The mixture of a tyrosine kinase inhibitor with an immune checkpoint inhibitor considerably improved progression-free survival in sufferers with hepatocellular carcinoma, exhibits a brand new examine.
While the mix has been proven to be helpful in renal cell carcinoma and different strong tumor sorts, it has by no means earlier than been examined in a part 3 medical trial for hepatocellular carcinoma till now.
The new examine, revealed in The Lancet Oncology, included 837 sufferers from 178 hospital in 32 nations who had been enrolled within the examine (known as COSMIC-312) between December 2018 and August 2020. 432 sufferers had been randomly assigned to obtain a mix of cabozantinib (Cabometyx, Exelixis), a tyrosine kinase inhibitor (TKI), and atezolizumab (Tecentriq, Genentech), a PD-L1 inhibitor. While 217 sufferers had been handled with sorafenib (Nexavar, Bayer) alone and 188 sufferers had been handled with cabozantinib.
Clinically significant enhancements in progression-free survival, elevated illness management and decrease main development had been seen in sufferers who obtained the cabozantinib and atezolizumab mixture remedy over sufferers who had been handled with sorafenib. However, there was no enchancment in total survival.
“The improvement in progression-free survival with cabozantinib plus atezolizumab in this study shows that the combination confers clinical benefit for patients with advanced hepatocellular carcinoma previously untreated with systemic anticancer therapy,” wrote the authors of the examine, led by Robin Kate Kelley, MD, a gastrointestinal oncologist with the University of California, San Francisco, and Lorenza Rimassa, MD, a gastrointestinal oncologist with Humanitas University, Milan. “The absence of a benefit in overall survival, along with the availability of atezolizumab in combination with bevacizumab, indicates the need for additional studies to determine if cabozantinib plus atezolizumab would be an appropriate first-line treatment option in select patient populations.”
For symptomatic sufferers with excessive illness burden or important portal vein occlusion who’re in danger for impending problems, controlling the illness as shortly as attainable is significant, the authors wrote. “Underlying chronic liver disease is nearly universal in patients with hepatocellular carcinoma and the risk of gastrointestinal bleeding is high in this population, particularly if portal vein tumor thrombus is present.”
Hepatocellular carcinoma (HCC) is an angiogenic tumor, making it a logical goal for TKIs that focus on vascular endothelial development issue. The TKI sorafenib was the primary to be accepted as a first-line therapy for HCC, and since then immune checkpoint inhibitors have been proven to induce sturdy responses within the first-line setting, however haven’t improved total survival in randomized trials.
In the examine, after a median follow-up of 15.8 months, median progression-free survival was 6.8 months within the mixture group and 4.2 months within the sorafenib group (hazard ratio, 0.63; P = .0012). The median total survival was 15.4 months within the mixture group and 15.5 months within the sorafenib group (not vital).
Grade 3-4 opposed occasions included a rise in ALT, which occurred in 9% of the mix group, 3% of the sorafenib group, and 6% of the cabozantinib solely group; hypertension (9%, 8%, and 12%, respectively); a rise in AST improve (9%, 4%, 10%); and palmar-plantar erythrodysesthesia (8%, 8%, 9%). Serious treatment-related opposed occasions occurred in 18% of sufferers within the mixture arm, 8% within the sorafenib arm, and 13% within the cabozantinib arm.
There had been no extra severe bleeding occasions within the therapy teams containing cabozantinib, in contrast with sorafenib which is noteworthy as a result of HCC sufferers are at excessive danger for gastrointestinal bleeding.
Treatment-related grade 5 occasions had been uncommon, occurring in 1% (six sufferers) of the mix group, and in only one affected person in each the sorafenib and cabozantinib teams.
Although the outcomes counsel promising medical profit, the shortage of total survival profit restrict the implications of those findings. Since atezolizumab mixed with bevacizumab can be out there for this affected person inhabitants, extra analysis is required to find out if cabozantinib plus atezolizumab can grow to be a first-line choice.
The examine had some limitations: Participants needed to have a Child-Pugh class of A, although there was no requirement to evaluate for fibrosis or cirrhosis. Otherwise there have been few obstacles to check entry.
The examine was sponsored by Exelixis (Alameda) and Ipsen (Boulogne-Billancourt, France).
This article initially appeared on MDedge.com, a part of the Medscape Professional Network.