FDA Grants Breakthrough Device Status to Elecsys GALAD Score for HCC

Amit Singal, MD

The FDA has granted a breakthrough device designation to the Elecsys GALAD score, an algorithmic score designed to aid in the diagnosis of early-stage hepatocellular carcinoma (HCC).

If approved, the Elecsys GALAD score, which is manufactured by Roche, would be the first GALAD score for use in In Vitro Diagnostics. The score is part of the Roche Diagnostics Liver Indication Program, which aims to improve diagnostic workflows throughout chronic liver disease management.

The Elecsys GALAD score would be used in combination with ultrasound and could provide clinicians with more accurate information at an earlier stage of disease with a minimally invasive approach, potentially improving patient outcomes, while possibly becoming more affordable to healthcare systems, Roche stated in a press release.

"HCC is the fourth leading cause of cancer-related death worldwide, with the highest burden of disease in East Asia and Africa,” Amit Singal, MD, medical director of the Liver Tumor Program, and clinical chief of Pathology at UT Southwestern Medical Center, stated in the press release. “This high mortality is largely driven by most patients being detected at a late stage, when curative therapies are no longer possible. Therefore, improving early HCC detection is a critical area of need."

The GALAD score was pioneered by Professor Philip Johnson, MD, FRCP, deputy director of North West Cancer Research Centre, professor in translational oncology at University of Liverpool, and colleagues. It is a serum biomarker-based model that predicts the probability of having HCC in patients who have chronic liver disease. This is done by combining gender and age with assay results for alpha1-fetoprotein (AFP), AFP-L3, and PIVKA-II, which are all biomarkers associated with HCC, to predict a more accurate picture of disease risk.

Elevated levels of AFP, for example, also warrant use for ramucirumab (Cyramza) in the second-line HCC setting. In May 2019, the FDA approved single-agent ramucirumab for patients with HCC who have an AFP of ≥400 ng/mL and have been previously treated with sorafenib (Nexavar).

The approval was based on findings from the international, double-blind, placebo-controlled, multicenter phase III REACH-2 trial, in which the median overall survival (OS) was 8.5 months with ramucirumab compared with 7.3 months with placebo (HR, 0.71; 95% CI, 0.53-0.95, P = .020) in patients who experienced progression on or intolerance to frontline sorafenib.²

Results of REACH-2 also showed that the survival benefit was consistent across all prespecified subgroups. The 12- and 18-month OS rates both favored ramucirumab at 36.8% versus 30.3% and 24.5% versus 11.3%, respectively. Moreover, the median progression-free survival (PFS) was 2.8 months with ramucirumab versus 1.6 months with placebo (HR, 0.452; 95% CI, 0.339-0.603; P <.0001).

In the previously reported REACH trial of patients with advanced HCC, treatment with ramucirumab did not significantly improve OS in the intention-to-treat population.^3,4 However, a prespecified subgroup analysis revealed a significant survival benefit in patients with AFP levels ≥400 ng/mL. These data provided a rationale for a follow-up trial to evaluate ramucirumab in patients with HCC associated with elevated AFP.

"We are excited about FDA’s recognition of the potential clinical benefit the Elecsys GALAD score could bring in diagnosing hepatocellular cancer at an early stage," Thomas Schinecker, CEO of Roche Diagnostics, stated in the press release. "The combination of blood-based biomarkers with clinical algorithms has the potential to significantly reduce mortality of HCC patients as they can receive a more timely diagnosis and treatment."

References

1. FDA grants breakthrough device designation for Roche's Elecsys GALAD score to support earlier diagnosis of hepatocellular carcinoma [news release]: Basel, Switzerland. Roche. Published March 4, 2020. https://bit.ly/2PLLY5H. Accessed March 4, 2020.
2. Zhu AX, Kang Y-K, Yen C-J, et al. REACH-2: a randomized, double-blind, placebo-controlled phase 3 study of ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated baseline alpha-fetoprotein (AFP) following first-line sorafenib. J Clin Oncol. 2018;36 (suppl; abstr 4003). doi: 10.1200/JCO.2018.36.15_suppl.4003
3. Zhu AX, Ryoo B-Y, Yen C-J, et al. Ramucirumab (RAM) as second-line treatment in patients (pts) with advanced hepatocellular carcinoma (HCC): analysis of patients with elevated α-fetoprotein (AFP) from the randomized phase III REACH study. J Clin Oncol. 2015;33(suppl_3; abstr 232). doi: 10.1200/jco.2015.33.3_suppl.232
4. Zhu AX, Park JO, Ryoo B-Y, et al. Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2015; 16(7):859-870. doi: 10.1016/S1470-2045(15)00050-9