Continuous Sunitinib treatment in patients with advanced hepatocellular carcinoma: a Swiss Group for Clinical Cancer Research (SAKK) and Swiss Association for the Study of the Liver (SASL) multicenter phase II trial (SAKK 77/06)

Abstract

Background: Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients with hepatocellular carcinoma (HCC).

Patients and methods: Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease, and Child-Pugh class A or mild Child-Pugh class B liver dysfunction. Patients received 37.5 mg SU daily until progression or unacceptable toxicity. The primary endpoint was progression-free survival at 12 weeks (PFS12).

Results: Forty-five patients were enrolled. The median age was 63 years; 89% had Child-Pugh class A disease and 47% had distant metastases. PFS12 was rated successful in 15 patients (33%; 95% confidence interval, 20%-47%). Over the whole trial period, one complete response and a 40% rate of stable disease as the best response were achieved. The median PFS duration, disease stabilization duration, time to progression, and overall survival time were 1.5, 2.9, 1.5, and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent. None of the 33 deaths were considered drug related.

Conclusion: Continuous SU treatment with 37.5 mg daily is feasible and has moderate activity in patients with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design (>13 PFS12 successes), the therapy is considered promising. This is the first trial describing the clinical effects of continuous dosing of SU in HCC patients on a schedule that is used in an ongoing, randomized, phase III trial in comparison with the current treatment standard, sorafenib (ClinicalTrials.gov identifier, NCT00699374).

Conflict of interest statement

Disclosures: Dieter Koeberle: Consultant/advisory role: Bayer; Michael Montemurro: Honoraria: Novartis; Panagiotis Samaras: None; Pietro Majno: None; Mathew Simcock: None; Andreas Limacher: None; Stefanie Lerch: None; Katalin Kovàcs: None; Roman Inauen: None; Vivianne Hess: None; Piercarlo Saletti: None; Markus Borner: None; Arnaud Roth: Consultant/advisory role: Pfizer Oncology; György Bodoky: None.

The paper discusses sunitinib (Pfizer, Inc.) as an investigational unlabeled product for hepatocellular carcinoma.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

Figures

Figure 1.

Waterfall plot of the maximum percentage change in the sum of the largest diameter of target lesions.

Figure 2.

Kaplan–Meier estimates of progression-free survival (PFS) and overall survival (OS).

Figure 3.

Kaplan–Meier estimates of overall survival stratified by baseline vitamin B12 level.