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
2376 - Patient Reported Outcomes (PRO) in patients (pts) with HER2- advanced breast cancer (ABC) and a germline BRCA1/2 mutation (gBRCAm) receiving talazoparib (TALA) vs physician’s choice chemotherapy (PCT) in the EMBRACA trial: A focus on subgroups with/ without visceral disease
Presenter: Johannes Ettl
Session: Poster Display session 2
Resources:
Abstract
4874 - Complete Responses in Patients With 2nd-Line or Greater Metastatic Triple-Negative Breast Cancer (TNBC) Following First-in-Human Immunotherapy Combining NK and T Cell Activation with Off-the-Shelf High-Affinity CD16 NK Cell Line (haNK)
Presenter: Chaitali Nangia
Session: Poster Display session 2
Resources:
Abstract
4362 - Reproducibility and concordance of 4 clinically developed programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assays in triple-negative breast cancer (TNBC)
Presenter: Aurelia Noske
Session: Poster Display session 2
Resources:
Abstract
4528 - Systemic Therapy in 2nd-Line Metastatic Triple Negative Breast Cancer (mTNBC): A Systematic Literature Review (SLR) and Meta-Analysis (MA) of Efficacy
Presenter: Peter Kaufman
Session: Poster Display session 2
Resources:
Abstract
4112 - Cisplatin given at three divided doses for three consecutive days in metastatic breast cancer: an alternative schedule for one full dose with comparable efficacy but less CINV and hypomagnesaemia
Presenter: Yang Chen
Session: Poster Display session 2
Resources:
Abstract
5699 - Patterns and predictors of first-line (1L) taxane use in US patients with metastatic triple-negative breast cancer (mTNBC)
Presenter: Joyce O’Shaughnessy
Session: Poster Display session 2
Resources:
Abstract
1931 - Maintenance Chemotherapy is effective in Patients with Metastatic Triple Negative Breast Cancer After First-line Platinum-based Chemotherapy
Presenter: Jian Zhang
Session: Poster Display session 2
Resources:
Abstract
4696 - Using the Patient-Reported Outcomes Measurement Information System (PROMIS) to investigate symptom burden enrichment in Stage IV patients at an academic center
Presenter: Madeline Matthys
Session: Poster Display session 2
Resources:
Abstract
4582 - Measures of functional status in adults aged ≥70 years with advanced breast cancer (ABC) receiving palbociclib (PAL) combination therapy in POLARIS
Presenter: Meghan Karuturi
Session: Poster Display session 2
Resources:
Abstract
3565 - Real-World 1-Year Survival Analysis of Patients with Metastatic Breast Cancer with Liver or Lung Metastasis Treated with Eribulin, Gemcitabine or Capecitabine
Presenter: Shayma Kazmi
Session: Poster Display session 2
Resources:
Abstract