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
3668 - Patient Demographics and Management Landscape of Metastatic Colorectal Cancer in the Third Line Setting: real-world data in an Australian Population
Presenter: Sandy Tun Min
Session: Poster Display session 2
Resources:
Abstract
3907 - Exploration of efficacious alternative regorafenib regimens to manage hand-foot-skin-reaction (HFSR)
Presenter: Axel Grothey
Session: Poster Display session 2
Resources:
Abstract
3958 - Quality of Life (QoL) in Metastatic Colorectal Cancer (mCRC) in the Real World: Final Results of a European Survey
Presenter: Zorana Maravic
Session: Poster Display session 2
Resources:
Abstract
3563 - BISQUIT: A Randomized Phase II Study of the Administration of Prebiotics and Probiotics During Definitive Treatment With Chemotherapy-radiotherapy for Patients With Squamous Cell Carcinoma of the Anal Canal
Presenter: Rachel Riechelmann
Session: Poster Display session 2
Resources:
Abstract
1184 - iSCORE: Immunotherapy Sequencing in COlon and REctal Cancer
Presenter: Fiona Turkes
Session: Poster Display session 2
Resources:
Abstract
3346 - Phase II study of preoperative (PREOP) chemoradiotherapy (CTRT) plus avelumab (AVE) in patients (PTS) with locally advanced rectal cancer (LARC): The AVANA Study
Presenter: Lisa Salvatore
Session: Poster Display session 2
Resources:
Abstract
3895 - A phase II study of capecitabine plus concomitant radiation therapy followed by durvalumab (MEDI4736) as preoperative treatment in rectal cancer: PANDORA study.
Presenter: Maria Aurelia Barbera
Session: Poster Display session 2
Resources:
Abstract
2012 - Open Label Phase III Study of Arfolitixorin vs. Leucovorin in mFOLFOX-6 for First Line Treatment of Metastatic Colorectal Cancer: AGENT
Presenter: Josep Tabernero
Session: Poster Display session 2
Resources:
Abstract
2198 - SOLSTICE, a phase 3, randomized, open label study of trifluridine/tipiracil+bevacizumab (bev) versus capecitabine+bev for the 1L treatment of patients with unresectable metastatic colorectal cancer (mCRC) who are not candidates for intensive therapy
Presenter: Thierry Andre
Session: Poster Display session 2
Resources:
Abstract
2921 - A Phase Ib/ II Trial to Assess the Safety and Efficacy of CXD101 in Combination with the PD-1 Inhibitor Nivolumab in Patients with Metastatic, Previously-Treated, Microsatellite-Stable (MSS) Colorectal Carcinoma (short title CAROSELL)
Presenter: Mark Saunders
Session: Poster Display session 2
Resources:
Abstract