by ecancer reporter Janet Fricker

Advanced or inoperable Hepatocellular Carcinoma (HCC) patients randomised to liver-directed Selective Internal Radiation Therapy (SIRT) show similar overall survival (OS) to patients randomised to the standard of care sorafenib, found the SARAH study presented at The International Liver Congress™, Amsterdam, The Netherlands, 19-23 April, 2017.

The investigator-led phase III trial showed patients receiving SIRT had statistically letreatment-relatedted adverse effects and better quality of life.

“In terms of what matters for patients the findings from this first large head-to-head comparison of liver directed SIRT and systemic chemotherapy with sorafenib also show clearly that liver-directed procedures with SIR-spheres result in a significantly better tolerance of treatment and quality of life,” said principal investigator Professor Valérie Vilgrain, from Hôpital Beaujon Service de Radiologie, Paris.
“I believe this consideration should be a critical factor in selecting first-line treatment for this patient population in the future.”

SIRT, is a form of internal radiation therapy involving Y-90 resin microspheres (diameter between 20-60 microns), delivered via catheter to the hepatic artery.

The beta radiation emitting microspheres lodge preferentially in microvasculature surrounding tumours, minimizing systemic effects.

In the randomized, controlled, open-labelled SARAH (SorAfenib versus Radioembolization in Advanced Hepatocellular carcinoma) study, between December 2011 and February 2015, 459 patients with locally advanced HCC and patients not resectable who had failed transarterial chemoembolization (TACE) were randomised 1:1 to SIRT (n=237) or sorafenib (n=222,  800 mg daily).

The per protocol population (treatment with no major deviations) was SIRT (n=174) and sorafenib (n=206).

Almost 70% of the patients in the SARAH study had advanced HCC (Barcelona Clinic Liver Cancer stage C), with portal vein thrombosis and no spread beyond the liver.

Most of the remaining patients had failed two cycles of TACE.

SARAH was conducted in 25 centres across France.

Results for the intention-to-treat (ITT) population show median OS was 8.0 months for SIRT versus 9.9 months for sorafenib (p=0.18); while for those actually receiving treatment OS was 9.9 months for SIRT versus  9.9 months for sorafenib (p=0.92).

The study furthermore showed significantly fewer patients in the SIRT arm had any treatment related side effects (76.5% for SIRT versus 94.0% for sorafenib; p<0.001), and that they were less severe (≥ grade 3, 40.7% for SIRT versus 63.0% for sorafenib, p<0.001).

General treatment-related symptoms such as fatigue (42% versus 65%; p<0.001), abdominal pain (20% versus 29%; p=0.032), nausea or vomiting (12% versus 23%, p=0.001) and infection (4% versus 11%, p=0.007) were less for SIRT.

Additionally, fewer SIRT patients experienced treatment-related diarrhoea (13% versus 68% for sorafenib; p<0.001), hand-foot skin reaction (0.4% versus 21%; p<0.001), weight loss (6% versus 21%; p<0.001), alopecia (0% vs 16%; p<0.001), and infections (94% versus 11%; p=0.007).

Quality of life (EORTC QLQ-C30 questionnaire) showed patients receiving SIRT reported significantly better quality of life (P=0.005), and were more likely to maintain health status over time (p=0.045).

Objective response (complete response and partial response, measured with RECIST v 1.1) was 19.0% for patients treated with SIRT versus 11.6% for patients treated with sorafenib (p=0.042).

Although numbers were small, Professor Vilgrain reported, more SIRT patients were able to access curative treatments.

One explanation for SIRT patients failing to receive per protocol treatment, explained Professor Vilgrain, was that sorafenib patients started treatment immediately after randomisation while SIRT patients often waited up to three weeks, raising the possibility their condition could progress.

Further analysis, said Professor Vilgrain, will evaluate prognostic factors for SIRT, cost effectiveness and dose related efficacy.

The results of SIRveNIB, a parallel study to SARAH in more than 360 Asia Pacific HCC patients have been accepted for the ASCO meeting in Chicago in June.

Source: International Liver Congress

Reference: GS-012. Vilgrain V, Bouattour M, Sibert A, et al. SARAH: a randomized controlled trial comparing efficacy and safety of selective internal radiation therapy (with ytrrium-90 microspheres) and sorafenib in patients with locally advanced hepatocellular carcinoma.