The U.S. Food and Drug Administration has granted breakthrough therapy designation to a combination of Tecentriq (atezolizumab) and Avastin (bevacizumab) for the first-line treatment of patients with advanced or metastatic hepatocellular carcinoma (HCC), the most common form of liver cancer.
The designation is expected to facilitate the development and regulatory review of this combination, and to expedite its approval and delivery to patients.
Tecentriq and Avastin are antibodies made by Genentech. Tecentriq works by targeting the PD-L1 protein, which gives a boost to cancer-fighting T-cells. Avastin disrupts the tumor blood supply by binding the VEGF protein.
Preliminary data from a Phase 1b clinical trial (NCT02715531) have supported the decision. The study is currently testing multiple immunotherapy combinations in a range of solid tumors. One arm is testing a combination of Tecentriq and Avastin as a first-line treatment for hepatocellular carcinoma patients whose disease is inoperable or has spread to distant organs. That trial is still recruiting participants.
After a median follow-up of 10.3 months, 63 percent of patients (15 of 23) responded to the treatment with a partial tumor reduction. Responses were seen in all subgroups of patients, regardless of disease origin and the presence of metastasis.
At this point, researchers were unable to determine progression-free survival (the time a patient lives without disease worsening), duration of response, time to progression, and overall survival, as less than half of patients had reached these objectives.
In a population that lives between 4.3 and 13.7 months with other Avastin combinations, and only 2.3 to 7.2 months without disease progression, this appears to be a remarkable achievement for the Avastin-Tecentriq combination.
From a total of 43 patients eligible for safety evaluation, 28 percent experienced severe to life-threatening treatment-related adverse side effects. No new safety concerns were raised beyond those previously described for each therapy. No fatalities caused by adverse reactions to the therapy were reported.
The results were presented during the 2018 ASCO annual meeting in a poster titled “Safety and clinical activity of 1L atezolizumab + bevacizumab in a phase Ib study in hepatocellular carcinoma (HCC).”
The company expects to present updated data at a future medical conference.
“Hepatocellular carcinoma is an aggressive cancer with limited treatment options and a major cause of cancer deaths worldwide,” Sandra Horning, MD, said in a press release. Horning is chief medical officer and head of Global Product Development at Genentech. “Preliminary data from the combination of Tecentriq and Avastin in this disease are promising and we look forward to working with health authorities to make this potential treatment regimen available to people with hepatocellular carcinoma as soon as possible.”
Earlier this year, Genentech launched the IMbrave150 Phase 3 trial (NCT03434379) to continue testing Tecentriq and Avastin in previously untreated unresectable or metastatic hepatocellular carcinoma.
Currently recruiting patients, the trial will compare the combination treatment with Nexavar (sorafenib), a therapy already approved for first-line treatment of advanced liver cancers. For additional information on the trial, click here.