A combination of the immunotherapy drug Tecentriq (atezolizumab) and the targeted therapy Avastin 

(bevacizumab) improved quality of life and delayed worsening of symptoms in people with advanced liver cancer, according to a report presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in San Francisco.

The patient experience with treatment was a key theme of this year’s meeting, as the cancer field increasingly recognizes the importance of not only extending life, but also ensuring that its quality is maintained.

"Patient-reported outcomes, or PROs, are now recognized as important endpoints of cancer clinical trials that provide important insights regarding the impact of treatment on patients’ quality of life," ASCO chief medical officer and executive vice president Richard Schilsky, MD, said in a press release. "PROs inform us about the tolerability of new therapies, which is just as important as efficacy in gauging their utility and acceptance by patients."

Over years or decades, chronic hepatitis B or C, heavy alcohol use, fatty liver disease and other causes can lead to the development of liver cirrhosis and hepatocellular carcinoma (HCC), the most common type of liver cancer. HCC is often detected late and is difficult to treat, making it one of the leading causes of cancer death.

Peter Galle, MD, PhD, of the University Medical Center in Mainz, Germany presented patient-reported outcomes from the Phase III IMbrave150 trial, which compared Tecentriq plus Avastin versus standard treatment using the targeted therapy Nexavar (sorafenib).

Tecentriq is a PD-L1 checkpoint inhibitor that restores T-cell activity against cancer. Avastin is a monoclonal antibody that blocks VEGF, a protein that promotes the proliferation of blood vessels that supply tumors and plays a role in immune suppression.

“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,” Galle said. “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.”

IMbrave included 501 people with inoperable locally advanced or metastatic HCC who had not yet received systemic treatment. They were randomly assigned to take Tecentriq plus Avastin, both administered by IV infusion every three weeks, or twice-daily oral Nexavar until they experienced disease progression or unacceptable side effects.

Primary results from the study were presented at the European Society for Medical Oncology Asia Congress in November. Tecentriq plus Avastin reduced the risk of disease progression or death by 41% (median 6.8 versus 4.3 months). Overall survival was 13.2 months in the Nexavar group but was not reached in the combination group because most patients were still alive. Overall response rates, meaning complete or partial tumor shrinkage, were 27% versus 12%, respectively.

Looking at side effects, people taking Tecentriq plus Avastin were more likely to experience fever, abnormal liver and kidney biomarkers and infusion reactions, while those taking Nexavar had more diarrhea and hand-foot syndrome (redness, swelling and pain on the palms of the hands and soles of the feet). 

At the recent conference, Galle presented details about patient experiences during the trial. Participants were asked to complete questionnaires every three weeks during treatment and every three months after discontinuation for a year.

The surveys asked about quality of life, physical functioning and role functioning, or how well people were able to perform their usual social and occupational activities. Clinically meaningful deterioration was defined as a decrease of 10 or more points on a 100-point scale. More than 90% of people in both treatment groups completed the questionnaires through most of the treatment period.

About 30% of Tecentriq plus Avastin recipients reported a clinically meaningful decline in their quality of life, compared with about 30% of Nexavar recipients. What’s more, the time to deterioration was substantially longer for those taking the combination (11.2 versus 3.6 months, respectively).

Physical functioning showed a similar pattern. About 23% of Tecentriq plus Avastin recipients reported a meaningful decline versus about 37% of Nexavar recipients. Here too, the time to deterioration was longer in the former group (13.1 versus 4.9 months, respectively).

Turning to role functioning, about 29% of Tecentriq plus Avastin recipients and about 38% of Nexavar recipients reported a meaningful decline, and the time to deterioration was again longer in the former group (9.1 versus 3.6 months, respectively).

Finally, Tecentriq plus Avastin recipients reported a longer period before they experienced worsening of symptoms including loss of appetite, diarrhea, fatigue and pain.

"High-quality patient-reported outcome data demonstrate clinical meaningful benefits in key aspects of the patient experience (quality of life, functioning, key symptoms) with atezolizumab plus bevacizumab versus sorafenib," the researchers concluded.

Editor’s note: On January 27, Genentech announced that it has submitted a supplemental biologics license application to the Food and Drug Administration for the approval of Tecentriq plus Avastin for people with unresectable HCC.

Click here to read the study abstract.

Click here to learn more about liver cancer.