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The European Commission has approved the combination of atezolizumab plus bevacizumab for use in adult patients with advanced or unresectable hepatocellular carcinoma who have not been given previous systemic therapy.
The European Commission has approved the combination of atezolizumab (Tecentriq) plus bevacizumab (Avastin) for use in adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have not been given previous systemic therapy.1
With this approval, atezolizumab/bevacizumab is the first immunotherapy regimen to receive approval in Europe for patients with unresectable HCC, according to Roche.
The decision was based on findings from the pivotal phase 3 IMbrave150 trial, which showed a 42% reduction in the risk of death with atezolizumab/bevacizumab versus sorafenib (Nexavar), which translated to a hazard ratio (HR) of 0.58 (95% CI, 0.42-0.79; P =.0006).2 The doublet also reduced the risk of disease progression or death by 41% compared with sorafenib (HR, 0.59; 95% CI, 0.47-0.76; P <.0001).
“[Atezolizumab] in combination with [bevacizumab] is the first treatment to be approved in over a decade that has improved overall survival (OS) for people with previously untreated advanced or unresectable HCC,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, stated in a press release. “We’re delighted that people in Europe can now benefit from this combination and we look forward to working with individual countries within the [European Union] to ensure people access the combination as soon as possible.”
In the international, multicenter, open-label, phase 3 IMbrave150 trial, 501 patients with unresectable HCC who had not received any prior systemic therapy were randomized 2:1 to either atezolizumab/bevacizumab or sorafenib. In the investigational arm, participants received 1200 mg of atezolizumab intravenously (IV) on day 1 of each 21-day cycle; they also received 400 mg of IV bevacizumab twice daily on days 1 through 21 of each 21-day treatment cycle. Participants were given treatment until either unacceptable toxicity or loss of clinical benefit per investigator assessment.
To be eligible for inclusion, patients had to have locally advanced or metastatic and/or unresectable HCC and they could not have previously received systemic therapy. Moreover, patients had to have 1 or more measurable lesion, an ECOG performance status of 0 or 1, adequate hematologic and end-organ function, and Child-Pugh class A disease.
If they had a history of leptomeningeal disease or a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan, they could not participate. Anyone with an active history of autoimmune disease or an immune deficiency, active tuberculosis, a history of cancer beyond HCC within 5 years prior to screening, or known fibrolamellar HCC, were not included. Patients with a history of hepatic encephalopathy were also determined to be ineligible.
OS and progression-free survival (PFS) via an independent review facility (IRF) per RECIST v1.1 criteria served as the coprimary end points of the trial. Secondary objectives included overall response rate (ORR), time to progressive disease, and duration of response via RECIST v1.1 criteria (investigator-assessed and IRF) HCC mRECIST (IRF), patient-reported outcomes, safety, and pharmacokinetics.
With regard to safety, grade 3/4 toxicities occurred in 57% versus 55% in those who received the combination versus sorafenib, respectively.3 Additionally, the mortality rate in the investigational arm was 5% versus 6% in the control arm. The most commonly experienced serious toxicities were comprised of fever and bleeding in the gastrointestinal tract.4
“The results of the IMbrave150 study mark a breakthrough in the treatment of advanced liver cancer, one of the few cancers with a rising death rate and limited options in the first-line setting,” Arndt Vogel, MD, professor of medicine at Hannover Medical School, added in the release. “After many failures in the last 12 years, the combination of [atezolizumab] and [bevacizumab] shows improvement in OS compared to sorafenib and offers patients the opportunity for improved disease control with high ORR.”
In May 2020, the FDA approved atezolizumab plus bevacizumab for the treatment of patients with unresectable or metastatic HCC who have not received prior systemic therapy based on data from IMbrave150. More recently, in October 2020, the China National Medical Products Administration approved the combination for the same indication.
The doublet is now approved for use in a total of 59 countries for patients with unresectable HCC, according to Roche. Moreover, ESMO recently included the combination as a class 1, A recommendation for the treatment of patients with unresectable HCC; atezolizumab/bevacizumab has also been recommended by other global clinical practice guidelines.
1. European Commission approves Roche’s Tecentriq in combination with Avastin for the treatment of people with the most common form of liver cancer. News release. Roche. November 2, 2020. Accessed November 2, 2020. https://bit.ly/3mQ36FL.
2. FDA approves Genentech’s Tecentriq in combination with Avastin for people with the most Common form of liver cancer. News release. Genentech. May 29, 2020. Accessed November 2, 2020. https://bit.ly/2Aneztc.
3. Genentech presents pivotal data demonstrating Tecentriq in combination with Avastin improves overall survival in people with the most common form of liver cancer. News release. Genentech. November 22, 2019. Accessed November 2, 2020. https://bit.ly/35rZfGc.
4. Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894-1905. doi:10.1056/NEJMoa1915745