This article is more than 5 years old. Information may no longer be current.
Everolimus failed to improve OS in advanced HCC
Click Here to Manage Email Alerts
Patients with advanced hepatocellular carcinoma who were intolerant to or experienced disease progression on sorafenib did not derive an OS benefit from everolimus, according to results of the phase 3 EVOLVE-1 trial.
Andrew X. Zhu, MD, PhD, director of liver cancer research at Massachusetts General Hospital, and colleagues evaluated data from 546 adults with Barcelona Clinical Liver Cancer stage B or C HCC and Child-Pugh A liver function. All patients either were intolerant to sorafenib (Nexavar, Bayer), or experienced disease progression during or after sorafenib treatment.
Zhu and colleagues randomly assigned 362 patients to 7.5 mg daily everolimus (Afinitor, Novartis). The other 184 patients received placebo. All patients received best supportive care.
Median follow-up from randomization was 24.6 months (range, 14.8-36.6). Median duration of everolimus exposure was 9.43 weeks (range, 0.1-120), and median duration of placebo exposure was 8.93 weeks (range, 0.4-136.3).
A similar percentage of patients in both arms died during follow-up (83.7% for everolimus vs. 82.1% for placebo; HR=1.05; 95% CI, 0.86-1.27). Median OS also was comparable between arms (7.6 months for everolimus vs. 7.3 months for placebo). A majority of deaths in the everolimus (91.4%) and placebo (94.7%) arms were due to disease progression.
The median time to progression was 3 months in the everolimus arm and 2.6 months in the placebo arm (HR=0.93; 95% CI, 0.75-1.15). However, researchers reported a higher disease control rate in the everolimus arm (56.1% vs. 45.1%; P=.01).
Researchers reported higher rates of grade 3 to grade 4 anemia (7.8% vs. 3.3%), asthenia (7.8% vs. 5.5%) and decreased appetite (6.1% vs. 0.5%) in the everolimus arm. Twenty-nine patients assigned everolimus and 10 assigned placebo experienced asymptomatic hepatitis B viral reactivation. This led to everolimus discontinuation in three patients. No patients experienced hepatitis C viral flare.
Despite the study’s failure to meet its primary endpoint, lessons can still be derived from the data, according to researchers.
“First, it’s difficult to assess efficacy signals from phase 2 trials,” Zhu and colleagues wrote. “For everolimus, the initial modest efficacy signal was obtained from two phase 1/phase 2 studies. As has been recommended, assessing efficacy in a randomized phase 2 study should be considered before proceeding to phase 3 testing. Second, surrogate endpoints — such as time to progression, PFS and response rate — inconsistently predict OS in phase 3 trials. Third, clinical and biological heterogeneity likely affects the performance of targeted therapies in HCC. Future studies of targeted agents for HCC should aim to enrich patient populations based on molecular classification and predictive biomarkers.”
Disclosure: See the study for a full list of the researchers’ relevant financial disclosures.
Click Here to Manage Email Alerts