Field-practice study of sorafenib therapy for hepatocellular carcinoma: A prospective multicenter study in Italy

Abstract

on behalf of the SOFIA (SOraFenib Italian Assessment) study group A multicenter randomized controlled trial established sorafenib as a standard of care for patients with advanced hepatocellular carcinoma (HCC). Because the study was prematurely interrupted due to survival benefits in the sorafenib arm, we conducted an observational study to adequately assess risks and benefits of this regimen in field practice. Starting in 2008, all clinically compensated patients with advanced HCC and those with an intermediate HCC who were unfit or failed to respond to ablative therapies were consecutively evaluated in six liver centers in Italy, for tolerability as well as radiologic and survival response to 800-mg/d sorafenib therapy. Treatment was down-dosed or interrupted according to drug label. Two hundred ninety-six patients (88% Child-Pugh A, 75% Barcelona Clinic Liver Cancer [BCLC]-C, and 25% BCLC-B) received sorafenib for 3.8 months (95% CI 3.3-4.4). Two hundred sixty-nine (91%) patients experienced at least one adverse event (AE), whereas 161 (54%) had to reduce dosing. Treatment was interrupted in 103 (44%) for disease progression, in 95 (40%) for an AE, and in 38 (16%) for liver deterioration. The median survival was 10.5 months in the overall cohort, 8.4 months in BCLC-C versus 20.6 months in BCLC-B patients (P < 0.0001), and 21.6 months in the 77 patients treated for >70% of the time with a half dose versus 9.6 months in the 219 patients treated for >70% of the time with a full dose. At month 2 of treatment, the overall radiologic response was 8%. Eastern Cooperative Oncology Group performance status, macrovascular invasion, extrahepatic spread of the tumor, radiologic response at month 2, and sorafenib dosing were independent predictors of shortened survival. Conclusion: Overall, safety, effectiveness, and generalizability of sorafenib therapy in HCC was validated in field practice. The effectiveness of half-dosed sorafenib may have implications for tailored therapy.

Human and Mouse VEGFA-Amplified Hepatocellular Carcinomas Are Highly Sensitive to Sorafenib Treatment

“…The response to sorafenib seems to be variable, and treatment is associated with signifi cant side effects (3)(4)(5)(6)(7)(8). Importantly, there are no clinically applied biomarkers for predicting sorafenib response in HCC ( 10 ).…”

“…Sorafenib is the mainstay of therapy for advanced HCC and the only systemic drug that has shown any survival advantage in HCC so far ( 3,4 ). However, patients' response is modest, and sorafenib treatment is associated with side effects (3)(4)(5)(6)(7)(8). Thus, several studies looked for predictive markers for sorafenib response (9)(10)(11), yet no such biomarkers have entered the clinical setting.…”

Refining Sorafenib Therapy: Lessons from Clinical Practice

“…Since approval was granted to sorafenib, physicians have accrued a wealth of experience with the fine-tuning of sorafenib in their daily clinical practice, and several 'real-world' studies have continued to investigate the safety and efficacy of sorafenib. Among them is a multinational postmarketing study, GIDEON, and the Italian field-practice study by the Sorafenib Italian Assessment (SOFIA) study group [7][8][9][10][11], as well as a number of other studies in Europe and North America [12][13][14][15] . These real-world experiences have allowed us to assess sorafenib in patients who are not selected by strict clinical trial criteria but by physician judgment, including patients with comorbidities and those receiving concomitant medication.…”

“…It is also recommended for patients with intermediate HCC who are unsuitable for treatment with TACE or have TACE-refractory disease [4,24] To our knowledge, no clinical trial in HCC has prospectively compared a different starting dose of sorafenib with the approved dose of 800 mg/day. The SOFIA study reported outcomes for patients who maintained an initial dose of 800 mg/day and for patients in whom the initial dose was reduced in order to manage AEs [9]. In a retrospective analysis, the authors reported a median overall survival (OS) of 21.6 months for patients who received 400 mg/day of sorafenib for 70% of the treatment period and 9.6 months for those who maintained full dosing or had a dose reduction for <70% of the treatment period.…”

“…When is the question The median DoT with sorafenib was 5.3 months in the Phase III SHARP trial and 3.8 and 3.4 months in the real-world SOFIA and GIDEON studies, respectively [6,[9][10], suggesting that www.futuremedicine.com in order to achieve the longest possible DoT, and with this, the best possible patient benefit.…”