Atezolizumab in Combination with Bevacizumab May Be Effective for Patients with HCC

January 22, 2020

High-quality patient reported outcomes were observed, suggesting benefits in key aspects of the patient experience with this combination treatment.

High-quality patient reported outcomes from IMbrave 150 suggested large and consistent benefits in key aspects of the patient experience with atezolizumab (Tecentriq) plus bevacizumab (Avastin), according to an abstract published in the Journal of Clinical Oncology.1

The results, which will be presented at the 2020 Gastrointestinal Cancers Symposium, being held from January 23-25, in San Francisco, California, further support the overall clinical benefit of the drugs in patients with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy. 

“Because it reflects both the effects of disease and the side effects of treatment, sustained or improved quality of life is particularly important for patients,” lead author Peter R. Galle, MD, PhD, from the University Medical Center in Mainz, Germany, said in a press release.2 “Patients with liver cancer are typically more fragile and frail than others. Toxicity of the treatments can be much more serious for these patients, and their quality of life can decline quite quickly.”

The phase III study randomized patients 2:1 to receive either atezolizumab plus bevacizumab or sorafenib (Nexavar) alone as a first-line treatment. At baseline, every 3 weeks during therapy, and every 3 months after discontinuation of therapy, patients completed 2 questionnaires (1 HCC specific) to assess quality of life, physical functioning, and role functioning. Questionnaire completion rates were about 92%.

The primary endpoint for the study was overall survival, which was presented at the European Society for Medical Oncology (ESMO) Asia Congress in November 2019. At the time, the median overall survival had not been reached for atezolizumab plus bevacizumab compared with the overall survival of 13.2 months seen in patients receiving sorafenib alone. The overall response rate was 27% with atezolizumab plus bevacizumab and 12% for the patients receiving sorafenib.

Time to deterioration, defined as a decrease of 10 points from baseline in key patient-reported outcomes, was a prespecified secondary endpoint of the study assessed by two validated patient-reported quality of life tools. Time to deterioration was a median of 11.2 months in the patients receiving atezolizumab in combination with bevacizumab and 3.6 months in the patients treated with sorafenib (HR, 0.63; 95% CI, 0.46-0.85). 

Declines in physical functioning and role functioning were also delayed with the combination treatment, with a median delay of 13.1 months observed with atezolizumab and bevacizumab compared with 4.9 months for sorafenib (HR, 0.53; 95% CI, 0.39-0.73) in physical functioning, and a median delay of 9.2 months for the combination treatment compared to 3.6 months for the sorafenib (HR, 0.62; 95% CI, 0.46-0.84) observed in role functioning.

Additionally, atezolizumab and bevacizumab delayed time to deterioration in patient reported appetite loss, fatigue, pain, and diarrhea vs sorafenib, with a lower proportion of patients on the combination treatment experiencing clinically meaningful deterioration in each of these symptoms.

According to a 2018 article published by Contemporary Oncology, HCC is not only the most common primary cancer of the liver, but it also represents the fastest rising cause of cancer-related deaths in the US.3 The disease accounts for 75-85% of primary liver cancers and is the second leading cause of cancer death in East Asia and sub-Saharan Africa and the sixth most common in western countries. 

References:

1. Galle PR, Finn RS, Qin S, et al. Patient-reported outcomes (PROs) from the Phase III IMbrave150 trial of atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (sor) as first-line treatment (tx) for patients (pts) with unresectable hepatocellular carcinoma (HCC). J Clin Oncol. NCT03434379.

2. New Drug Combinations Maintain Quality of Life for Patients With Colorectal and Liver Cancers [news release]. Alexandria, Virginia. Published January 21, 2020. asco.org/about-asco/press-center/news-releases/new-drug-combinations-maintain-quality-life-patients. Accessed January 22, 2020. 

3. Rawla P, Sunkara T, Muralidharan P, Raj JP. Update in global trends and aetiology of hepatocellular carcinoma. Contemp Oncol (Pozn). doi:10.5114/wo.2018.78941.