Masatoshi Kudo1, Peter R Galle2, Josep M Llovet3,4, Richard S Finn5, Arndt Vogel6, Kenta Motomura7, Eric Assenat8, Philippe Merle9, Giovanni Brandi10, Bruno Daniele11, Takuji Okusaka12, Jiří Tomášek13, Christophe Borg14, Vincenzo Dadduzio15, Manabu Morimoto16, Marc Pracht17, Min-Hua Jen18, Nora Drove Ubreva19, Ryan C Widau20, Kenta Shinozaki19, Reigetsu Yoshikawa19, Andrew X Zhu21. 1. Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan. 2. Department of Internal Medicine, Mainz University Medical Center, Mainz, Germany. 3. Translational Research in Hepatic Oncology Group, Liver Unit, IDIBAPS, Hospital Clinic Barcelona, University of Barcelona, Barcelona, Catalonia, Spain. 4. Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 5. Department of Medicine, Division of Hematology/Oncology, Geffen School of Medicine at UCLA, Los Angeles, CA, USA. 6. Department of Hepatology, Gastroenterology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany. 7. Department of Hepatology, Aso Iizuka Hospital, Fukuoka, Japan. 8. Department of Medical Oncology, CHU de Montpellier, Montpellier, France. 9. Hepatology and Gastroenterology Unit, Croix-Rousse Hospital, Northern Lyon Hospital Group, Lyon, France. 10. Department of Experimental, Diagnostic and Speciality Medicicne, University Hospital S.Orsola-Malpighi, Bologna, Italy. 11. Department of Oncology, Azienda Ospedaliera Gaetano Rummo, Benevento, Italy. 12. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. 13. Department of Complex Oncology Care, Masaryk Memorial Cancer Institute, Masaryk University, Brno, Czech Republic. 14. Department of Medical Oncology, University Hospital of Besançon, Besançon, France. 15. Department of Clinical and Experimental Oncology, Medical Oncology Unit-1, Veneto Institute of Oncology (IOV) - IRCCS, Padua, Italy. 16. Department of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama, Japan. 17. Department of Medical Oncology, Centre Eugène Marquis, Rennes, France. 18. Global Statistical Sciences, Eli Lilly and Company, Surrey, UK. 19. Medicines Development Unit Japan, Eli Lilly Japan K.K, Kobe, Japan. 20. Oncology, Eli Lilly and Company, Indianapolis, IN, USA. 21. Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Abstract
BACKGROUND & AIMS: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with alpha-fetoprotein (AFP) ≥400 ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥ 400 ng/mL by three prespecified age subgroups (<65, ≥65 to <75 and ≥75 years). METHODS: Individual patient data were pooled from REACH (baseline AFP ≥400 ng/mL) and REACH-2. Kaplan-Meier and Cox proportional hazards regression methods (stratified by study) assessed OS, progression-free survival (PFS), time to progression (TTP) and patient-reported outcomes (Functional Hepatobiliary System Index-8 [FHSI-8] score). RESULTS: A total of 542 patients (<65 years: n = 302; ≥65 to <75 years: n = 160; ≥75 years: n = 80) showed similar baseline characteristics between ramucirumab and placebo. Older subgroups had higher hepatitis C and steatohepatitis incidences, and lower AFP levels, than the <65 years subgroup. Ramucirumab prolonged OS in patients <65 years (hazard ratio [HR], 0.753; 95% CI 0.581-0.975), ≥65 to <75 years (0.602; 0.419-0.866) and ≥75 years (0.709; 0.420-1.199), PFS and TTP irrespective of age. Ramucirumab showed similar overall safety profiles across subgroups, with a consistent median relative dose intensity ≥97.8%. A trend towards a delay in symptom deterioration in FHSI-8 with ramucirumab was observed in all subgroups. CONCLUSIONS: In this post-hoc analysis, ramucirumab showed a survival benefit across age subgroups with a tolerable safety profile, supporting its use in advanced HCC with elevated AFP, irrespective of age, including ≥75 years.
BACKGROUND & AIMS: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with alpha-fetoprotein (AFP) ≥400 ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥ 400 ng/mL by three prespecified age subgroups (<65, ≥65 to <75 and ≥75 years). METHODS: Individual patient data were pooled from REACH (baseline AFP ≥400 ng/mL) and REACH-2. Kaplan-Meier and Cox proportional hazards regression methods (stratified by study) assessed OS, progression-free survival (PFS), time to progression (TTP) and patient-reported outcomes (Functional Hepatobiliary System Index-8 [FHSI-8] score). RESULTS: A total of 542 patients (<65 years: n = 302; ≥65 to <75 years: n = 160; ≥75 years: n = 80) showed similar baseline characteristics between ramucirumab and placebo. Older subgroups had higher hepatitis C and steatohepatitis incidences, and lower AFP levels, than the <65 years subgroup. Ramucirumab prolonged OS in patients <65 years (hazard ratio [HR], 0.753; 95% CI 0.581-0.975), ≥65 to <75 years (0.602; 0.419-0.866) and ≥75 years (0.709; 0.420-1.199), PFS and TTP irrespective of age. Ramucirumab showed similar overall safety profiles across subgroups, with a consistent median relative dose intensity ≥97.8%. A trend towards a delay in symptom deterioration in FHSI-8 with ramucirumab was observed in all subgroups. CONCLUSIONS: In this post-hoc analysis, ramucirumab showed a survival benefit across age subgroups with a tolerable safety profile, supporting its use in advanced HCC with elevated AFP, irrespective of age, including ≥75 years.
Authors: Rocio I R Macias; Maria J Monte; Maria A Serrano; Jesús M González-Santiago; Isabel Martín-Arribas; André L Simão; Rui E Castro; Javier González-Gallego; José L Mauriz; Jose J G Marin Journal: Aging (Albany NY) Date: 2021-10-11 Impact factor: 5.682