Adjuvant regimen has ‘potential’ to change practice in high-risk liver cancer
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Key takeaways:
- Adjuvant atezolizumab and bevacizumab improved RFS compared with active surveillance.
- The combination exhibited a manageable safety profile.
Adjuvant treatment with atezolizumab and bevacizumab extended RFS compared with active surveillance among patients with hepatocellular carcinoma, according to study findings presented at AACR Annual Meeting.
The combination exhibited a generally manageable safety profile, results of the randomized phase 3 IMbrave050 trial showed.
The findings suggest the combination could be a new standard for adjuvant treatment of HCC, researchers concluded.
“Due to the lack of proven adjuvant therapy strategies for HCC, patients who are treated with surgical resection or thermal ablation with curative intent tend to have significantly higher recurrence rates and shorter overall survival than patients with other types of cancer — for example, colorectal [cancer or] breast cancer treated with similar curative intent,” Pierce Chow, FRCS(E), PhD — senior consultant surgeon at National Cancer Centre Singapore and Singapore General Hospital, as well as professor and program director at Duke-NUS Medical School in Singapore — said in a press release. “The positive results of IMBrave050 address this huge and urgent unmet clinical need in HCC.”
Background and methods
Surgical resection and thermal ablation are standard components of curative treatment for early-stage HCC. Most of these patients then undergo active surveillance.
However, as many as 80% of patients develop recurrence within 5 years of resection or curative-intent ablation, according to study background. Consequently, there is a need for more effective adjuvant treatments.
The combination of atezolizumab (Tecentriq, Genentech) — an anti-PD-L1 antibody — and bevacizumab (Avastin, Genentech), a humanized anti-vascular endothelial growth factor monoclonal antibody, is standard treatment for unresectable HCC based on OS, PFS and objective response rate results observed in the IMbrave 150 study.
In the IMbrave050 trial, Chow and colleagues assessed whether the atezolizumab-bevacizumab combination could prevent or delay recurrence compared with active surveillance for patients with high-risk HCC who underwent surgical resection or ablation.
The trial included 668 patients with HCC who underwent resection or ablation but remained at high risk for recurrence based on tumor burden, tumor differentiation and vascular invasion.
Researchers assigned 334 patients to 1,200 mg atezolizumab and 15 mg/kg bevacizumab via IV every 3 weeks for 1 year (17 cycles). The other 334 patients underwent active surveillance.
Patients assigned active surveillance who developed recurrence per independent review facility confirmation could switch to the experimental combination.
Groups appeared balanced with regard to baseline demographics.
RFS per independent review facility assessment served as the primary endpoint. Secondary endpoints included OS; investigator-assessed RFS; OS and RFS based on PD-L1 status; and time to extrahepatic spread or macrovascular invasion.
Researchers stratified by geographic region — Asia-Pacific region excluding Japan vs. the rest of the world — as well as a composite factor that encompassed the number of high-risk features, curative procedure and use of optional adjuvant transarterial chemoembolization, which was allowed for one cycle after resection.
Results
Chow presented results of an interim analysis conducted after median follow-up of 17.4 months.
Median RFS per independent review facility assessment had not been reached in either group.
However, the trial met its primary endpoint, with results showing the atezolizumab-bevacizumab regimen reduced risk for recurrence or death by 28% compared with active surveillance (HR = 0.72; 95% CI, 0.56-0.93). Results appeared generally consistent across clinical subgroups.
The investigator-assessed RFS yielded a similar result (HR = 0.7; 95% CI, 0.54-0.91).
The atezolizumab-bevacizumab combination exhibited a generally manageable safety profile consistent with prior reports with each agent, Chow and colleagues reported.
Patients in IMbrave050 remained on treatment longer than those in IMbrave150 (median atezolizumab treatment, 11.07 months vs. 7.4 months; median bevacizumab treatment, 11.02 months vs. 6.9 months).
However, despite the longer duration of therapy, incidence of serious therapy-related adverse events appeared comparable between the two trials. This supports the tolerability of the combination in the adjuvant setting, Chow said.
Researchers acknowledged study limitations, including the fact data from analyses of secondary endpoints — including OS — remained immature.
“IMbrave050 is a landmark study and the first to demonstrate an efficacious adjuvant therapy for patients with HCC who have undergone surgical resection or ablation,” Chow said in the release. “These results have established a benchmark in adjuvant therapy for HCC and have the potential to be practice-changing.”
The findings also may result in modifications to clinical indications for surgical resection and ablation for HCC, Chow said.
“Surgery is not offered to many patients with potentially resectable disease if rapid recurrence is expected based on tumor burden or the presence of vascular invasion,” Chow said. “The availability of an efficacious adjuvant therapy may lead to a reassessment of which patients may benefit from surgical resection.”
References:
- Adjuvant treatment with atezolizumab and bevacizumab may delay recurrence after surgical resection in patients with liver cancer (AACR press release). Published April 16, 2023. Accessed April 16, 2023.
- Chow P, et al. Abstract CT003. Presented at: American Association for Cancer Research Annual Meeting; April 14-19, 2023; Orlando.
Perspective
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Theodore H. Welling, MD
This is an interesting trial. We definitely need adjuvant treatment for patients with HCC at high risk for recurrence, such as those with vascular invasion. The findings are not exactly surprising. How much it changes practice remains uncertain. Although I don’t have the details, it appears patients were treated much longer than standard adjuvant course compared with other cancers — a long time to be on systemic therapy. In contrast, many patients who recur are able to be treated with other local therapies — such as ablation, radioembolization, surgery or even transplant — before systemic therapy is needed. Given these caveats, it will be important to see whether adjuvant therapy translates into improved OS.
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Chow P, et al. Abstract CT003. Presented at: American Association for Cancer Research Annual Meeting; April 14-19, 2023; Orlando.
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