SINGAPORE — An international randomized controlled trial has reported that the combination therapy of atezolizumab and bevacizumab in the adjuvant setting is safe and effective in reducing cancer recurrence in patients with hepatocellular carcinoma (HCC, or primary liver cancer), at high risk for recurrence after curative intent resection or ablation.
Liver cancer is the sixth most common cancer in the world and fourth most common cause of cancer deaths globally. In Singapore, HCC is the third most common cause of cancer deaths in males and fifth most common cause in females as it is usually diagnosed at a late stage when the prognosis is poor.
Liver resection or ablation, a process that uses heat or shock-freezing to destroy tumors, is a potential treatment option for HCC. Yet, 70 to 80 percent of patients experience cancer recurrence within five years of receiving these treatments. Currently, there is no recognized standard of care for adjuvant therapy in patients with HCC and so, clinical outcomes after curative intent liver resection and ablation in HCC are poorer than those of other common cancers.
The IMbrave050 trial
To address this significant unmet clinical need in HCC, IMbrave050, a global, open-label Phase 3 trial was conducted between 2019 and 2022 to evaluate the safety and efficacy of adjuvant atezolizumab and bevacizumab. A total of 668 patients with HCC at high risk of cancer recurrence after surgical resection or ablation were enrolled from 134 sites in 26 countries.
The age range of participants was between 51 and 68 years, with a median age of 58 years. 83 percent of the participants were male, 82 percent were Asian, and in around 62 percent of them, the main underlying cause of HCC was hepatitis B. Participants were randomly and equally divided into two groups, with one group receiving atezolizumab and bevacizumab and the other group put under active surveillance, which is the current standard of care after surgical resection and ablation. Participants in the treatment arm received intravenous atezolizumab and bevacizumab every three weeks for up to 12 months or 17 cycles.
Results of the IMbrave050 trial
Trial results were positive at the first analysis and showed a one-third decrease in cancer recurrence at the end of the first year. The risk of disease recurrence or death was 28 percent lower in the group who received adjuvant atezolizumab plus bevacizumab compared to the group who had undergone active surveillance. The safety profile of the adjuvant therapy was consistent with prior studies of atezolizumab and bevacizumab.
“The positive outcomes of IMbrave050 bring new hope to liver cancer patients. It is a landmark study and the first in the world to demonstrate an effective adjuvant therapy for patients with hepatocellular carcinoma. These results have the potential to be practice-changing and we are encouraged that they may lead to a reassessment of recommendations for surgical resection and the treatment of hepatocellular carcinoma,” said study corresponding author and IMbrave050 steering committee co-chair Pierce Chow, MBBS, MMed, FRCS, FAMS, PhD, professor and senior consultant surgeon at Singapore General Hospital and National Cancer Centre Singapore and professor at Duke-NUS Medical School.
The next steps for this combination therapy are further studies in a larger population and in curative settings for HCC. At the time of publication, three other trials of adjuvant immunotherapy after surgical resection or ablation of HCC were ongoing.
- This press release is supported by the National Cancer Centre Singapore