Abstract 2150
Background
A decrease in AFP level during treatment has been associated with improved overall survival (OS) in patients with HCC. In the phase 3 RESORCE trial (NCT01774344), the multikinase inhibitor regorafenib significantly improved OS versus placebo in patients with HCC and disease progression on sorafenib. We analyzed OS in patients who had an AFP response in RESORCE.
Methods
Patients with Barcelona Clinic Liver Cancer stage B or C HCC, Child -Pugh A liver function, ECOG performance status 0 − 1, and documented radiologic progression on prior sorafenib were randomized 2:1 to regorafenib 160 mg/day (n = 379) or placebo (n = 194) for Weeks 1-3 of each 4-week cycle. Serum AFP levels were assessed at baseline, every 4 weeks during treatment, and at the end of treatment. Patients who had a baseline AFP ≥20 ng/mL and an AFP measurement at the start of Cycle 3 were evaluable for AFP response, defined as a decrease of ≥ 20% in AFP level from baseline at the start of Cycle 3.
Results
Overall, 232 of the 573 randomized patients fulfilled the above criteria and were included in the analysis. Patients with an AFP response had a median OS from randomization of 13.8 months vs 8.9 months in those without an AFP response (Table). The rate of AFP response was 46% (77/168) in the regorafenib group and 11% (7/64) in the placebo group. Among regorafenib-treated patients, the median OS was 13.8 months in patients with an AFP response vs 9.8 months in those without an AFP response. A landmark analysis of OS from the start of Cycle 3 showed that the hazard ratios for AFP response vs no response were 0.57 (95% CI 0.40, 0.82) in the regorafenib and placebo arms combined and 0.72 (95% CI 0.48, 1.08) for patients in the regorafenib arm.Table:
755P
Regorafenib + /placebo arms combined | Regorafenib arm | |||
---|---|---|---|---|
(n = 232) | (n = 168) | |||
AFP response (n = 84) | No AFP response (n = 148) | AFP response (n = 77) | No AFP response (n = 91) | |
Median OS (95% CI) from randomization, months | 13.8 (11.8, 16.5) | 8.9 (8.0, 9.7) | 13.8 (11.7, 16.5) | 9.8 (8.2, 14.2) |
HR (95% CI) AFP response yes/no | 0.57 (0.40, 0.82) | 0.72 (0.48, 1.07) | ||
CI, confidence interval; HR, hazard ratio. |
Conclusions
In this exploratory analysis of RESORCE, an AFP response with regorafenib was associated with improved OS.
Clinical trial identification
NCT01774344.
Editorial acknowledgement
Jennifer Tobin of OPEN Health Medical Communications (London, UK), with financial support from Bayer.
Legal entity responsible for the study
Bayer.
Funding
Bayer.
Disclosure
J. Bruix: Honoraria (self): Bayer; BTG; Eisai; Ipsen; Sirtex; Terumo; Advisory / Consultancy: AbbVie; Adaptimmune; Arqule; Astra-Medimmune; Basilea; Bayer; Bio-Alliance; Bristol-Myers Squibb; BTG; Eisai; Gilead; Incyte; Ipsen; Kowa; Lilly; Merck Sharp & Dohme; Nerviano; Novartis; Quirem; Roche; Sanofi Aventis; Sirtex; Terumo; Research grant / Funding (institution): Bayer; BTG. M. Reig: Honoraria (self): AstraZeneca; Bayer; Bristol-Myers Squibb; BTG; Gilead; Ipsen; Lilly; Advisory / Consultancy: AstraZeneca; Bayer; Bristol-Myers Squibb; Ipsen; Lilly; Roche; Research grant / Funding (institution): Bayer; Travel / Accommodation / Expenses: Bayer; Bristol-Myers Squibb; Gilead; Ipsen; Lilly. P. Merle: Advisory / Consultancy: AstraZeneca; Bayer; Bristol-Myers Squibb; Eisai; Exelixis; Ipsen; Merck Sharp & Dohme; Onxeo; Roche. M. Kudo: Honoraria (self): Bayer; Eisai; Merck Sharp & Dohme; Advisory / Consultancy: Bayer; Bristol-Myers Squibb; Eisai; Merck Sharp & Dohme; Ono Pharmaceutical; Research grant / Funding (institution): AbbVie; Astellas Pharma; Bristol-Myers Squibb; Chugai; Daiichi Sankyo; EA Pharma; Eisai; Gilead; Medico’s Hirata; Otsuka; Taiho; Takeda. G. Meinhardt: Shareholder / Stockholder / Stock options: Bayer; Full / Part-time employment: Bayer. M. Zhang: Shareholder / Stockholder / Stock options: Bayer; Full / Part-time employment: Bayer. K. Ozgurdal: Full / Part-time employment: Bayer.
Resources from the same session
4390 - Phase II trial of trifluridine/tipiracil (TAS-102) in patients with advanced refractory biliary tract cancer (BTC)
Presenter: Sakti Chakrabarti
Session: Poster Display session 2
Resources:
Abstract
1025 - Liver metastases (LM) from intrahepatic cholangiocarcinoma (iCCA): Outcomes from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry and implications on current American Joint Committee on Cancer (AJCC) staging.
Presenter: Angela Lamarca
Session: Poster Display session 2
Resources:
Abstract
5813 - Is MGMT methylation a new therapeutic target for Biliary Tract Cancer?
Presenter: Monica Niger
Session: Poster Display session 2
Resources:
Abstract
5839 - Biliary Tract Cancers in Portuguese families with BRCA gene mutation: a retrospective study.
Presenter: Patricia Pereira
Session: Poster Display session 2
Resources:
Abstract
4338 - Selection of patients with hepatocellular carcinoma for selective internal radiation therapy based on tumour burden and liver function: a post-hoc analysis of the SARAH trial
Presenter: Daniel Palmer
Session: Poster Display session 2
Resources:
Abstract
1700 - Second-line chemotherapy (SLC) in Patients with Advanced Biliary tract and Gallbladder Cancers (ABGC) Prolongs Survival: A Retrospective Population-based Cohort Study
Presenter: Adnan Zaidi
Session: Poster Display session 2
Resources:
Abstract
5562 - Overall survival of patients with hepatocellular carcinoma receiving sorafenib versus selective internal radiation therapy with predicted dosimetry in the SARAH trial
Presenter: Neil Hawkins
Session: Poster Display session 2
Resources:
Abstract
1838 - Multicenter phase II trial of axitinib monotherapy for advanced biliary tract cancer refractory to gemcitabine-based chemotherapy
Presenter: Naohiro Okano
Session: Poster Display session 2
Resources:
Abstract
3641 - Soluble Programmed Death-ligand 1 indicate poor prognosis in hepatocellular carcinoma patients undergoing transcatheter arterial chemoembolization
Presenter: Xiaolu Ma
Session: Poster Display session 2
Resources:
Abstract
2733 - The Prognostic Nutritional Index (PNI) is an independent predictor of survival in advanced biliary cancers (ABC) receiving first-line chemotherapy (1L).
Presenter: Francesco Caputo
Session: Poster Display session 2
Resources:
Abstract