In a retrospective study reported in the Journal of Clinical Oncology, Reiss et al found that reducing the starting dose of sorafenib (Nexavar) was associated with noninferior overall survival, reduced cost, and lower risk of discontinuing treatment in patients with advanced hepatocellular carcinoma.
The study involved data from 4,903 patients from 128 Veterans Health Administration hospitals who were prescribed sorafenib for hepatocellular carcinoma between January 2006 and April 2015. Propensity-score matching (1:1) was used to account for potential treatment bias. Hazard ratios (HRs) were calculated using Cox regression and were tested against a noninferiority margin of HR = 1.1. The primary endpoint was overall survival of patients prescribed the standard starting sorafenib dose of 800 mg/d vs those prescribed a lower starting dose (< 800 mg/d).
Survival and Other Outcomes
Overall, 3,094 patients (63%) received the standard starting dose, and 1,809 (37%) received a reduced starting dose (average starting dose = 367 mg/day). Those receiving a reduced dose were more likely to have Barcelona Clinic Liver Cancer stage D disease (P < .001), higher Model for End-Stage Liver Disease Sodium scores (P < .001), higher Child-Turcotte-Pugh scores (P < .001), and higher Cirrhosis Comorbidity Index scores (P = .01). Without adjustment, the reduced-dose group had poorer median overall survival (median = 200 vs 233 days, HR = 1.10, P = .002). After propensity-score matching and multivariate analysis, no significant difference in overall survival was observed (adjusted HR = 0.92, 95% confidence interval = 0.83–1.01), with the hazard ratio being significantly below the noninferiority margin (P < .001).
Patients receiving reduced starting doses had significantly lower cumulative sorafenib cost (median = $5,636 vs $8,661, P < .001). After propensity matching, there was a trend toward a reduced likelihood of discontinuing sorafenib due to adverse events in the reduced-dose group (19.6% vs 22.4%, P = .056), including a reduced likelihood of discontinuing treatment due to gastrointestinal adverse events (8.7% vs 10.8%, P = .047).
The investigators concluded: “The initiation of sorafenib therapy at reduced dosages was associated with reduced pill burden, reduced treatment costs, and a trend toward a decreased rate of discontinuing sorafenib because of adverse events. Reduced dosing was not associated with inferior [overall survival] relative to standard dosing.”
The study was supported by Bayer HealthCare Pharmaceuticals, the VA HIV, Hepatitis and Related Conditions Programs in the Office of Specialty Care Services, and a grant from the National Cancer Institute.
Kim A. Reiss, MD, of the University of Pennsylvania Perelman School of Medicine, is the corresponding author of the Journal of Clinical Oncology article.
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