Tecentriq (atezolizumab), in combination with Avastin (bevacizumab), has been recommended for approval in the European Union as a first-line treatment for adults with advanced hepatocellular carcinoma (HCC), the most common form of liver cancer.
The recommendation was made by the Committee for Medicinal Products for Human Use (CHMP), an arm of the European Medicines Agency. The CHMP’s recommendations are generally accepted by the European Commission, which makes the final decisions.
“Today’s recommendation by the CHMP is a major step towards bringing Tecentriq in combination with Avastin to people in Europe who suffer from advanced or [inoperable] hepatocellular carcinoma,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in a press release.
Genentech, a subsidiary of Roche, is the developer of both Tecentriq and Avastin.
“This represents an important milestone in a deadly malignancy and is part of our long-term commitment to improve the lives of people with various types and stages of liver disease,” Garraway added.
The CHMP’s positive opinion follows the combo’s approval in the U.S. for the same indication. The U.S. Food and Drug Administration‘s May 2020 approval made the combo the first and only immunotherapy regimen available in the United States for people with untreated, advanced HCC.
Tecentriq is an immune checkpoint inhibitor that works by blocking PD-L1, a protein used by cancer cells to evade immune system attack. Avastin, meanwhile, limits the blood supply of tumors, restricting their growth and spread. It blocks VEGF-A, a protein required for the growth of new blood vessels in tumors.
The CHMP’s positive opinion was based on data from the ongoing IMbrave150 Phase 3 trial (NCT03434379), which is investigating whether the Tecentriq-Avastin combo is more effective than standard treatment with Nexavar (sorafenib) in people with locally advanced or metastatic HCC who had never received any form of cancer therapy.
A total of 501 participants were randomly assigned to receive either the Tecentriq-Avastin combo, administered directly into the vein every three weeks, or oral Nexavar twice a day. Treatment continued until unacceptable toxicity or loss of clinical benefit, as determined by the investigators.
The trial’s main goals were to assess whether the combination therapy was superior to Nexavar at prolonging patients’ overall survival and the time they lived without signs of disease progression. Secondary goals included the proportion of participants responding to treatment, quality of life, and safety measures.
Results from IMbrave150’s first pre-defined analysis showed that the trial met both its main and several secondary goals.
Compared with Nexavar, the combo significantly reduced the risk of death by 42%, and the risk of disease progression or death by 41%. In addition, a larger proportion of patients on the combo responded to treatment, compared with those receiving Nexavar (27.3% vs. 11.9%).
Additional data, presented at the American Society of Clinical Oncology (ASCO) 2020 Gastrointestinal Cancers Symposium, showed that the combination therapy also delayed declines in patient-reported overall quality of life.
The safety of Tecentriq-Avastin was consistent with the known profiles of each therapy, with no new safety concerns identified. About half of the patients in both groups reported severe to life-threatening adverse events, and the most commonly reported serious adverse events included gastrointestinal tract bleeds, infections, and fever.
This was the first trial to show evidence of superiority of a cancer immunotherapy regimen over standard treatment in patients with advanced or inoperable HCC.
“After more than a decade of therapeutic stagnation, the results of the IMbrave150 study are likely to change the way we treat patients with liver cancer who are diagnosed at or reach the advanced stage,” said Bruno Sangro, the director of the liver unit and coordinator of the hepato-pancreato-biliary oncology area at Clinica Universidad de Navarra, in Spain.
“The data from the study showed that the combination of Tecentriq and Avastin results in longer survival with better quality of life than any current choice of tyrosine kinase inhibitor and, for a large subset of patients, is able to induce deep, durable and sometimes complete tumour remissions,” Sangro added.
Notably, a study presented at the 2020 ASCO Virtual Scientific Program, also held online this year, showed that the Tecentriq-Avastin combo is likely more effective than other approved therapies for inoperable HCC.
The systematic review compared the effectiveness data of the combo in IMbrave150 with that of Lenvima (lenvatinib) in the REFLECT Phase 3 study (NCT01761266), and with that of Opdivo (nivolumab) in the CheckMate-459 Phase 3 trial (NCT02576509).
Results indicated the Tecentriq-Avastin combo had a 93.7% chance of being superior to Lenvima, and a 90.3% chance of being more effective than Opdivo, at prolonging patients’ lives.
The combination therapy also was found to be likely superior to Lenvima (61.5% chance) and Opdivo (85.5% chance) at prolonging the time patients lived without showing signs of disease progression or death.
Genentech also is exploring the therapeutic potential of Tecentriq, either alone or in combination with other medications, across several types of lung, genitourinary (urinary system and male reproductive system), skin, breast, gastrointestinal, gynecological, and head and neck cancers.