Abstract 5562
Background
Selective internal radiation therapy (SIRT) using yttrium-90 resin microspheres was compared to sorafenib 400mg bid in a phase 3 randomised trial (SARAH) in the treatment of intermediate or advanced hepatocellular carcinoma (HCC) not amenable to curative treatment. The trial did not show a survival benefit of SIRT over sorafenib in the intention to treat (ITT) population. The effectiveness of SIRT may depend on the tumour-absorbed dose, which can be predicted with the analysis of SPECT/CT imaging during each patient work-up, before the administration of SIRT. In this post hoc analysis we explored the comparative effectiveness of SIRT and sorafenib in a subgroup of patients defined by their predicted tumour-absorbed dose.
Methods
Cox proportional hazards regressions were conducted in the ITT population of the SARAH trial. Since predicted tumour-absorbed dose was only available for SIRT, the comparisons between SIRT at a given dose and sorafenib were not randomised. Inverse probability of treatment weighting (IPTW) using propensity scores was used to account for potential confounding by differences in prognostic factors between the treatment arms, with the sorafenib sample reweighted to match the SIRT patients. A cut-off value of 100 Gy was used for tumour absorbed dose, approximating the median dose, with 120 Gy used in a sensitivity analysis.
Results
For patients with a predicted dose ≥100 Gy, the hazard ratio (HR) for overall survival (OS) from the unweighted sample was 0.70 (95% CI: 0.50-0.98, p = 0.04). After reweighting, the HR was 0.74 (95% CI: 0.51-1.04, p = 0.09). Predicted mean OS was 22.5 months (mos) for SIRT vs 17.9 mos for sorafenib. Results were similar with a 120 Gy cut-off: the HR for OS was 0.76 (95% CI 0.52-1.10, p = 0.14). Among patients who received subsequent curative therapy post-SIRT, 11/12 were alive at the end of follow-up (median 26.6 mos, range 16.0-34.8) and only one had a predicted dose <100 Gy.
Conclusions
The analysis suggests that HCC patients may derive a meaningful benefit from treatment using SIRT with a predicted dose ≥100 Gy compared to sorafenib. This may inform personalised treatment selection and clinical trial design.
Clinical trial identification
NCT01482442.
Editorial acknowledgement
Legal entity responsible for the study
Sirtex Medical UK Ltd.
Funding
Sirtex Medical UK Ltd.
Disclosure
N.S. Hawkins: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Sirtex. P.J. Ross: Honoraria (self), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: Celgene; Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self): Roche; Honoraria (self), Travel / Accommodation / Expenses: Servier; Research grant / Funding (institution): Sanofi; Honoraria (self), Advisory / Consultancy: Shire; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sirtex. D.H. Palmer: Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca. V. Vilgrain: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sirtex. All other authors have declared no conflicts of interest.
Resources from the same session
2860 - Prognostic value of metabolic response assessed by 18FDG-PET after induction chemotherapy and after chemoradiotherapy (CRT) in localized esophageal squamous cell carcinoma (ESCC) patients (pts) receiving definite CRT (dCRT)
Presenter: Yeonghak Bang
Session: Poster Display session 2
Resources:
Abstract
3881 - Comprehensive genomic profiling of early-stage esophageal squamous cell carcinoma
Presenter: Jing Zuo
Session: Poster Display session 2
Resources:
Abstract
3944 - A novel nomogram and risk classification system predicting radiation pneumonitis in patients with esophageal cancer receiving radiotherapy
Presenter: Lu Wang
Session: Poster Display session 2
Resources:
Abstract
1956 - Drinking alcohol, smoking, multiple dysplastic lesions and the risk of field cancerization of squamous cell carcinoma in the esophagus and head and neck region
Presenter: Chikatoshi Katada
Session: Poster Display session 2
Resources:
Abstract
2144 - Neoadjuvant chemotherapy can eliminate the negative impact of postoperative infectious complications on recurrence in patients with esophageal cancer
Presenter: Kazuki Kano
Session: Poster Display session 2
Resources:
Abstract
2403 - Comparison of chemoradiotherapy (CRT) followed by consolidation with cisplatin and 5-fluorouracil (CF) versus definitive CRT with carboplatin and paclitaxel (CP) in esophageal cancer
Presenter: Marcelle Cesca
Session: Poster Display session 2
Resources:
Abstract
3247 - Paclitaxel in Combination with Cisplatin and 5-fluorouracil(TPF) Induction Chemotherapy for Locally Advanced Borderline-resectable Esophageal Squamous cell Carcinoma: A Phase II Clinical Trial
Presenter: Yuhong Li
Session: Poster Display session 2
Resources:
Abstract
4293 - Prognosis of esophageal squamous cell carcinoma based on local immunity evaluation
Presenter: Elena Zlatnik
Session: Poster Display session 2
Resources:
Abstract
5419 - Impact of Sarcopenia and adiposity in survival of metastatic esophageal cancer (MEC)
Presenter: Aline Fares
Session: Poster Display session 2
Resources:
Abstract
2083 - PALAESTRA - A phase II trial with short-course radiotherapy followed by chemotherapy as palliative treatment in esophageal adenocarcinoma
Presenter: David Borg
Session: Poster Display session 2
Resources:
Abstract