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
5747 - The routine use of sentinel lymph node biopsy in high risk DCIS lesions is not justified
Presenter: Fanny Preat
Session: Poster Display session 2
Resources:
Abstract
1837 - Oncological impact of re-excision for positive margin status after breast conserving surgery in invasive breast cancer
Presenter: Kenjiro Jimbo
Session: Poster Display session 2
Resources:
Abstract
4347 - Pneumonitis and fibrosis after breast cancer radiation.
Presenter: Jarle Karlsen
Session: Poster Display session 2
Resources:
Abstract
2280 - Prognosis of mastectomy with reconstruction after neoadjuvant chemotherapy: a nationwide study in Korean Breast Cancer Society
Presenter: Sungmin Park
Session: Poster Display session 2
Resources:
Abstract
804 - A negative prognosis of radiotherapy-induced lower lymphocyte to monocyte ratio in patients with breast cancer
Presenter: Chang-ik Yoon
Session: Poster Display session 2
Resources:
Abstract
2701 - Patient data to monitor clinical patterns in early and advanced breast cancer in Europe
Presenter: Francesco Giusti
Session: Poster Display session 2
Resources:
Abstract
1437 - A critical appraisal of quality indicators of breast cancer treatment in Belgium
Presenter: Didier Verhoeven
Session: Poster Display session 2
Resources:
Abstract
1534 - Predictors of adherence among post-menopausal women receiving adjuvant endocrine therapy for breast cancer in Ontario, Canada
Presenter: Phillip Blanchette
Session: Poster Display session 2
Resources:
Abstract
4363 - Evaluation of endocrine therapy and patients preferences in early breast cancer: results of Elena study
Presenter: Emilia Montagna
Session: Poster Display session 2
Resources:
Abstract
2679 - Baseline Quality of life (QoL) and chemotherapy related toxicities (CRT) in localized breast cancer (BC) patients (pts): the French multicentric prospective CANTO cohort study
Presenter: Idlir Licaj
Session: Poster Display session 2
Resources:
Abstract