Ramucirumab in elderly patients with hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib in REACH and REACH-2

Kudo, M.; Galle, P. R.; Llovet, J. M.; Finn, R. S.; Vogel, A.; Motomura, K.; Assenat, E.; Merle, P.; Brandi, G.; Daniele, B.; Okusaka, T.; Tomasek, J.; Borg, C.; Dadduzio, V.; Morimoto, M.; Pracht, M.; Jen, M. -H.; Drove Ubreva, N.; Widau, R. C.; Shinozaki, K.; Yoshikawa, R.; Zhu, A. X.

doi:10.1111/liv.14462

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.

Titolo:	Ramucirumab in elderly patients with hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib in REACH and REACH-2
Autore/i:	Kudo M.; Galle P. R.; Llovet J. M.; Finn R. S.; Vogel A.; Motomura K.; Assenat E.; Merle P.; Brandi G.; Daniele B.; Okusaka T.; Tomasek J.; Borg C.; Dadduzio V.; Morimoto M.; Pracht M.; Jen M. -H.; Drove Ubreva N.; Widau R. C.; Shinozaki K.; Yoshikawa R.; Zhu A. X.
Autore/i Unibo:	Kudo M. Galle P. R. Llovet J. M. Finn R. S. VOGEL, YANNICK ALEXANDER Motomura K. Assenat E. Merle P. BRANDI, GIOVANNI Daniele B. Okusaka T. Tomasek J. Borg C. Dadduzio V. Morimoto M. Pracht M. Jen M. -H. Drove Ubreva N. Widau R. C. Shinozaki K. Yoshikawa R. Zhu A. X. mostra contributor esterni nascondi contributor esterni
Anno:	2020
Rivista:	LIVER INTERNATIONAL
Digital Object Identifier (DOI):	http://dx.doi.org/10.1111/liv.14462
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.
Data stato definitivo:	2022-03-01T13:22:59Z
Appare nelle tipologie:	1.01 Articolo in rivista

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