Effect of sorafenib starting dose and dose intensity on survival in patients with hepatocellular carcinoma: Results from a Canadian Multicenter Database

Abstract

Background Sorafenib has been shown to improve survival in patients with advanced hepatocellular carcinoma (HCC), however, full dose can be difficult to tolerate. The aim of this study was to determine whether sorafenib starting dose and mean dose intensity affect survival. Methods Patients treated with sorafenib for HCC from January 2008 to July 2016 in several Canadian provinces were included and retrospectively analyzed. The primary end point was overall survival (OS) of patients starting on sorafenib full dose compared to reduced dose. Secondary analysis compared OS with different mean dose‐intensity groups. Survival outcomes were assessed with Kaplan‐Meier curves and Cox proportional hazards models. A propensity score analysis was performed to account for treatment bias and confounding. Results Of 681 patients included, sorafenib was started at full dose in 289 patients (42%). Median survival for starting full and reduced dose was 9.4 months and 8.9 months ( P = .15) respectively. After propensity score matching and adjusting for potential confounders there was still no difference in survival (HR 0.8, 95% CI, 0.61‐1.06, P = .12). Almost half of the patients (45%) received a dose intensity < 50%. Median survival for mean dose intensity > 75%, 50%‐75%, and < 50% were 9.5 months, 12.9 months, and 7.1 months ( P = .005) respectively. In multivariable models, starting dose(HR 1.16, 95% CI 0.93‐1.44, P = .180) and mean dose intensity were not associated with survival. Conclusions Starting HCC patients on a reduced dose of sorafenib compared to full dose may not compromise survival. Mean dose‐intensity of sorafenib may also not affect survival.

Real-World Data for Lenvatinib in Hepatocellular Carcinoma (ELEVATOR): A Retrospective Multicenter Study

“…However, in clinical practice, a considerable proportion of patients with advanced HCC does not fulfill the inclusion criteria of a clinical trial, and in the real-world setting, it is not uncommon that lenvatinib treatment is initiated at a lower than recommended dose. Similar to the observations published for sorafenib, our data suggest that a reduced lenvatinib dosage may be a safe and a reasonable strategy for some patients with HCC [29].…”

Multicenter retrospective study of initial treatment outcome and feasibility of initiating dose reduction of cabozantinib in unresectable hepatocellular carcinoma

“…[15][16][17] Moreover, some studies on dose reduction initiation in multitargeted therapy for HCC have been reported for SOR treatment, with no difference in outcome and better safety in dose reduction initiation cases. [18][19][20] Optimizing the dosage according to the therapeutic situation is critical to maximize the effect of CAB treatment, and is considered beneficial as this study suggests the efficacy and safety of using a reduced dosage.…”

Real-world treatment patterns, clinical outcomes, and health care resource utilization in advanced unresectable hepatocellular carcinoma

“…A more recent study found that small dose reductions in sorafenib were associated with longer adherence, higher cumulative dosage, and better overall survival compared with patients who maintained the standard dosage (21). Similar work was also shown by the HCC Cancer Health Outcomes Research Database (CHORD) consortium in Canada, who showed that neither starting dose (full 800mg/day versus reduced <800mg/ day) dose of sorafenib nor dose intensity compromise survival (22). Taken together, these results have important implications for the administration of first-line therapy for advanced HCC patients.…”