FDA Approves Atezolizumab Combo for Unresectable or Metastatic Hepatocellular Carcinoma

May 29, 2020

“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.”

The FDA has granted approval to atezolizumab (Tecentriq) in combination with bevacizumab (Avastin) as treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not had a prior systemic therapy, announced Genentech.1

This approval was based on findings from the phase 3 IMbrave150 clinical trial, where the combination reduced the risk of death by 42% (HR, 0.58; 95% CI, 0.42-0.79; P = .0006) compared with sorafenib (Nexavar) alone. The combination also reduced the worsening of disease or death by 41% (HR, 0.59; 95% CI, 0.47-0.76; P <.0001) compared with sorafenib.

IMbrave150 was the first study to demonstrate an improved overall survival (OS) and progression-free survival (PFS) with immunotherapy in patients with unresectable or metastatic 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 and director of the Signal Transduction and Therapeutics Program at the UCLA Jonsson Comprehensive Cancer Center, in a press release. “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.”

Serious adverse reactions of grade 3 or 4 in severity occurred in 38% of patients in the combination arm, with the most frequent serious adverse reaction noted as bleeding in the gastrointestinal tract, infections, and fever.

Updated findings for the IMbrave150 trial were presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program. These data resulted in a statistically significant and clinically meaningful improvement in both OS and PFS with the combination versus sorafenib in this patient population. Complete responses (CRs) were achieved regardless of poor prognostic factors or etiology.2

Patients were randomized to receive either the combination (n = 336) or sorafenib (n = 165). After a median follow-up of 8.6 months, the OS HR was 0.58 (95% CI, 0.42-0.79; P = .0006). The PFS HR was 0.59 (95% CI, 0.47-0.76; P <.0001). The objective response rate (ORR) per independent review facility (IRF) RECIST 1.1 criteria was 27% with the combination versus 12% with sorafenib (P <.0001), and the ORR by IRF HCC modified RECIST (mRECIST) criteria was 33% for the combination versus 13% for sorafenib (P <.0001).

The median time to response was 2.8 months (range, 1.2-11.3) with the combination versus 3.3 months with sorafenib (range, 1.2-7.2). CR per IRF RECIST 1.1 was achieved in 18 patients from the combination arm versus 0 in the sorafenib arm.

Patients with unresectable HCC who were treatment-naïve were enrolled to the IMbrave150 study, where they were randomized 2:1 to receive either the combination regimen with 1200 mg intravenously every 3 weeks with bevacizumab at 15 mg/kg intravenously every 3 weeks, or sorafenib along at 400 mg until unacceptable toxicity or loss of clinical benefit according to the investigator.

IMbrave150 is a global multicenter, open-label study. The co primary end points were OS and PFS by IRF-assessed RECIST 1.1. Secondary end points included IRF ORR per RECIST 1.1 and IRF ORR per HCC mRECIST.

To be eligible for the study, patients had to have locally advanced or metastatic and/or unresectable HCC, no prior systemic therapy, had ≥1 measurable lesion, an ECOG performance status of 0 or 1, adequate hematologic and end-organ function, and Child-Pugh class A disease. Patients with leptomeningeal disease, active or history of autoimmune disease/immune deficiency, or a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan were ineligible to enroll. Patients were also not eligible if they had active tuberculosis, history of cancer other than HCC within 5 years prior to screening; known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC, and a history of hepatic encephalopathy.

“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,” stated Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, in the 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.”

References

  1. FDA Approves Genentech’s Tecentriq in Combination With Avastin for People With the Most Common Form of Liver Cancer. Published May 29, 2020. Accessed May 29, 2020. https://bit.ly/2Aneztc.
  2. Complete responses (CR) in patients receiving atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in IMbrave150: A phase III clinical trial for unresectable hepatocellular carcinoma (HCC). Presented at the 2020 ASCO Virtual Scientific Program; May 29, 2020. Abstract 4596.