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The China National Medical Products Administration has approved the combination of atezolizumab plus bevacizumab for use in patients with unresectable hepatocellular carcinoma who have not received previous systemic therapy.
The China National Medical Products Administration has approved the combination of atezolizumab (Tecentriq) plus bevacizumab (Avastin) for use in patients with unresectable hepatocellular carcinoma (HCC) who have not received previous systemic therapy.1
The regulatory decision was based on data from the phase 3 IMbrave150 trial, which analyzed a cohort comprised of 194 Chinese patients. Findings from this subset proved to be comparable to the global results that had been reported, according to Roche. In this patient population, atezolizumab/bevacizumab resulted in a 56% reduction in the risk of death (HR, 0.44; 95% CI, 0.25-0.76) and a 40% reduction in the risk of disease progression or death (HR, 0.60; 95% CI, 0.40-0.90) versus sorafenib (Nexavar).
“[The] approval of [atezolizumab] in combination with [bevacizumab] for unresectable HCC means that people in China now have a cancer immunotherapy option which is changing the treatment landscape for this aggressive disease,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, stated in a press release. “With almost half of the world’s HCC cases diagnosed in China, this approval marks a major advance for Chinese patients.”
Previously, in May 2020, the FDA approved atezolizumab plus bevacizumab for the same indication based on global data from the trial. Results showed a 42% reduction in the risk of death with the combination compared with sorafenib (HR, 0.58; 95% CI, 0.42-0.79; P =.0006).2 Atezolizumab/bevacizumab also led to a 41% reduction in the risk of disease progression or death versus sorafenib (HR, 0.59; 95% CI, 0.47-0.76; P <.0001).
In the international, multicenter, open-label, phase 3 trial, a total of 501 patients with unresectable HCC who had no received previous systemic treatment were randomized in a 2:1 fashion to receive either atezolizumab/bevacizumab or single-agent sorafenib.
In the experimental arm, the PD-L1 agent was given intravenously (IV) at a dose of 1200 mg on day 1 of each 21-day cycle and IV bevacizumab was given at a dose of 15 mg/kg on day 1 of each 21-day cycle. In the control arm, oral sorafenib was administered at a dose of 400 mg twice daily on days 1 to 21 of each 21-day cycle. Treatment was administered until either intolerable toxicity or loss of clinical benefit as determined by investigator assessment.
In order to participate, patients had to have locally advanced or metastatic and/or unresectable HCC; they could not have received any previous systemic therapy. To be eligible, they had to have 1 or more measurable lesion, an ECOG performance status ranging from 0 to 1, acceptable hematologic and end-organ function, and Child-Pugh class A disease.
They could not participate 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. Moreover, if they had active history of autoimmune disease or an immune deficiency, active tuberculosis, a history of cancer other than HCC within 5 years before screening, known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC, they were excluded from enrollment. Those with a history of hepatic encephalopathy were also ineligible for inclusion.
The coprimary end points of the trial included overall survival and progression-free survival per an independent review facility (IRF) in accordance with RECIST v1.1 criteria. Key secondary end points comprised overall response rate (ORR), time to disease progression, and duration of response per RECIST v1.1 criteria (investigator-assessed and IRF), HCC mRECIST (IRF), patient-reported outcomes, safety, and pharmacokinetics.
The data, presented during the 2019 ESMO Asia Congress, showed that grade 3/4 toxicities were reported in 57% of those who received the combination versus 55% in those who were given sorafenib.3 Moreover, the mortality rates in the investigational and control arms were 5% versus 6%, respectively. The most frequently reported serious toxicities included bleeding in the gastrointestinal tract and fever.4
“In China, primary liver cancer ranks as the fourth most common malignancy and is the second leading cause of cancer death. With most patients diagnosed at the intermediate and advanced stages where surgery or other locoregional therapies are not an option, there is an urgent need for effective treatments for unresectable HCC,” Professor Shukui Qin, MD, PhD, leading principal investigator of IMbrave150 in China and chairman of the Liver Cancer Expert Committee of the Chinese Society of Clinical Oncology (CSCO).
“The IMbrave150 study demonstrated that the combination of [atezolizumab] and [bevacizumab] in this setting can significantly improve outcomes for patients,” added Qin. “It is truly gratifying news that the combination is now approved in China and gives a new option to Chinese [patients with] liver cancer.”
In September 2020, the combination was recommended for approval by the European Medicine’s Agency’s Committee for Medicinal Products for Human Use for use in adult patients with advanced or unresectable hepatocellular carcinoma who had not been given previous systemic therapy. Atezolizumab/bevacizumab is also recommended as the preferred option for the treatment of patients with unresectable HCC by CSCO, according to Roche.