The U.S. Food and Drug Administration (FDA) has approved Tecentriq (atezolizumab) in combination with Avastin (bevacizumab) for the treatment of newly diagnosed patients with advanced hepatocellular carcinoma (HCC), the most common form of liver cancer.

Genentech, a Roche subsidiary developing Tecentriq, submitted a supplemental biologics license application to the FDA earlier this year requesting approval for this indication. With the new approval, the combination therapy of Tecentriq-Avastin has become the first and only FDA-approved cancer immunotherapy regimen for untreated patients with advanced HCC.

“We’re excited that today’s approval of Tecentriq in combination with Avastin for unresectable or metastatic hepatocellular carcinoma brings a cancer immunotherapy option to people with this aggressive form of liver cancer,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in a press release.

“The application was reviewed under the FDA’s Real-Time Oncology Review pilot and Project Orbis initiative, helping to bring this new treatment option rapidly to patients in the United States and around the world,” Garraway said.

The FDA’s Project Orbis was created to allow simultaneous submission and review of cancer medications among international regulatory partners. The initiative aims to allow cancer patients to have access to life-saving medications in countries where their regulatory submissions may be delayed. To date, simultaneous drug applications have been submitted and reviewed by regulatory agencies in the U.S., Australia, Canada, and Singapore, under this initiative.

The rapid review and approval of the Tecentriq-Avastin combo was also facilitated by the FDA’s Real-Time Oncology Review pilot program, which was created to improve the efficiency of the review process, so that safe and effective medications may be available to patients as soon as possible.

Tecentriq belongs to a class of immunotherapies known as immune checkpoint inhibitors that work by blocking proteins used by cancer cells to evade immune responses. Tecentriq specifically blocks PD-L1, which is produced by cancer cells and dampens immune responses when bound to the PD-1 receptor on immune cells.

Avastin, also developed by Genentech, belongs to a class anti-angiogenic medications that are designed to limit the blood supply of tumors in order to restrict their growth.

The FDA’s decision to approve the Tecentriq-Avastin combo was based on data from the IMbrave150 Phase 3 trial (NCT03434379).

IMbrave150 was designed to investigate whether first-line therapy with the Tecentriq-Avastin combo would be able to prolong patients’ survival beyond that attained with standard treatment with oral Nexavar (sorafenib).

The trial enrolled 501 patients with locally advanced or metastatic HCC who had never received any form of cancer therapy. They were randomly assigned to receive the Tecentriq-Avastin combo, administered intravenously, on the first day of each 21-day cycle, or oral Nexavar twice a day.

Treatment lasted until patients showed signs of unacceptable toxicity or until it lost its clinical benefit, as determined by the investigators.

Findings from IMbrave150 recently published in The New England Journal of Medicine showed the Tecentriq-Avastin combo reduced the risk of death by 42%, and the risk of disease progression or death by 41% compared with Nexavar.

Treatment response rates were also higher among patients receiving the Tecentriq-Avastin combo therapy (27.3%) compared to those treated with Nexavar (11.9%).

Serious adverse reactions were observed in approximately a third (38%) of the patients treated with the combination therapy. The most common serious adverse reactions reported during the trial 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.

“The results of the IMbrave150 study are really transformative for patients with advanced liver cancer, one of the few cancers with a rising death rate and limited options in the first-line setting,”  said Richard Finn, MD, professor of medicine at the David Geffen School of Medicine at UCLA.

“For the first-time we have a regimen that markedly improves survival over sorafenib, the standard of care for first-line hepatocellular carcinoma since 2007, and offers patients the opportunity for improved disease control with a favorable tolerability profile,” added Finn, who is also director of the signal transduction and therapeutics program at the UCLA Jonsson Comprehensive Cancer Center.

These findings were also supported by data from a systematic review and meta-analysis recently presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program, in the poster “Clinical value of atezolizumab + bevacizumab for first-line unresectable hepatocellular carcinoma (HCC): A network meta-analysis.”

The analysis, which aimed to compare the efficacy of the Tecentriq-Avastin combo therapy to that of other approved therapies for inoperable HCC, was based on data from nine clinical trials, including IMbrave150, REFLECT (NCT01761266), and CheckMate-459 (NCT02576509).

Statistical analyses indicated the Tecentriq-Avastin combo had a 93.7% chance of being superior to Lenvima (lenvatinib) and a 90.3% of being superior to Opdivo (nivolumab) at prolonging patients’ lives.

The combination therapy was also 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.

Altogether, these findings suggested the Tecentriq-Avastin combo provided greater benefits in terms of overall survival and disease progression control to patients with inoperable HCC, compared to other approved therapies.

Genentech is also exploring the therapeutic potential of Tecentriq, both alone and in combination with other medications, for other types of cancers, including lung, genitourinary, skin, breast, gastrointestinal, gynecological, and head and neck cancers.

The company is offering patient assistance programs for those taking Tecentriq through its Access Solutions program. More information about the program is available here.