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Reduced Nexavar dosage yields cost benefits, does not affect OS in HCC

Patients with hepatocellular carcinoma who started Nexavar therapy at reduced dosages had a lower total cumulative pill cost and were less likely to discontinue due to adverse effects, according to recently published data. Additionally, lower starting doses did not affect overall survival.

“Prior small retrospective studies have suggested that using a [Nexavar] dosage escalation strategy might be beneficial, or at least not harmful, to patients with HCC,” Kim A. Reiss, MD, from the Perelman Center for Advanced Medicine, Philadelphia, and colleagues wrote. “This retrospective analysis of nearly 5,000 patients with HCC who were prescribed [Nexavar] suggests that starting patients on a reduced starting dose does not reduce OS after propensity score matching for multiple clinical variables.”

The cohort included 4,903 patients with HCC from the Veterans Health Administration, of whom 3,094 received a standard Nexavar (sorafenib, Bayer) dosage of 800 mg per day. The remaining 1,809 patients received a reduced starting dosage.

Patients in the reduced dosage group were more likely to have Barcelona clinic liver cancer stage D (P < .001), had higher MELD-Na scores (P < .001), higher electronic Child-Turcotte-Pugh scores (P < .001), higher CirCom scores (P = .01), more frequent active alcohol abuse (P = .003), increased severity of ascites (P < .001), and more frequent hepatic encephalopathy (P < .001).

The average reduced starting dosage of sorafenib was 367 mg per day. By the end of the first month of treatment, the average dosage was 791 mg per day for those who started with the standard treatment and 412 mg per day for those who started with a reduced dosage. At 6 months, the average dosage remained lower in the reduced dosage group compared with the standard dosage group (573 vs. 678 mg/d; P < .001).

While both groups received a similar number of days of sorafenib therapy, patients in the reduced dosage group received fewer pills than the standard group (median, 180 vs. 276; P < .001). The total pill-related costs were significantly lower for the reduced dosage group compared with the standard dosage group (median, $5,636 vs. $8,661; P < .001).

The researchers matched 1,675 patients from the standard sorafenib dosage group 1:1 with patients from the reduced dosage group. Patients who received reduced dosages were less likely to discontinue sorafenib therapy due to gastrointestinal adverse events (8.7% vs.10.8%; P = .047).

In a subgroup analysis, the researchers found no significant difference in overall survival rates between the two groups. However, patients with Eastern Cooperative Oncology Group performance status 3 to 4 (HR = 1.07; 95% CI, 0.33-3.53), Child-Turcotte-Pugh class C (HR = 1.02; 95% CI, 0.55-1.88) and Barcelona clinic liver cancer stage C (HR = 0.96; 95% CI, 0.79-1.17) or stage D (HR = 0.88; 95% CI, 0.53-1.47) had inferior outcomes compared with the rest of the cohort.

“The observed practice patterns suggest that this strategy is becoming more common, although most physicians still start at full dosage therapy,” the researchers concluded. “Our data suggest that the initiation of sorafenib at a reduced dosage may be a safe and reasonable strategy for some patients with HCC.” – by Talitha Bennett

Disclosure: Healio.com/Hepatology was unable to determine relevant financial disclosures at the time of publication.