A phase III trial has found that selective internal radiation therapy may be safer for patients with advanced HCC than sorafenib.
The French investigator-led SorAfenib versus Radioembolization in Advanced Hepatocellular Carcinoma (SARAH) trial - the first ever hepatocellular carcinoma (HCC) study of a liver-directed therapy against systemic chemotherapy - was recently presented at the International Liver Congress 2017, held in Amsterdam, the Netherlands.
"For patients with advanced HCC or those failing transcatheter chemoembolization (TACE), we have for the past 10 years relied upon oral systemic treatment with sorafenib, which was shown to extend survival compared to placebo," explained principal investigator Prof. Valérie Vilgrain, from Hôpital Beaujon Service de Radiologie in Paris, France. "But it also causes many side effects that can compromise patients' quality of life."
Selective internal radiation therapy (SIRT) is a form of internal radiation therapy involving Y-90 resin microspheres, with median diameters of 32.5 microns, delivered directly to inoperable liver tumors via the hepatic artery.
The resin microspheres, which emit beta radiation penetrating an average of 2.5 millimeters in tissue, lodge preferentially in microvasculature surrounding tumors, thereby minimizing normal liver effect. SIRT involves one to two treatments, while the multikinase inhibitor sorafenib - currently the only approved systemic treatment for advanced liver cancer - involves taking tablets twice daily.
SIRT led to fewer side effects than sorafenib
In the open-label phase III SARAH study, between December 2011 and February 2015, 459 patients with locally advanced HCC and patients not resectable who had failed TACE were randomized 1:1 to SIRT (n=237) or sorafenib (n=222, 800 milligrams daily).
The per protocol population receiving treatment with no major deviations were SIR spheres (n=174) and sorafenib (n=206). Patients were treated in 25 clinical centers located across France.
Results show that for the intention-to-treat population, median overall survival (OS) - which was the primary endpoint - was 8 months in the SIRT arm versus 9.9 months in the sorafenib arm (p=0.18), while for those who actually received treatment, OS was 9.9 months in the SIRT arm versus 9.9 months in the sorafenib arm (p=0.92).
The objective response (complete response and partial response, measured with RECIST 1.1) was 19 percent for patients treated with SIRT versus 11.6 percent for patients treated with sorafenib (p=0.042). Although numbers were small, Prof. Vilgrain reported that more patients in the SIRT arm were able to access curative treatments.
Furthermore, the study showed that significantly fewer patients treated with SIRT had any treatment-related side effects (76.5 percent for SIRT versus 94 percent for sorafenib; p<0.001), and for those that did experience side effects, they were less severe (≥ grade 3, 40.7 percent for SIRT versus 63 percent for sorafenib, p<0.001).
General treatment-related symptoms, such as fatigue (42 percent versus 65 percent; p<0.001), abdominal pain (20 percent versus 29 percent; p=0.032), nausea or vomiting (12 percent versus 23 percent, p=0.001), and infection (4 percent versus 11 percent, p=0.007), were also considerably less frequently reported for patients receiving SIRT.
Additionally, fewer patients receiving SIRT experienced treatment-related diarrhea (13 percent versus 68 percent for sorafenib; p<0.001), hand-foot skin reaction (0.4 percent versus 21 percent; p<0.001), anorexia (13 percent versus 32 percent; p<0.001), weight loss (6 percent versus 21 percent; p<0.001), alopecia (0 percent versus 16 percent; p<0.001), infections (94 percent versus 11 percent; p=0.007), hypertension (3 percent versus 13 percent; p<0.001), and non-gastrointestinal hemorrhage (3 percent versus 10 percent; p=0.002).
Better quality of life with SIRT
Quality of life was measured every 3 months using the EORTC QLQ-C30 questionnaire - the results of which showed that 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) than those taking sorafenib.
One explanation for the higher numbers of SIRT patients not receiving the per protocol treatment, explained Prof. Vilgrain, was that sorafenib patients started treatment a day after randomization, while SIRT patients waited up to 3 weeks, with the possibility that their condition could progress.
"SIRT offers a better tolerance with less treatment-related adverse events and a better quality of life over time than sorafenib. And we think this is very important when patients suffer from a severe disease with a poor life expectancy," said Prof. Vilgrain, adding that the results opened a new door in the field of HCC.
Further analysis, she said, will evaluate prognostic factors, cost effectiveness, and the dose-related efficacy for SIRT.
The results of SIRveNIB, a parallel study to SARAH in more than 360 Asia Pacific HCC patients, will be presented at the ASCO meeting in Chicago in June.