IMbrave 151 missed primary endpoint in advanced BTC

Adding bevacizumab to atezolizumab plus cisplatin and gemcitabine did not significantly improve the progression-free survival (PFS) of patients with newly diagnosed, advanced biliary tract cancer (BTC), the phase 2 IMbrave 151 trial showed.

“The combination of the PD-L1 inhibitor atezolizumab and the VEGF inhibitor bevacizumab is the main standard-of-care for patients with unresectable hepatocellular carcinoma (HCC) [1],” explained Prof. Anthony El-Khoueiry (USC Norris Comprehensive Cancer Center, CA, USA). The phase 2 IMbrave151 study (NCT04677504) evaluated atezolizumab and bevacizumab in combination with chemotherapy in newly diagnosed patients with advanced BTC (n=162) [2].

Patients who were randomised to the experimental arm received 8 cycles of gemcitabine plus cisplatin chemotherapy and bevacizumab and atezolizumab until disease progression, unacceptable toxicity, or until there was no longer a clinical benefit. In the placebo arm, bevacizumab was replaced with placebo. PFS was the primary endpoint.

PFS was not significantly improved in the bevacizumab arm compared with the control arm, although the investigators noticed a numerical benefit of the experimental arm over the control arm (median PFS 8.3 months vs 7.9 months; HR 0.76; 95% CI 0.51–1.14, see Figure). The overall survival (OS) data displayed a similar trend (median OS ‘not reached’ vs 11.4 months; HR 0.74; 95% CI 0.43–1.27). Prof. El-Khoueiry mentioned that bevacizumab did not add substantial toxicity to the safety profile of the treatment regimen. The rates of grade 3 or 4 adverse events (AEs) during the chemotherapy phase were similar for the 2 treatment arms, with 69.2% and 70.4%. After the chemotherapy phase, these rates dropped to 31.5% in the bevacizumab arm and to 24.5% in the control arm. Finally, it was highlighted that any grade hypertension was more common in the bevacizumab arm than in the placebo arm (34.6% vs 16.0%).

Figure: Progression-free survival of bevacizumab-containing regimen versus placebo [2]

Atezo, atezolizumab; Bev, bevacizumab; CisGem, cisplatin and gemcitabine; PBO, placebo.

Although the results of the IMbrave 151 study showed a modest improvement in PFS with the addition of bevacizumab to atezolizumab and chemotherapy in patients with newly diagnosed advanced BTC, this finding did not reach statistical significance. The 2 arms were experimental with a small sample size.

1. Finn RS, et al. N Engl J Med. 2020;382:1894–1905.
2. El-Khoueiry AB, et al. IMbrave151: A phase 2, randomized, double-blind, placebo-controlled study of atezolizumab with or without bevacizumab in combination with cisplatin plus gemcitabine in patients with untreated, advanced biliary tract cancer. Abstract 491, ASCO GI 2023, 19–21 January, San Francisco, CA, USA.

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Posted on 17 March, 2023