Results Presented From Asian and European Studies of Sirtex Microspheres
June 5, 2017—Sirtex Medical Limited announced that a head-to-head study has shown that selective internal radiation therapy (SIRT) with the company's Sir-Spheres yttrium-90 (Y-90) resin microspheres, administered once directly to the liver, offers important benefits compared with twice-daily oral doses of sorafenib, the current standard of care for advanced hepatocellular carcinoma (HCC). Results of the 360-patient SIRveNIB study were presented by principal investigator Prof. Pierce Chow, MD, at ASCO 2017, the annual meeting of the American Society of Clinical Oncology held June 2–6 in Chicago, Illinois.
In the company's announcement, Prof. Chow commented, "We found that the Asian patients with locally advanced HCC who were treated with Y-90 resin microspheres had a significantly better tumor response rate of 16.5% compared with 1.7% for sorafenib (P < .001) in the intent-to-treat analysis, and 23.1% for SIRT compared with 1.9% (P < .001) in the treated population, which represents the patients who actually received their allocated treatment. They also experienced almost a two-fold decrease in severe adverse events (grade ≥ 3; 27.7% vs 50.6%; P < .0001) compared with those treated with sorafenib."
Prof. Chow, who is Senior Consultant Surgeon at the National Cancer Center Singapore and the Singapore General Hospital, continued, "The primary endpoint of the study, overall survival, was not met. If you look at patients assigned to each therapy in the intent-to-treat analysis, median survival in the Y-90 resin microspheres study arm was 8.84 versus 10.02 months for the sorafenib group (P = .36). This difference is not statistically significant. However, this analysis does not take into account that more than a quarter of the patients (28.6%; 52 patients) who were scheduled to receive Y-90 therapy actually didn't receive treatment. If you look at the survival data based solely on those patients who actually received Y-90 resin microspheres, median overall survival was 11.3 months compared with 10.4 months for those treated with sorafenib, an opposite trend that is also not statistically significant."
Prof. Chow added, "The comparative data on side effects reported in the SIRveNIB study unequivocally favored Y-90 resin microspheres over sorafenib. In addition to two-fold fewer severe adverse events, we observed about one-fourth as many adverse events (60% vs 84.6%; P< .0001) as well as fewer serious adverse events (20.8% vs 35.2%; P = .009). Specifically, patients treated with Y-90 resin microspheres reported substantially less fatigue (3.8% vs 15.4%), diarrhea (1.5% vs 29.6%), hand-foot skin reaction (0.8% vs 54.9%), alopecia (0% vs 9.9%), as well as hypertension (0% vs 14.8%), than those treated with sorafenib."
The company reported that side effects specifically associated with Y-90 resin microspheres were infrequent and manageable. The incidence rate of gastric ulcer was 0.8%, upper gastrointestinal hemorrhage was 1.5% (vs 1.9% for sorafenib), jaundice was 1.5% (vs 1.9%), and portal hypertension was 0% in the SIRT arm (vs 0.6%), which were not significantly different from the sorafenib group. The incidence rate of radiation hepatitis (1.5%) was consistent with previously published studies.
As noted in the company's announcement, although these differences were not significant in the intent-to-treat population, patients who actually received Y-90 resin microspheres in the SIRveNIB study experienced additional treatment benefits in respect to other secondary endpoints, including overall progression-free survival (6.3 vs 5.2 months; hazard ratio [HR] = 0.73; P = .013), progression-free survival in the liver (6.7 vs. 5.2 months; HR = 0.71; P = .09), overall time to progression (6.4 vs 5.4 months; HR = 0.73; P = .019), and time to progression in the liver (6.8 vs 5.5 months; HR = 0.72; P = .013).
Sirtex noted that the SIRveNIB results reported at ASCO essentially mirrored the findings of the 459-patient European SARAH study that were presented by Prof. Valerie Vilgrain, MD, at the 2017 International Liver Congress on April 23 in Amsterdam, The Netherlands. Prof. Vilgrain is Chief of Radiology at Hôpital Beaujon in Clichy, France.
As summarized by the company, Prof. Vilgrain reported that the tumor response rate in SARAH was 19% for SIRT versus 11.6% for sorafenib (P = .042). In SIRveNIB, tumor response rate was 16.5% vs 1.7%; P < .001. Safety profiles were also similar. In SARAH, significantly fewer patients (76.5% vs 94%; P < .001) treated with Sir-Spheres had any treatment-related side effects; and these were also less severe (grade ≥ 3; 40.7% vs 63%; P < .001). In SIRveNIB, fewer patients (60% vs 84.6%; P < .0001) treated with Sir-Spheres had any side effects, severe side effects (grade ≥ 3; 27.7% vs 50.6%; P < .0001), or serious adverse events (20.8% vs 35.2%; P = .009).
In SARAH, patients in the Sir-Spheres arm also maintained a significantly better quality of life over time by Global Health Status using the EORTC QLQ-C30 questionnaire compared to those on sorafenib, who experienced a significant and sustained decline in quality of life compared to baseline (group effect, P = .005; time effect, P < .001; between-group difference over time, P = .045). Survival differences in neither study were significant, whether by intent-to-treat or per-protocol analysis, reported Sirtex.