Safety and efficacy of cabozantinib for patients with advanced hepatocellular carcinoma who advanced to Child-Pugh B liver function at study week 8: a retrospective analysis of the CELESTIAL randomised controlled trial

Background: Patients with hepatocellular carcinoma (HCC) and Child–Pugh B liver cirrhosis have poor prognosis and are underrepresented in clinical trials. The CELESTIAL trial, in which cabozantinib improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with HCC and Child–Pugh A liver cirrhosis at baseline, was evaluated for outcomes in patients who had Child–Pugh B cirrhosis at Week 8. Methods: This was a retrospective analysis of adult patients with previously treated advanced HCC. Child–Pugh B status was assessed by the investigator. Patients were randomised 2:1 to cabozantinib (60 mg once daily) or placebo. Results: Fifty-one patients receiving cabozantinib and 22 receiving placebo had Child–Pugh B cirrhosis at Week 8. Safety and tolerability of cabozantinib for the Child–Pugh B subgroup were consistent with the overall population. For cabozantinib- versus placebo-treated patients, median OS from randomisation was 8.5 versus 3.8 months (HR 0.32, 95% CI 0.18–0.58), median PFS was 3.7 versus 1.9 months (HR 0.44, 95% CI 0.25–0.76), and best response was stable disease in 57% versus 23% of patients. Conclusions: These encouraging results with cabozantinib support the initiation of prospective studies in patients with advanced HCC and Child–Pugh B liver function. Clinical Trial Registration: NCT01908426

Safety and efficacy of cabozantinib for patients with advanced hepatocellular carcinoma who advanced to Child-Pugh B liver function at study week 8: a retrospective analysis of the CELESTIAL randomised controlled trial.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) and Child-Pugh B liver cirrhosis have poor prognosis and are underrepresented in clinical trials. The CELESTIAL trial, in which cabozantinib improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with HCC and Child-Pugh A liver cirrhosis at baseline, was evaluated for outcomes in patients who had Child-Pugh B cirrhosis at Week 8. METHODS: This was a retrospective analysis of adult patients with previously treated advanced HCC. Child-Pugh B status was assessed by the investigator. Patients were randomised 2:1 to cabozantinib (60 mg once daily) or placebo. RESULTS: Fifty-one patients receiving cabozantinib and 22 receiving placebo had Child-Pugh B cirrhosis at Week 8. Safety and tolerability of cabozantinib for the Child-Pugh B subgroup were consistent with the overall population. For cabozantinib- versus placebo-treated patients, median OS from randomisation was 8.5 versus 3.8 months (HR 0.32, 95% CI 0.18-0.58), median PFS was 3.7 versus 1.9 months (HR 0.44, 95% CI 0.25-0.76), and best response was stable disease in 57% versus 23% of patients. CONCLUSIONS: These encouraging results with cabozantinib support the initiation of prospective studies in patients with advanced HCC and Child-Pugh B liver function. CLINICAL TRIAL REGISTRATION: NCT01908426

Multicenter, double-blind, placebo-controlled study of the use of filgrastim in patients hospitalized with pneumonia and severe sepsis

To determine the safety and efficacy of filgrastim (r-metHuG-CSF) in combination with intravenous antibiotics to reduce the rate of mortality in patients with pneumonia and sepsis.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial

Objective In the phase 3 CELESTIAL trial, cabozantinib improved overall survival (OS) and progression-free survival (PFS) compared with placebo in patients with previously treated advanced hepatocellular carcinoma (HCC). This subgroup analysis evaluated cabozantinib in patients who had received sorafenib as the only prior systemic therapy. Methods CELESTIAL randomised (2:1) patients with advanced HCC and Child-Pugh class A liver function to treatment with cabozantinib (60 mg daily) or placebo. Eligibility required prior treatment with sorafenib, and patients could have received ≤2 prior systemic regimens. The primary endpoint was OS. Outcomes in patients who had received sorafenib as the only prior therapy were analysed by duration of prior sorafenib (<3 months, 3 to <6 months and ≥6 months). Results Of patients who had received only prior sorafenib, 331 were randomised to cabozantinib and 164 to placebo; 136 patients had received sorafenib for <3 months, 141 for 3 to <6 months and 217 for ≥6 months. Cabozantinib improved OS relative to placebo in the overall secondline population who had received only prior sorafenib (median 11.3 vs 7.2 months; HR=0.70, 95% CI 0.55 to 0.88). This improvement was maintained in analyses by prior sorafenib duration with longer duration generally corresponding to longer median OS-median OS 8.9 vs 6.9 months (HR=0.72, 95% CI 0.47 to 1.10) for prior sorafenib <3 months, 11.5 vs 6.5 months (HR=0.65, 95% CI 0.43 to 1.00) for 3 to <6 months and 12.3 vs 9.2 months (HR=0.82, 95% CI 0.58 to 1.16) for ≥6 months. Cabozantinib also improved PFS in all duration subgroups. Safety data were consistent with the overall study population. Conclusion Cabozantinib improved efficacy outcomes versus placebo in the second-line population who had received only prior sorafenib irrespective of duration of prior sorafenib treatment, further supporting the utility of cabozantinib in the evolving treatment landscape of HCC. Clinical trial number NCT01908426

Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial.

In the phase 3 CELESTIAL trial, cabozantinib improved overall survival (OS) and progression-free survival (PFS) compared with placebo in patients with previously treated advanced hepatocellular carcinoma (HCC). This subgroup analysis evaluated cabozantinib in patients who had received sorafenib as the only prior systemic therapy. CELESTIAL randomised (2:1) patients with advanced HCC and Child-Pugh class A liver function to treatment with cabozantinib (60 mg daily) or placebo. Eligibility required prior treatment with sorafenib, and patients could have received ≤2 prior systemic regimens. The primary endpoint was OS. Outcomes in patients who had received sorafenib as the only prior therapy were analysed by duration of prior sorafenib (&lt;3 months, 3 to &lt;6 months and ≥6 months). Of patients who had received only prior sorafenib, 331 were randomised to cabozantinib and 164 to placebo; 136 patients had received sorafenib for &lt;3 months, 141 for 3 to &lt;6 months and 217 for ≥6 months. Cabozantinib improved OS relative to placebo in the overall second-line population who had received only prior sorafenib (median 11.3 vs 7.2 months; HR=0.70, 95% CI 0.55 to 0.88). This improvement was maintained in analyses by prior sorafenib duration with longer duration generally corresponding to longer median OS-median OS 8.9 vs 6.9 months (HR=0.72, 95% CI 0.47 to 1.10) for prior sorafenib &lt;3 months, 11.5 vs 6.5 months (HR=0.65, 95% CI 0.43 to 1.00) for 3 to &lt;6 months and 12.3 vs 9.2 months (HR=0.82, 95% CI 0.58 to 1.16) for ≥6 months. Cabozantinib also improved PFS in all duration subgroups. Safety data were consistent with the overall study population. Cabozantinib improved efficacy outcomes versus placebo in the second-line population who had received only prior sorafenib irrespective of duration of prior sorafenib treatment, further supporting the utility of cabozantinib in the evolving treatment landscape of HCC. NCT01908426