suggests a subset of patients with NSCLC who may have improvements on some PROs during therapy with selpercatinib. This is a preliminary interim analysis; 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
A.R. Minchom: Travel/Accommodation/Expenses: Loxo Oncology; Honoraria (self): Janssen; Honoraria (self): Faron Pharmaceuticals; Honoraria (self): Bayer Pharmaceuticals; Honoraria (self): Novartis Oncology; Honoraria (self): Merck. 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, Research grant/Funding (institution): Celgene; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy: Loxo Oncology; Advisory/Consultancy: Merck; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self): Roche; Advisory/Consultancy: Takeda; Research grant/Funding (institution): GlaxoSmithKline; Advisory/Consultancy: Merrimack. 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): Fugifilm; Research grant/Funding (institution): 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): Inhirbrx; 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, Research grant/Funding (institution): Helsinn. B. Robinson: Advisory/Consultancy: Loxo Oncology; Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai. L.J. Wirth: 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): Rakuten Medical. L.M. Hess: Full/Part-time employment: Eli Lilly and Company. X. Huang, J.F. Kherani, E. Olek: Full/Part-time employment: Loxo Oncology. C. McCoach: Honoraria (self), Research grant/Funding (institution): Novatis; Honoraria (self): Guardant Health; Advisory/Consultancy: Genentech; Research grant/Funding (institution): Revolution Medicines. All other authors have declared no conflicts of interest.