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SILIUS: Nexavar plus chemotherapy fails to improve overall survival in HCC
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BARCELONA — Nexavar plus a chemotherapy regimen was not superior to Nexavar alone in improving overall survival in a cohort of patients with hepatocellular carcinoma, according to findings presented at the International Liver Congress.
Masatoshi Kudo, MD, of Kinki University Hospital in Osaka-Sayama, Japan, and colleagues conducted a prospective, phase 3, randomized controlled trial comparing Nexavar (sorafenib, Bayer HealthCare) with sorafenib plus low-dose cisplatin/fluorouracil hepatic arterial infusion chemotherapy in a cohort of 206 patients with advanced HCC. The intention-to-treat population included 103 patients treated with 400 mg sorafenib twice a day and 103 patients treated with the same sorafenib dose plus cisplatin 20 mg/m2 on days 1 and 8 and 330 mg/m2 5- fluorouracil continuously on days 1 through 5 and 8 through 12.
Overall survival served as the primary outcome measure. Time to progression, progression free survival, overall response rate, disease control rate and safety also underwent analysis.
The final analysis included 102 patients in the sorafenib-only arm and 88 patients in the sorafenib plus chemotherapy arm. “The characteristics of study patients were well balanced in terms of age, gender, stage, [Eastern Cooperative Oncology Group] performance status and cirrhotic status of Child-Pugh score,” Kudo said.
Primary endpoint results indicated a median OS of 11.8 months for both treatment groups (HR = 1; 95% CI, 0.7-1.4). “The primary endpoint of improvement in overall survival was not met in this trial,” Kudo said.
The researchers also conducted a subgroup analysis based on portal invasion. Among patients with mild portal invasion, median OS was 14.4 months (95% CI, 9.3-19.5 months) in the sorafenib group and 12.6 months (95% CI, 4.3-20.9 months) in the chemotherapy group (HR = 1.4; 95% CI, 0.83-2.26). For patients with main portal vein invasion, the median OS was 6.5 months (95% CI, 4.5-8.4 months) in the sorafenib group and 11.4 months (95% CI, 7.9-15.9 months) in the chemotherapy group (HR = 0.49; 95% CI, 0.24-1.8).
Secondary endpoint results indicated an overall response rate of 17.5% in the sorafenib group and 36.3% in the chemotherapy group (P = .002). The disease control rate was 72.6% in the sorafenib arm and 64.7% in the chemotherapy arm (P = .21).
In another analysis, the researchers assessed tumor response and OS. Patients in the sorafenib arm who achieved complete response or partial response survived for a median of 27.2 months (95% CI, 15.7-38.8 months), whereas those who reached stable disease or disease progression survived for a median of 8.9 months (95% CI, 6.4-11.4 months). In the chemotherapy arm, patients with a complete or partial response survived for a median of 23.0 months (95% CI, 13.8-32.2 months), whereas those with stable disease or disease progression survived for 9.9 months (95% CI, 8.3-115 months).
Anemia, decreased neutrophil and platelet counts, obstruction of artery, thrombosis or vasculitis and implanted catheter system trouble were the most frequently reported adverse events.
“Sorafenib with low-dose [cisplatin and 5-FU] hepatic arterial infusion chemotherapy did not improve OS in unresectable HCC patients compared with sorafenib,” Kudo said. “However, time to progression, progression-free survival and overall response rate in combination therapy were significantly better than those in sorafenib.”
Kudo noted that OS was significantly better in patients who responded to either sorafenib or combination therapy than in non-responders. The higher overall response rate associated with combination therapy compared with sorafenib-only resulted in “a much higher fraction of the enrichable patient population who had survival benefit from the combination therapy compared with sorafenib alone,” he said. Kudo added that in patients with main portal vein invasion, combination therapy improved 1- and 2-year survival rates.
Reference:
Kudo M, et al. Abstract LB04. Presented at: International Liver Congress; April 13-17, 2016; Barcelona.
Disclosures: Kudo reports receiving grants from Astellas, Chugai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, MSD, Otsuka, Sumitomo Dainippon, Takeda, Taiho, Tsumura, Yakult and Zeria; and giving sponsored lectures for Bayer, Eisai, Kowa, Kyowa Hakko Kirin, MSD, Sumitomo Dainippon and Taiho.