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
3608 - Prognostic impact of Body Mass Index (BMI) on overall survival in patients with metastatic breast cancer
Presenter: Khalil SALEH
Session: Poster Display session 2
Resources:
Abstract
2686 - Clinicopathological characteristics, survival and prognostic factors of breast cancer-related microangiopathic haemolytic anemia: a multicenter study
Presenter: Marion Alhenc Gelas
Session: Poster Display session 2
Resources:
Abstract
1565 - Metabolic tumor volume by 18F-FDG PET/CT is an independent prognostic factor in metastatic breast cancer
Presenter: Heekyung Ahn
Session: Poster Display session 2
Resources:
Abstract
4498 - Patient Preferences for breast cancer treatments: A Discrete Choice Experiment from four European countries
Presenter: Thomais Konstantopoulou
Session: Poster Display session 2
Resources:
Abstract
1423 - Palbociclib plus fulvestrant as second- or later-line therapy for patients with locally advanced, inoperable or metastatic HR+/HER2- breast cancer in Germany: Interim results of the INGE-B phase 2 study
Presenter: Diana Lüftner
Session: Poster Display session 2
Resources:
Abstract
2284 - Ventriculoperitoneal Shunt for CNS Metastasis in Breast Cancer: Clinical Outcomes Based on Intrinsic Subtype
Presenter: Hee Kyung Kim
Session: Poster Display session 2
Resources:
Abstract
4598 - Administration of chemotherapy for metastatic breast cancer near the end of life: a population registry study
Presenter: Luisa Edman Kessler
Session: Poster Display session 2
Resources:
Abstract
5706 - Prognostic value of histological growth pattern in patients operated for breast cancer liver metastases
Presenter: Ali Bohlok
Session: Poster Display session 2
Resources:
Abstract
1697 - Illness perceptions, quality of life and mood in metastatic breast cancer patients
Presenter: Isabel Domingues
Session: Poster Display session 2
Resources:
Abstract
1935 - Multidisciplinary Treatments Increases Overall Survival in Patients with Newly Diagnosed Stage IV Breast Cancer:An Analysis of 2010–2014 SEER Data
Presenter: Jian Zhang
Session: Poster Display session 2
Resources:
Abstract