Multidisciplinary findings across the field of hepatocellular carcinoma will be showcased at the 11th International Liver Cancer Association Annual Conference on September 15 to 17 in Seoul, South Korea. Abstracts already under discussion at this year’s ILCA conference include pivotal research on VGEF inhibitors, immunotherapy regimens, and biomarkers.
Richard Finn, MD
Multidisciplinary findings across the field of hepatocellular carcinoma will be showcased at the 11th International Liver Cancer Association (ILCA) Annual Conference on September 15 to 17 in Seoul, South Korea. Abstracts already under discussion at this year’s ILCA conference include pivotal research on VGEF inhibitors, immunotherapy regimens, and biomarkers.
“[At ILCA] we not only cover all of the clinical disciplines involved in the management of liver cancer but the presentations at this meeting include surgical oncology, transplant surgery, hepatology, interventional radiology, pathology, as well as medical oncology,” explained Richard Finn, MD, an associate professor of medicine at David Geffen School of Medicine at University of California, Los Angeles. “One of the most important things the audience will take away from the meeting is the latest data in not only systemic treatments, but also the role of treating hepatitis C in the setting of advanced and early-stage liver cancer. They will go home with some practice-changing observations.”
In an interview withTargeted Oncology, Finn, chair of the plenary session at the ILCA meeting, highlighted the abstracts that are most anticipated among the liver cancer community.This study compared frontline lenvatinib (Lenvima) with sorafenib (Nexavar) in patients with unresectable HCC. Prior phase III results presented at the 2017 ASCO Annual Meeting demonstrated that lenvatinib is non-inferior in overall survival (OS) and achieves significant improvements in progression-free survival (PFS), time to progression, and objective response rate (ORR) compared with sorafenib.
In this randomized, open-label study, 954 patients were enrolled to receive lenvatinib (n = 478) or sorafenib (n = 476) at 400 mg twice daily. The median OS was 13.6 months versus 12.3 months respectively (HR, 0.92; 95%; CI, 0.79-1.06). The PFS was 7.4 months for lenvatinib compared with 3.7 months with sorafenib (HR, 0.66; 95%; CI, 0.57-0.77;P<0.00001).1,2
“The positive data with lenvatinib being non-inferior to sorafenib is now being disseminated, but we’re still waiting for regulatory approval,” Finn states.
Since sorafenib is currently the only approved regimen in the frontline setting of the liver cancer space, many are interested in lenvatinib and its future in the field. Moreover, researchers continue to investigate the use of biomarkers to determine the most appropriate patients to receive lenvatinib over sorafenib, as well as how to best sequence these agents.STORM was a large, phase III study investigating the use of sorafenib after curative resection in patients at early stages of liver cancer. Overall, sorafenib did not improve clinical outcomes; however, because of its design as an adjuvant trial, there was an opportunity for investigators to evaluate the tissue for a biomarker analysis.
“When we talk about liver tumor characteristics, we don't stratify patients based on biomarkers for any selective factors. That is different from other malignancies where biomarkers have had a major impact in patient care, such asEGFRmutations in lung cancer orHER2amplification in breast cancer,” states Finn.
Tumor samples from 188 resected HCC tumors were investigated in this trial having been treated with sorafenib (n = 83) or placebo (n = 105). Prognostic and predictive biomarkers were analyzed by gene expression, targeted exome sequencing of 18 mutational drivers, assessment of activation of MAPK signaling, and angiogenesis.
Regarding prognostic variables for recurrence-free survival, positive hepatocyte pERK staining (HR, 2.41; 95% CI, 1.21-4.80;P= 0.012) and microvascular invasion were independent prognostic factors. This study did not identify candidate biomarkers predicting recurrence prevention to sorafenib.
Results showed that no mutation, gene amplification or previously supposed signature predicted recurrence or prevention with sorafenib.3
“This is a very exciting abstract, as we are still attempting to figure out how to link tumor biology to response in novel therapeutics in liver cancer,” explains Finn.In this study, patients with locally advanced HCC showed no significant differences in overall survival between selective internal radiation therapy (SIRT) using 90yttrium (Y-90) resin microspheres versus oral sorafenib treatment.
Although daily sorafenib is recommended for patients with advanced HCC, alternative treatments demonstrating an increase in the safety profile continue to be investigated. The tumor response rate was statistically significant among patients who received SIRT (16.5%) than those who received sorafenib (1.7%).
Additionally, there were significantly fewer adverse events (AEs) with SIRT than with sorafenib. Fewer patients on the SIRT arm had more than 1 AE compared with the sorafenib arm at 60.0% versus 84.6%, respectively. Similarly, fewer patients had grade 3 AEs in the SIRT arm compared with sorafenib, at 27.7% versus 50.6%, respectively.
This multicenter trial enrolled 360 patients and demonstrated a median OS of 8.84 months in the SIRT arm and 10.02 months in the sorafenib arm (HR, 1.13; 95% CI, 0.88-1.42). PFS was 6.01 months and 5.06 months in the SIRT and sorafenib arms (HR, 0.88; 95% CI, 0.701.10).4
“This is an area of great interest and we look forward to seeing the results of the study,” states Finn.