New standard treatment for advanced liver cancer

SAN ANTONIO — The addition of radiotherapy to systemic therapy significantly improved overall survival (OS) in advanced liver cancer, according to a randomized trial reported here.

Median OS improved from 12.3 months with the targeted agent sorafenib (Nexavar) to 15.8 months with stereotactic body radiation therapy (SBRT) followed by sorafenib. All landmark survival analyzes from 6 months to 24 months favored the SBRT arm, with increasing magnitude of benefit over time.

“In patients with advanced hepatocellular carcinoma, use of SBRT before sorafenib improved overall survival, progression-free survival (PFS), and time to progression (TTP) compared with sorafenib alone. but there was no worrying increase in adverse events,” reports Laura Dawson. Physician at Princess Margaret Cancer Center in Toronto. American Society for Radiation Oncology (ASTRO) Annual Meeting.

“Considering the univariate and multivariate analyses, this study adds to the evolving data on the benefits of radiation in the treatment of patients with hepatocellular carcinoma, and adds SBRT to the toolkit of standard treatment options for patients with metastatic cancer.” In addition, and perhaps the greatest benefit, is in patients with vascular invasion, a particularly difficult patient population to treat,” she said. “We hope this will help raise awareness of the importance of hepatocellular carcinoma and the great benefits SBRT can add to the treatment of these patients.”

At an ASTRO press briefing, Karin Goodman, M.D., Ph.D., of the Icahn School of Medicine in Mount Sinai, New York City, said the results could provide a new standard of care for patients with difficult-to-treat conditions.

‘This is one of the most important studies published in many years in terms of practice-changing results,’ said Goodman. macrovascular invasion showed a significant improvement in overall survival. Improved. Call this your standard of care. ”

global burden of disease

In presenting key results from the NRG/RTOG1112 trial, Dawson noted that HCC remains the leading cause of cancer death and its incidence is rising in North America. Systemic therapy is the standard treatment for HCC that is unresectable or unsuitable for thermal ablation or local therapy. When NRG/RTOG1112 was initiated, the multikinase inhibitor sorafenib was the standard systemic therapy, Improved median OS 7.9 to 10.7 months in placebo-controlled trials.

Patients with macrovascular involvement benefit less from systemic therapy and have worse outcomes, continued Dawson.

“Integrating radiation strategies into the treatment of HCC patients has been studied for decades, primarily in single-arm studies,” she said. had a longer-than-expected survival rate.There were several randomized trials conducted primarily with yttrium-90 radioembolization of the hepatic artery, but they did not show an improvement in survival. Is not.”

NRG/RTOG1112 tested the hypothesis that sorafenib following SBRT improves OS compared with single-agent sorafenib in advanced HCC. PFS and TTP were the key secondary endpoints. Eligible patients had locally advanced HCC that was unsuitable for surgery, radiofrequency ablation, or transarterial chemoembolization, was refractory, or subsequently relapsed. Patients had a maximum tumor burden of 20 cm or less, and any degree of vascular invasion was tolerated.

Patients were randomized to receive standard daily doses of sorafenib or SBRT followed by a modified dosing schedule of sorafenib. The median follow-up was 13.2 months for the patient, including her 33.7 months for the patient alive at the end of the study.

Key Findings, Implications

Primary analysis showed that initiation of treatment with SBRT was associated with a 23% reduction in survival hazard compared with single-agent sorafenib (95% CI 0.59-1.01, P.= 0.055). The survival improvement in favor of the SBRT arm he appeared within 6 months (88% vs 71%) and was evident by 24 months (33% vs 23%).

Multivariate analysis confirmed that the combination of sorafenib and SBRT significantly reduced survival hazard (HR 0.72, 95% CI 0.52-0.99, P.=0.042). Confirming the large body of existing data, large vessel involvement was a significant negative predictor of survival (HR 2.34, 95% CI 1.63-3.34, P.<0.0001).

Analysis of secondary endpoints showed that the addition of SBRT significantly improved median PFS from 5.5 months to 9.2 months with sorafenib alone (HR 0.55, 95% CI 0.40-0.75 , P.= 0.0001). Median TTP was 9.5 months with sorafenib monotherapy and increased to 18.5 months with SBRT followed by sorafenib (HR 0.69, 95% CI 0.48-0.99, P.= 0.034).

The frequency of grade 3 or higher adverse events (AEs) was not increased with the addition of SBRT (75%) versus single-agent sorafenib (74%). Gastrointestinal bleeding occurred in 6% of patients in the sorafenib group and 4% in the SBRT group.

Although single-agent sorafenib is no longer the standard of care for advanced HCC, the findings remain relevant in the current clinical practice setting, Dawson and Goodman said. MedPage Today on mail.

“We believe these results are applicable to all patients receiving approved TKIs. [tyrosine kinase inhibitors] Mr Dawson said: [MVI]However, the exact benefits and optimal sequence of radiotherapy and immunotherapy are unknown, and we hope that this will be the focus of future clinical trials.”