Abstract 1758
Background
REACH (NCT01140347) and REACH-2 (NCT02435433) were two global, randomized, double-blind, placebo (PL)-controlled multicenter, phase 3 studies of RAM vs PL in patients with HCC after prior sorafenib. REACH-2 confirmed overall survival (OS) benefit of RAM for patients with baseline AFP ≥400 ng/mL, consistent with results in a prespecified subgroup of patients in REACH with AFP ≥400 ng/mL.
Methods
Post-hoc pooled analyses were performed to examine efficacy and safety in three age subgroups (<65, ≥65-<75, ≥75 years). In pooled population of patients from REACH (AFP ≥400 ng/mL) and REACH-2, Kaplan-Meier method and Cox proportional hazards regression were performed for OS, progression-free survival (PFS), and deterioration of FHSI-8 total score by three points or more. The incidence of adverse events (AEs) is also reported by age subgroups.
Results
Both intention-to-treat populations were pooled (542 patients in total). Within each age subgroup, baseline characteristics between treatment arms were similar. Patients of < 65 years showed a higher incidence of hepatitis B, extrahepatic spread, and a higher AFP level when compared with patients in older age subgroups across treatment arms. Efficacy outcomes are summarized in the table. Safety profiles of RAM were comparable between <65 and ≥65-<75 age subgroups. The incidence of ≥Grade 3 treatment-emergent AEs was higher in RAM arm than PL arm in ≥ 75 age subgroup (e.g. hypertension and fatigue). A trend toward a delay in the deterioration of symptoms in FHSI-8 for RAM arm was observed in all age subgroups.Table:
757P
Age (years) | Treatment | Number of patients (ITT population) | Median OS (months) | OS hazard ratio (95% CI) | Median PFS (months) | PFS hazard ratio (95% CI) | Number of patients (Safety population) | Median relative dose intensity % | |
---|---|---|---|---|---|---|---|---|---|
REACH (AFP ≥400ng/mL) + REACH-2 | <65 | RAM + BSC | 171 | 8.18 | 0.716 (0.556, 0.922) | 2.73 | 0.616 (0.483, 0.786) | 171 | 98.56 |
PL + BSC | 131 | 4.76 | 1.45 | 128 | 99.80 | ||||
≥65-<75 | RAM + BSC | 93 | 7.62 | 0.593 (0.413, 0.851) | 2.78 | 0.552 (0.390, 0.782) | 93 | 98.03 | |
PL + BSC | 67 | 5.22 | 1.84 | 67 | 99.96 | ||||
≥75 | RAM + BSC | 52 | 8.87 | 0.641 (0.390, 1.054) | 4.17 | 0.477 (0.291, 0.781) | 52 | 97.75 | |
PL + BSC | 28 | 6.31 | 1.64 | 28 | 98.57 |
Conclusions
Efficacy and safety profiles of RAM observed in each age subgroup were consistent with those in the entire population. This exploratory subgroup analysis supports the use of RAM for the treatment of HCC with elevated AFP, irrespective of age.
Clinical trial identification
REACH (NCT01140347); REACH-2 (NCT02435433).
Editorial acknowledgement
Legal entity responsible for the study
Eli Lilly and Company.
Funding
Eli Lilly and Company.
Disclosure
M. Kudo: Honoraria (self), Research grant / Funding (self): Bayer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Eisai; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): MSD; Advisory / Consultancy: BMS; Advisory / Consultancy: Ono; Advisory / Consultancy: Eli Lilly; Research grant / Funding (self): Chugai; Research grant / Funding (self): Otsuka; Research grant / Funding (self): Takeda; Research grant / Funding (self): Taiho; Research grant / Funding (self): Daiichi Sankyo; Research grant / Funding (self): AbbVie; Research grant / Funding (self): Astellas; Research grant / Funding (self): EA Pharma; Research grant / Funding (self): Gilead. P.R. Galle: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Sirtex; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen. K. Motomura: Honoraria (self): Eisai. E. Assenat: Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Terasphere; Honoraria (self), Advisory / Consultancy: Sirtex; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Servier. P. Merle: Advisory / Consultancy: Bayer; Advisory / Consultancy: Ipsen/Exelixis; Advisory / Consultancy: BMS; Advisory / Consultancy, Research grant / Funding (self): Onxeo; Advisory / Consultancy: MSD; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Eisai; Advisory / Consultancy: Roche. G. Brandi: Advisory / Consultancy: Eli Lilly and Company. B. Daniele: Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self): IPSEN; Honoraria (self): EISAI; Honoraria (self): Eli Lilly; Honoraria (self): MSD; Honoraria (self): Merck Kga; Honoraria (self): Sanofi; Honoraria (self): Incyte. T. Okusaka: Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy: Taiho; Honoraria (self), Research grant / Funding (self): Eli Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Dainippon Sumitomo; Honoraria (self), Research grant / Funding (self): Bayer; Honoraria (self), Research grant / Funding (self): Yakult Honsha; Honoraria (self): Nobelpharma; Honoraria (self): Fujifilm; Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self), Research grant / Funding (self): Ono; Honoraria (self): EA Pharma; Honoraria (self), Research grant / Funding (self): Celgene; Honoraria (self), Research grant / Funding (self): Chugai; Honoraria (self), Research grant / Funding (self): Eisai; Honoraria (self), Research grant / Funding (self): Pfizer; Honoraria (self): Teijin; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo; Honoraria (self): Shire; Honoraria (self): Takara Bio; Honoraria (self): AbbVie. J. Tomasek: Honoraria (self): Eli Lilly and Company. C. Borg: Advisory / Consultancy: Roche; Advisory / Consultancy: Servier; Advisory / Consultancy: Bayer. V. Zagonel: Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy: Celgene; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Janssen. R.S. Finn: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche/Genentech; Honoraria (self), Advisory / Consultancy: Eisai. J. Llovet: Honoraria (self): Exelixis; Honoraria (self): Merck; Honoraria (self): Glycotest; Honoraria (self): Navigant; Honoraria (self): Leerink Swann Llc; Honoraria (self): Midatech ltd; Honoraria (self): Fortress Biotech inc; Honoraria (self): Spring bank pharma; Honoraria (self): Nucleix. G. Homma: Full / Part-time employment: Eli Lilly Japan K.K. M. Jen: Full / Part-time employment: Eli Lilly and Company. K. Shinozaki: Full / Part-time employment: Eli Lilly Japan K.K. R. Yoshikawa: Full / Part-time employment: Eli Lilly Japan K.K. A.X. Zhu: Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.
Resources from the same session
4732 - Progesterone Receptor Isoform Ratio Dictates Antiprogestins/Progestins Effects on Metastatic Breast Cancer Models
Presenter: Maria Abascal
Session: Poster Display session 2
Resources:
Abstract
5737 - PAM50 and CGH-array genomic characterization of HER2-Equivocal Breast Cancers defined by the 2018 ASCO/CAP recommendations.
Presenter: Carine Ngo
Session: Poster Display session 2
Resources:
Abstract
1096 - OncotypeDX® predictive nomogram for recurrence score output: a machine learning system based on quantitative immunochemistry analysis - ADAPTED01
Presenter: Fabio Marazzi
Session: Poster Display session 2
Resources:
Abstract
5426 - Geriatric parameters predict both disease-related and patient-reported outcomes in older patients with breast cancer
Presenter: Willeke van der Plas-Krijgsman
Session: Poster Display session 2
Resources:
Abstract
5865 - Patients with a 21-gene assay in South East London differ from the TAILORx trial population
Presenter: Charalampos Gousis
Session: Poster Display session 2
Resources:
Abstract
1312 - Predictive tools in adjuvant breast cancer – what is the standard of evidence supporting their utility? A literature review examining validation of Adjuvant!, Cancermath and NHS Predict
Presenter: Alice Loft
Session: Poster Display session 2
Resources:
Abstract
2445 - Oncologic outcome of invasive lobular carcinoma: Is it different from that of invasive ductal carcinoma?
Presenter: Hee Jun Choi
Session: Poster Display session 2
Resources:
Abstract
2476 - Pathologic response and survival efficacy in patients with initial nodal involvement after neoadjuvant chemotherapy in early breast cancer
Presenter: SERAFIN MORALES Murillo
Session: Poster Display session 2
Resources:
Abstract
3761 - Chemotherapy-induced amenorrhea: prognostic impact on premenopausal Egyptian patients with breast cancer
Presenter: Khaled Abdel Karim
Session: Poster Display session 2
Resources:
Abstract
4687 - Predicting the presence of breast cancer using circulating small RNA in the serum
Presenter: Yumiko Koi
Session: Poster Display session 2
Resources:
Abstract