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
3330 - Tumour-infiltrating lymphocytes and BRCA-like status in stage III breast cancer patients treated with intensified carboplatin-based chemotherapy
Presenter: Leonora De Boo
Session: Poster Display session 2
Resources:
Abstract
3971 - Unravelling the biological characteristics of MammaPrint extreme risk subgroups
Presenter: Rajith Bhaskaran
Session: Poster Display session 2
Resources:
Abstract
5871 - Residual Cancer burden as a prognostic factor in a large series of Neoadjuvant chemotherapy. Subgroup analysis per molecular surrogated subtypes
Presenter: Catalina Falo
Session: Poster Display session 2
Resources:
Abstract
5014 - Clinical validation of CanAssist Breast in a Spanish cohort
Presenter: Manjiri Bakre
Session: Poster Display session 2
Resources:
Abstract
2787 - Meta-analysis on association of pathological complete response with long-term survival outcomes in triple-negative breast cancer
Presenter: Peter A. Fasching
Session: Poster Display session 2
Resources:
Abstract
4301 - Immune infiltrate composition across intrinsic subtypes in hormone receptor (HR)+/HER2- early breast cancer (BC) enrolled in the prospective LETLOB trial
Presenter: Gaia Griguolo
Session: Poster Display session 2
Resources:
Abstract
3205 - Frequency of germline mutations in women's cancer susceptibility genes in a large cohort of Chinese breast cancer patients
Presenter: Ning Liao
Session: Poster Display session 2
Resources:
Abstract
4091 - Triple blinded Prospective Study assessing the Impact of Genomics & Artificial Intelligence Watson For Oncology (WFO) on MDT’s Decision of Adjuvant Systemic Therapy for Hormone Receptor Positive Early Breast Carcinoma-
Presenter: Somashekhar Sampige Prasannakumar
Session: Poster Display session 2
Resources:
Abstract
4359 - Prognostic significance of Progesterone Receptor levels in luminal-like Her2- early Breast Cancer patients. A retrospective single Cancer Center analysis.
Presenter: Anna Diana
Session: Poster Display session 2
Resources:
Abstract
1369 - PAM50 HER2-enriched subtype and pathological complete response in HER2-positive early breast cancer: a meta-analysis
Presenter: Francesco Schettini
Session: Poster Display session 2
Resources:
Abstract