GI cancer

Promising results with dual blockade of PDL-1 and VEGF in unresectable HCC

Atezolizumab in combination with bevacizumab is a promising first-line treatment option for people with unresectable hepatocellular carcinoma, ESMO 2019 delegates have heard.

Presenting the results of the Phase 1b GO30140 study as a late breaking abstract Dr Michael Lee, MD, of the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, said the current standard of care for people with unresectable HCC was VEGFR tyrosine kinase inhibitors that were associated with modest survival benefits and toxicities.

“Single agent PD-L1/ PD-1 immune checkpoint inhibitors have demonstrated activity [in HCC] but have so far failed to demonstrate superiority in randomised studies of HCC… while dual blockade of PDL-1 and VEGF has shown clinical benefit in other tumour types,” he said.

The current study was the first randomised analysis of an immune checkpoint inhibitor plus a VEGF inhibitor versus an immune checkpoint inhibitor alone.

All patients in arm A received atezolizumab and bevacizumab (n=104). Patients in arm F were randomised 1:1 to receive atezolizumab and bevacizumab (n=60) or atezolizumab monotherapy (n=59).

Patients on the combination received atezolizumab 1200 mg and bevacizumab 15 mg/kg intravenously every three weeks, while those in the monotherapy cohort received atezolizumab 1200 mg intravenously every three  weeks.

In all cohorts, treatment continued until unacceptable toxicity or loss of clinical benefit. Primary endpoints were progression free survival (PFS; arm F) and objective response rate (ORR, arm A) by independent review facility (IRF)-assessed RECIST 1.1, and safety (arms F and A).

Median duration of follow-up was 12.4 months in arm A and 6.6 months in arm F.

Results showed that in arm A, the primary endpoint of confirmed ORR by IRF RECIST 1.1 was 36% (37 patients) with 76% of responses ongoing.

Data from arm F demonstrated the superiority of the combination of atezolizumab and bevacizumab over atezolizumab monotherapy (PFS HR 0.55; 80% CI 0.40-0.74, P=0.0108).

Dr Lee noted that in both arms the combination of atezolizumab and bevacizumab was generally well tolerated and side effects were manageable.

“No new safety signals were identified beyond the safety profile of each single agent,” he said.

“Atezolizumab in combination with bevacizumab may become a promising treatment option for patients with unresectable HCC,” Dr Lee concluded, adding that the combination was currently being evaluated in the Phase III IMbrave study.

Invited discussant Professor Arndt Vogel, a professor of gastrointestinal oncology from Hannover, Germany, said the trial showed an impressive ORR / CR rate in a more advanced 1st line population and there was a clear signal to proceed to Phase III, which will be reported soon.

However, he noted that it was not yet clear whether the effects of the combination therapy were synergistic or additive.

According to Professor Vogel the questions that needed to be answered were, “can bevacizumab really turn cold tumours into hot tumours? and who needs to be treated with the doublet with respect to the risk-benefit balance?”.

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