The frontline combination of atezolizumab and bevacizumab statistically and clinically improved progression-free survival and overall survival compared with sorafenib in patients with hepatocellular carcinoma in the phase III IMbrave150 study, according to a press release from Roche.
Levi Garraway, MD, PhD
The frontline combination of atezolizumab and bevacizumab statistically and clinically improved progression-free survival (PFS) and overall survival (OS) compared with sorafenib in patients with hepatocellular carcinoma (HCC) in the phase III IMbrave150 study (NCT03434379), according to a press release from Roche.1
With atezolizumab/bevacizumab the risk of death in patients with HCC was decreased by 42% (HR, 0.58; 95% CI, 0.42-0.79;P= 0.0006) and the PFS rate was 41% (HR, 0.59; 95% CI, 0.47-0.76;P<0.0001). The median OS was not reached in the combination arm and was 13.2 months with sorafenib alone. The median PFS in patients who received atezolizumab plus bevacizumab was 6.8 months compared with 4.3 months in the sorafenib group.
In the combination group, grade 3 and 4 adverse events (AEs) occurred in 57% of people, compared with 55% in the sorafenib group. In both arms, grade 5 AEs were seen in 5% and 6% of patients, respectively. These AEs were considered tolerable and were consistent with toxicities seen in either drug alone.
This combination is the first in 10 years to improve both OS and PFS compared to the standard of care (SoC), sorafenib.
“For the first time in a decade, we are seeing a treatment that has improved overall survival for people with unresectable hepatocellular carcinoma compared with the current standard of care,” said Levi Garraway, MD, PhD, chief medical officer and head of global product development, Roche, in the press release.
Participants in the phase II, open-label, randomized IMbrave150 study were randomized 2:1 to either receive combination therapy with intravenous atezolizumab 1200 mg on day 1 of each 21-day cycle and intravenous bevacizumab at 15 mg on day 1 of each 21-day cycle or 400 mg of SoC, twice per day.
One primary endpoint of the study was OS, per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, which was defined as randomization to the first occurrence of disease progression or all-cause death. The second primary endpoint was PFS, which was defined as randomization to death from any cause, through the end of the study. The key secondary endpoints of the study included objective response, time to progression, duration of response as measured by RECIST v1.1, and patient-reported outcomes.
Individuals with locally advanced or metastatic and/or unresectable HCC who had not received prior systemic therapy were eligible to enroll into the study granted these patients had 1 or more measurable lesion(s), an Eastern Cooperative Oncology Group performance score of 0 or 1, and adequate hematologic and end-organ function. Most of the exclusion criteria were related to existing comorbidities or previous conditions, some of which included, active or history of autoimmune disease or immune deficiency, history of leptomeningeal disease, active tuberculosis, known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma, history of cancer other than HCC within 5 years prior to screening, and a history of hepatic encephalopathy.
The FDA granted a breakthrough therapy designation to the combination of atezolizumab and bevacizumab in July 2018, as a treatment for patients with advanced or metastatic HCC, in the first-line setting. The designation was based on results from a phase Ib trial (NCT02715531), which evaluated the safety and efficacy of the combination in solid tumors.
“Tecentriq in combination with Avastin could transform the treatment of this aggressive disease, and we are working closely with global health authorities in the hope of bringing this treatment option to patients as soon as possible,” Garraway noted in his statement.
Results from the phase II IMbrave trial were presented at the European Society for Medical Oncology Asia Congress 2019. The investigators of the study concluded that atezolizumab plus bevacizumab is a promising first-line combination offering a new option for patients with unresectable HCC.
The study is ongoing with 164 patients currently enrolled. Patients are actively being recruited to meet the goal of 480 participants. The prospective completion date is June 2022.