Abstract 1010P
Background
REG is approved for pts with uHCC previously treated with sorafenib (SOR). The ongoing REFINE study is evaluating REG in pts with uHCC in real-world practice. In this IA, we analyzed initial dosing and pt characteristics in REFINE.
Methods
REFINE includes pts with uHCC for whom a decision to treat with REG was made by the treating physician prior to enrollment according to the local health authority approved label. The primary aim is to assess treatment-emergent adverse events (TEAEs; NCI-CTCAE v4.03). Secondary endpoints include overall survival (OS). A planned IA was performed when the first 500 pts had been observed for ≥4 months.
Results
Of 498 pts treated, 84% were male, median age was 66 years (range 21–90); 82%/5% had ECOG performance status (PS) 0–1/≥2 (missing 13%) at study entry. The initial daily dose of REG was 160 mg in 57% of pts (n=286), 120 mg in 13% (n=63), 80 mg in 28% (n=141), and 40 mg in 2% (n=8). Median age and proportion of pts ≥65 years were similar across initial dose groups (Table). Pts initiating at <160 mg tended to have Child–Pugh B liver function and worse ECOG PS vs those starting at 160 mg. Among pts who received prior SOR (n=482), 59% (n=282) started REG at 160 mg, 12% (n=59) at 120 mg, and 28% (n=133) at 80 mg. Of those, a higher proportion starting REG at 160 mg vs <160 mg had a last daily SOR dose of 800 mg (51% vs 36%); a higher proportion starting REG at 80 mg (13%) vs 160 mg (4%) or 120 mg (5%) had discontinued SOR due to a TEAE. Overall (n=498), the most frequent TEAEs (any grade) were hand–foot skin reaction (30%), diarrhea (21%), fatigue (16%), and decreased appetite (14%). Median OS overall was 13.2 months (95% CI 11.4, 16.3; censored: n=343).
Conclusions
This large observational study is assessing the real-world pt characteristics, dosing practices, and sequencing of REG in pts with uHCC. Results of the IA show that most pts initiated REG at the label dose of 160 mg daily. Table: 1010P
| REG initial daily dose* | |||
| 160 mg (n=286) | 120 mg (n=63) | 80 mg (n=141) | |
| Region, % | |||
| Asia | 68 | 78 | 35 |
| Non-Asia | 32 | 22 | 65 |
| Median age (range), years | 66 (21–90) | 65 (29–87) | 66 (30–88) |
| Age category, % | |||
| <65 years | 46 | 48 | 44 |
| ≥65 years | 54 | 52 | 56 |
| Time between initial uHCC diagnosis and start of REG, median (IQR), months | 26 (11–55) | 25 (12–51) | 22 (10–41) |
| Child–Pugh class, % | |||
| A | 75 | 62 | 51 |
| B | 7 | 16 | 18 |
| C | 1 | 0 | 1 |
| Not evaluable | 1 | 3 | 1 |
| Missing | 16 | 19 | 29 |
| ECOG PS, % | |||
| 0 | 48 | 41 | 30 |
| 1 | 38 | 44 | 43 |
| 2–4 | 4 | 6 | 7 |
| Missing | 10 | 8 | 21 |
| Metastases present, % | 60 | 70 | 54 |
| Vascular invasion present, % | 31 | 33 | 35 |
| Received prior SOR (at any time), % | 99 | 94 | 94 |
| Median duration of treatment (IQR), months | 3.7 (1.9–8.5) | 4.0 (2.2–9.4) | 3.8 (1.9–9.2) |
*8 pts who initiated at 40 mg are not shown.
Clinical trial identification
NCT03289273.
Editorial acknowledgement
Editorial assistance was provided by Jennifer Tobin of OPEN Health Medical Communications (Choice), with financial support from Bayer.
Legal entity responsible for the study
Bayer.
Funding
Bayer.
Disclosure
P. Merle: Advisory/Consultancy, Research grant/Funding (self): Onxeo; Advisory/Consultancy, Research grant/Funding (self): Ipsen; Advisory/Consultancy: Roche; Advisory/Consultancy: Bayer; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Lilly ; Advisory/Consultancy: BMS; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Merck; Advisory/Consultancy: Eisai. H.Y. Lim: Advisory/Consultancy: Bayer; Advisory/Consultancy: Eisai; Advisory/Consultancy: BMS; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Roche; Advisory/Consultancy: AstraZeneca. R.S. Finn: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: CStone Pharmaceuticals; Advisory/Consultancy: Exilixis; Advisory/Consultancy: Eisai; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Roche. M. Ikeda: Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self): Taiho; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Yakult; Honoraria (self): Teijin; Honoraria (self), Advisory/Consultancy: Servier; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Honoraria (self), Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Ono; Research grant/Funding (institution): BMS; Research grant/Funding (institution): MSD; Research grant/Funding (institution): J-Pharma; Research grant/Funding (institution): Aslan; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Merck Serona; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Pfizer. M. Kudo: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Eisai; Honoraria (self): Bayer; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self): Lilly; Advisory/Consultancy: Ono Pharmaceutical; Advisory/Consultancy: Roche; Advisory/Consultancy: AstraZeneca; Research grant/Funding (self): Gilead Sciences; Research grant/Funding (self): Sumitomo Dainippon Pharma; Research grant/Funding (self): Takeda; Research grant/Funding (self): Otsuka; Research grant/Funding (self): EA Pharma; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Taiho. C. Frenette: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer. G. Masi: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer. Y.J. Kim: Honoraria (self): Eisai; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): BMS; Honoraria (self), Research grant/Funding (self): BTG; Honoraria (self): Bayer; Honoraria (self): MSD; Advisory/Consultancy, Research grant/Funding (self): Gilead Sciences; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Roche. R. Gerolami: Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Travel/Accommodation/Expenses: Roche. M. Kurosaki: Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer. H-J. Klümpen: Advisory/Consultancy: Ipsen; Research grant/Funding (institution): Bayer. H. Zebger-Gong: Full/Part-time employment: Bayer. S. Fiala-Buskies: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bayer. K. Ozgurdal: Full/Part-time employment: Bayer. All other authors have declared no conflicts of interest.