SIRT not superior to sorafenib in improving OS in locally advanced HCC, SIRveNIB study shows
Selective internal radiation therapy (SIRT) did not fare better than sorafenib in terms of overall survival (OS) in patients with locally advanced hepatocellular carcinoma (HCC), though it appeared to be associated with fewer total adverse events, according to findings of the phase III, multicentre (11 Asia-Pacific countries), open-label SIRveNIB* study.
“In this study, SIRT was not shown to be superior to sorafenib with respect to [OS],” said Professor Pierce Chow from the National Cancer Centre Singapore who presented the findings at the annual meeting of the American Society of Clinical Oncology (ASCO 2017) held in Chicago, Illinois, US.
“However, patients treated with SIRT had a significantly better tumour-response rate [and] significantly fewer ... adverse events and severe adverse events when compared with those treated with sorafenib,” he said.
In this study, 360 patients aged ≥18 years with locally advanced HCC but no extrahepatic metastasis and ECOG status 0–1 and having undergone ≤2 prior hepatic arterial therapies were randomized to receive a single injection of SIRT with Y90 resin microspheres (n=182) or sorafenib (400 mg BD orally, n=178) until disease progression or unacceptable toxicity. The final treated population comprised 130 and 162 patients in the SIRT and sorafenib arms, respectively.
In the intent-to-treat population, median OS was 8.84 and 10.02 months in the SIRT and sorafenib arms, respectively (hazard ratio [HR], 1.12, 95 percent confidence interval [CI], 0.88–1.42; p=0.360). Median OS was also comparable between the SIRT and sorafenib arms in the treated population (11.27 vs 10.41 months, HR, 0.86, 95 percent CI, 0.56–1.13; p=0.273). [ASCO 2017, abstract 4002]
SIRT appeared to fare better than sorafenib in terms of tumour-response rate in both the intent-to-treat population (16.5 percent vs 1.7 percent; p<0.001) and treated population (23.1 percent vs 1.9 percent; p<0.001).
There was no significant difference in disease-control rate between SIRT and sorafenib in the intent-to-treat population (41.8 percent vs 42.7 percent; p=0.915) and treated population (58.5 percent vs 46.9 percent; p=0.059). Time to progression was also comparable between SIRT and sorafenib in the intent-to-treat population (HR, 0.88, 95 percent CI, 0.69–1.11; p=0.287) and favoured the SIRT arm in the treated population (HR, 0.73, 95 percent CI, 0.56–0.95; p=0.019).
In the treated population, patients on SIRT had better progression-free survival (median 6.28 vs 5.22 months, HR, 0.73, 95 percent CI, 0.56–0.93; p=0.013) and progression-free survival in the liver (median 6.67 vs 5.22 months, HR, 0.71, 95 percent CI, 0.55–0.92; p=0.009)
SIRT was associated with a better side effect profile with fewer patients on SIRT experiencing at least one treatment-related adverse event (AE; 31.5 percent vs 74.7 percent; p<0.0001), at least one grade ≥3 treatment-related AE (13.1 percent vs 37.7 percent; p<0.0001), and at least one serious AE (20.8 percent vs 35.2 percent; p=0.0091) compared with those on sorafenib.
According to discussant Associate Professor Katie Kelley from the University of California, San Francisco, California, US, the high dropout rate between the intention-to-treat and treated population (28.6 percent vs 9 percent among patients on SIRT vs sorafenib) should be taken into consideration.
“This is a negative study. Further, there are several potential confounding factors which may have favoured SIRT, including the imbalance in post-randomization dropout [which may enrich for better prognosis in the SIRT-treated arm] and possible receipt or unknown receipt of downstream therapies,” she said.
Kelley also highlighted that SIRveNIB was “not designed to test for non-inferiority vs sorafenib” and thus, “established important benchmarks for safety and activity of SIRT with Y90 resin microspheres in a Barcelona Clinic Liver Cancer B predominant population”.
“In the changing landscape of HCC ahead, SIRT warrants further study in sequence or combination with new therapies including immune-oncology agents,” said Kelley.